International Journal of

Head and Neck Pathology and Radiology 2011

Guest Editors: Neil S. Norton, Preetha P. Kanjirath, Pilar Hita-Iglesias, and Paul C. Edwards Head and Neck Pathology and Radiology 2011 International Journal of Dentistry

Head and Neck Pathology and Radiology 2011

Guest Editors: Neil S. Norton, Preetha P. Kanjirath, Pilar Hita-Iglesias, and Paul C. Edwards Copyright © 2012 Hindawi Publishing Corporation. All rights reserved.

This is a special issue published in “International Journal of Dentistry.” All articles are open access articles distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Editorial Board

Ali Abdalla, Egypt James K. Hartsfield, USA Chikahiro Ohkubo, Japan Yahya Ac¸il, Germany Yumiko Hosoya, Japan Athena Papas, USA Jasim M. Albandar, USA Saso Ivanovski, Australia Patricia Pereira, USA Eiichiro Ariji, Japan Chia-Tze Kao, Taiwan Roberta Pileggi, USA Manal Awad, UAE Elizabeth Kay, UK A. B. M. Rabie, Hong Kong Ashraf F. Ayoub, UK Heidrun Kjellberg, Sweden Michael E. Razzoog, USA Silvana Barros, USA Kristin Klock, Norway AndreReis,Brazil´ Sema Belli, Turkey Kee-Yeon Kum, Republic of Korea Stephen Richmond, UK Marilia Buzalaf, Brazil Manuel Lagravere, Canada George E. Romanos, USA Giuseppina Campisi, Italy Daniel M. Laskin, USA Kamran Safavi, USA Francesco Carinci, Italy Claudio R. Leles, Brazil Tuula Salo, Finland Lim K. Cheung, Hong Kong Louis M. Lin, USA Gilberto Sammartino, Italy BrianW.Darvell,Kuwait A. D. Loguercio, Brazil Robin Seymour, UK Hugo De Bruyn, Belgium Tommaso Lombardi, Switzerland Timo Sorsa, Finland Dong M. Deng, The Netherlands Martin Lorenzoni, Austria Gianrico Spagnuolo, Italy Shinn-Jyh Ding, Taiwan Adriano Loyola, Brazil Andreas Stavropoulos, Denmark J. D. Eick, USA Maria Machado, Brazil Dimitris N. Tatakis, USA Annika Ekestubbe, Sweden Jukka H. Meurman, Finland Shigeru Uno, Japan Carla Evans, USA Hendrik Meyer-Luckel, Germany Jacques Vanobbergen, Belgium Vincent Everts, The Netherlands Konstantinos Michalakis, Greece Marcos Vargas, USA Stefano Fedele, UK Masashi Miyazaki, Japan Ahmad Waseem, UK G.NogueiraFilho,Canada Yasuhiro Morimoto, Japan Izzet Yavuz, Turkey Roland Frankenberger, Germany Carlos A. Munoz-Viveros, USA Cynthia Yiu, Hong Kong Gerald Glickman, USA Hiroshi Murata, Japan Li-wu Zheng, Hong Kong Valeria V. Gordan, USA Ravindra Nanda, USA Qiang Zhu, USA Rosa H. Grande, Brazil Toru Nikaido, Japan Spiros Zinelis, Greece Yoshitaka Hara, Japan Joseph Nissan, Israel Contents

Head and Neck Pathology and Radiology 2011, Neil S. Norton, Preetha P. Kanjirath, Pilar Hita-Iglesias, and Paul C. Edwards Volume 2012, Article ID 320319, 1 page

Cone-Beam Computed Tomography and Radiographs in Dentistry: Aspects Related to Radiation Dose, Diego Coelho Lorenzoni, Ana Maria Bolognese, Daniela Gamba Garib, Fabio Ribeiro Guedes, and Eduardo Franzotti Sant’Anna Volume 2012, Article ID 813768, 10 pages

Supernumerary Teeth in Indian Children: A Survey of 300 Cases, Amita Sharma and Varun Pratap Singh Volume 2012, Article ID 745265, 5 pages

Oral as It Relates to HPV Infection: A Review, L. Feller and J. Lemmer Volume 2012, Article ID 540561, 7 pages

Technical Considerations in Rehabilitation of an Edentulous Total Glossectomy Patient, Pravin Bhirangi, Priyanka Somani, K. P. Dholam, and Gurmeet Bachher Volume 2012, Article ID 125036, 4 pages

Cell Transformation and the Evolution of a Field of Precancerization As It Relates to Oral Leukoplakia, L. Feller and J. Lemmer Volume 2011, Article ID 321750, 5 pages Hindawi Publishing Corporation International Journal of Dentistry Volume 2012, Article ID 320319, 1 page doi:10.1155/2012/320319

Editorial Head and Neck Pathology and Radiology 2011

Neil S. Norton,1 Preetha P. Kanjirath,2 Pilar Hita-Iglesias,3 and Paul C. Edwards4

1 Department of Oral Biology, School of Dentistry, Creighton University, Omaha, NE 68178, USA 2 Preclinical Program, College of Dental Medicine-Illinois, Midwestern University, 555-31st Street, 102 Redwood Hall, Downers Grove, IL 60515, USA 3 Department of Periodontics and Oral Medicine, School of Dentistry, University of Michigan, Ann Arbor, MI 48109, USA 4 Oral and Maxillofacial , School of Dentistry, University of Michigan, Ann Arbor, MI 48109, USA

Correspondence should be addressed to Neil S. Norton, [email protected]

Received 11 December 2012; Accepted 11 December 2012

Copyright © 2012 Neil S. Norton et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Beyond an examination of the dentition and surrounding Acknowledgments periodontal tissues, one of the most important tasks of the dental clinician is the accurate diagnosis and management of This special issue on head and neck pathology and radiology patients with nontooth-related conditions of the head and would not be possible without the invaluable work of my fel- ff neck. For patients with these conditions, it is imperative that low guest editors. Thus, I would like to o er my sincere the dental clinician performs a comprehensive evaluation thanks and appreciation to Dr. P.P.Kanjirath, from Midwest- and assessment on patients to increase the potential for a suc- ern University, USA, Dr. P. H.-Igelsias, and Dr. P. C. Edwards cessful outcome. The skills of a myriad of specialists will be from the University of Michigan at Ann Arbor, USA. Each involved, including those in oral and maxillofacial pathology, of them worked tirelessly on this project. Additionally, I ff radiology, oral medicine, head and neck anatomy, and the would like to o er my thanks to the authors that contributed primary care provider. their research to this special issue. Finally, this special issue In this special issue dedicated to head and neck pathology would not be possible without the numerous reviewers that ff ff and radiology, the manuscripts selected for publication fur- selflessly o ered their expertise—to them I o er my sincere ther demonstrate the significance of the relationship des- gratitude. On behalf of Drs. P. P. Kanjirath, P. H.-Igelsias, P. cribed between the specialists and primary care provider. The C. Edwards and myself, it is our sincere hope that you enjoy article by D. C. Lorenzoni et al. highlights radiology and this special issue and find each of the articles as fascinating discusses the radiation doses that are associated with plain and instructive as we do. radiographs, cone beam computed tomography (CBCT), Neil S. Norton and conventional computed tomography (CT), placing a Preetha P. Kanjirath special emphasis on orthodontics. A. Sharma and V. P. Singh Pilar Hita-Iglesias thoroughly summarize a study detecting supernumerary Paul C. Edwards teeth in Indian children in 300 cases using clinical and radio- graphic examination. In one of their two articles in this special issue, L. Feller and J. Lemmer provide an exten- sive review on oral leukoplakia and its relationship to human papillomavirus (HPV). P. Bhirangi et al. elaborate on the technical steps for the prosthetic rehabilitation of an eden- tulous glossectomy patient. In the other article, L. Feller and J. Lemmer critically review cell transformation and the evo- lution of a field of precancerization as it relates to oral leuko- plakia. Hindawi Publishing Corporation International Journal of Dentistry Volume 2012, Article ID 813768, 10 pages doi:10.1155/2012/813768

Review Article Cone-Beam Computed Tomography and Radiographs in Dentistry: Aspects Related to Radiation Dose

Diego Coelho Lorenzoni,1 Ana Maria Bolognese,1 Daniela Gamba Garib,2 Fabio Ribeiro Guedes,3 and Eduardo Franzotti Sant’Anna1

1 Department of Orthodontics, Federal University of Rio de Janeiro Dental School, Avenida Professor Rodolpho de Paulo Rocco, Ilha do Fundao˜ 21941-590, Rio de Janeiro, RJ, Brazil 2 Department of Orthodontics, Bauru Dental School and Hospital of Rehabilitation of Craniofacial Anomalies, Universtity of Sao˜ Paulo, 17012-101 Bauru, SP, Brazil 3 Department of Dental Radiology, Federal University of Rio de Janeiro Dental School, 21941-590 Rio de Janeiro, RJ, Brazil

Correspondence should be addressed to Eduardo Franzotti Sant’Anna, [email protected]

Received 14 July 2011; Revised 19 September 2011; Accepted 31 January 2012

Academic Editor: Neil S. Norton

Copyright © 2012 Diego Coelho Lorenzoni et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Introduction. The aim of this study was to discuss the radiation doses associated with plain radiographs, cone-beam computed tomography (CBCT), and conventional computed tomography (CT) in dentistry, with a special focus on orthodontics. Methods.A systematic search for articles was realized by MEDLINE from 1997–March 2011. Results. Twenty-seven articles met the established criteria. The data of these papers were grouped in a table and discussed. Conclusions. Increases in kV, mA, exposure time, and field of view (FOV) increase the radiation dose. The dose for CT is greater than other modalities. When the full-mouth series (FMX) is performed with round collimation, the orthodontic radiographs transmit higher dose than most of the large FOV CBCT, but it can be reduced if used rectangular collimation, showing lower effective dose than large FOV CBCT. Despite the image quality, the CBCT does not replace the FMX. In addition to the radiation dose, image quality and diagnostic needs should be strongly taken into account.

1. Introduction overlap and distortion. With the introduction of cone-beam computed tomography (CBCT), there was much interest The high prevalence and increase in the number of children in the technology due to its advantages: improved image receiving orthodontic care [1] bring up an important issue: quality, three-dimensional reconstruction, a 1 : 1 ratio that the use of ionizing radiation for diagnosis also increases the allowed reliable measurements, the possibility for craniofa- potential impact on public health [2].Theseconcernsexist cial visualization, and lower radiation doses compared to because of the ability of X-rays to induce mutations in DNA, traditional CT. thereby increasing the risk of cancer [3]. Moreover, children However, it is necessary to monitor the radiation doses may express increased susceptibility to environmental haz- involved in these exams. Some concepts are relevant for ards, chronic infection and inflammation, dietary factors, this understanding, such as the methodology employed in and long-term medication due to differences in the uptake, research studies within the field. The majority of these metabolism, and excretion of potential mutagens [4]anda studies use human head and neck phantoms built with recent study has suggested a relationship between exposure tissues that mimic human tissues in regard to layers and to dental radiographs and a greater risk of thyroid cancer [5]. radiation absorption. In some models, human skeletons are During the last century, dental diagnostic imaging was used [6]. The phantom is made in the form of detachable dominated by radiographs, which are two-dimensional rep- cross-sections with apertures created for the placement of resentations of three-dimensional structures, with associated dosimeters in the regions of interest. Many of these locations 2 International Journal of Dentistry would be unfeasible in vivo. The dosimeters measure the ab- was “radiation dose,” combined with 31 descriptors to res- sorbed dose in each region/tissue. trict it to dentistry (Figure 1). The bibliographies of the The description of the radiation dose transmitted to selected articles were analyzed in search of research that was the patient must be based on the effective dose (E), meas- not found on MEDLINE. ured in Sieverts (Sv). This description is recommended by the International Commission on Radiological Protection 2.2. Inclusion Criteria for Articles. Initially, articles in English (ICRP) [7] because it considers not only the dose, but also were selected according to their title and abstract, followed the type, quantity, sensitivity, and carcinogenic potential of by a complete reading of the text. The studies included in the the irradiated tissue [8]. Current estimates of per capita analysis fulfilled the following criteria: annual U.S. dose are 6200 µSv with almost 3000 µSv coming from diagnostic procedures. Ubiquitous background sources (1) evaluation of radiation dose in radiographs and/or account for 3100 µSv annual dose or 8.5 µSv per day [9]. CBCT and/or CTs used in dentistry; The effective dose in a given tissue (ET ) is calculated by (2) the use of phantom or thermoluminescent dosime- the following equation [10]: ET = wT · HT ,wherewT is the ters; tissue weighting factor, which represents the radiosensitivity (3) results that showed effective dose and ICRP used; of the tissue/organ and thereby the contribution of this tissue to the total risk, and HT is the equivalent dose for each (4) tomography of the maxilla and/or mandible and/or tissue/organ. The sum ( )oftheET for each tissue/organ the entire head with the assessments of smaller areas provides the total effective dose (E). discarded; The equivalent dose (HT ) for a tissue/organ, in Sv, is re- (5) radiographs included, including a complete peri- presented by the following formula: HT = wR ·DT · fT ,where apical examination, and/or a complete interproxi- wR is the radiation weighting factor (for X-rays, this value is mal examination, and/or a panoramic and/or lat- 1), DT is the mean dose absorbed in the dosimeters in gray eral cephalometric/PA and/or maxillary/mandibular (Gy), and fT is the irradiated fraction of tissue in relation to occlusal examination. its total volume in the body (normal values described in the literature) [11]. The CBCT studies were divided according to their FOV The tissue/organ weighting factors, wT are provided and [11]: small FOV (spherical diameter or cylinder height , ≤ updated by the ICRP (Table 1). The most widely used version 10 cm; captures most of one or both arches, but not all is from 1990 [7] and is based on mortality rates used to esti- of the anatomy of the maxilla); medium FOV (spherical mate the risk of cancers in various tissues. Updates in 2005 diameter or cylinder height between 10 and 15 cm; captures [12] and 2007 [10] included the salivary glands and changes the entire dentition and temporomandibular joints, but in some tissue-weighting factors according to recent rates generally does not include the complete soft profile of the of cancer incidence, which are better descriptors of cancer chin and nose, which is necessary for orthodontic care); burden, especially for those cancer types with high survival large or extended FOV (spherical diameter or cylinder height > rates [13]. The recommendations from 2005 were the draft 15 cm; captures the maxillofacial complex, chin and nose). for the ICRP 2007 recommendations, and the two are, there- fore, relatively comparable. Thus, depending on the version 3. Results of the ICRP recommendations, different effective doses are found for the same level of irradiation. Some articles use the There were 94.742 articles identified with the keyword absorbed dose (Gy), which is less relevant because it does radiation dose, which were reduced to 27 after application not consider the relative contribution of different organs/tis- of the criteria. Table 2 lists these data. It is important to sues to the total risk [14]. know that some of the devices presented in Table 2 are not When using ionizing radiation, the ALARA [15](as the most current versions available. For example, the CBCT low as reasonably achievable) principle must be respected. devices such as Classic i-CAT, NewTom 9000, NewTom 3G, Nevertheless, discussions about radiation doses and their and Iluma already have new versions (Next Generation i- contributing factors do exist, and this requires vigilance in CAT, NewYom 5G and Iluma Elite). The CB MercuRay is not obtaining the best possible cost-benefit relationship between currently available for purchase. They were all kept in Table 2 dosage and information. Consequently, the sources of radia- because they can still be used in some centers. tion used in dentistry (radiography, CBCT, and CT) and the influence of the image acquisition protocol on these doses is 4. Discussion discussed, especially in orthodontics. Methodological variations explain the different doses for the same exam, where these include phantoms made by different 2. Materials and Methods companies or positioned asymmetrically, as well as variations in dosimeters, their sensors [16], their locations on the 2.1. Literature Search Strategy. The literature on radiation phantoms, and their number [17]. Many researchers do not doses used in dentistry was systematically reviewed. The include the calvaria [6, 8, 15, 18–24] and cervical vertebrae articles were located by an online search using MEDLINE [18, 21, 23, 24] when counting the red bone marrow, from 1997 to March 2011. The keyword used in this search esophagus [8, 18–21, 23–26], skin [25], and remaining International Journal of Dentistry 3

Pumped search December 1997 to March 2011 keyword “radiation dose” “Facial” “Buccal” “Face” “Jaw” “Dental” “Mouth” “Dentofacial” “Dentistry” “Tooth” “Cone-beam” 94742 articles “Teeth” “Conebeam” “Maxillofacial” “Cone beam” “Maxilla” “CBCT” “Maxillary” “CB-CT” “Mandible” “Volumetric computed tomography” “Mandibular” “Volumetric CT” “Craniofacial” “CT” Keyword “radiation dose” “Skull” “CT computed tomography” combined with 31 descriptors “Cranial” “Multidetector CT” “Oral” “MDCT” “Multiple row detector CT”

94693 studies excluded by 22 studies excluded by 27 studies included combination with descriptors, inclusion criteria in revision by title or abstract

Figure 1:Flowchartofthesearchprocess.

Table 1: Tissue-weighting factors for calculation of effective radiation dose.

Tissue ICRP 1990 ICRP 2005 ICRP 2007 Bone Marrow 0.12 0.12 0.12 Breast 0.05 0.12 0.12 Colon 0.12 0.12 0.12 Lung 0.12 0.12 0.12 Stomach 0.12 0.12 0.12 Gonads 0.20 0.05 0.08 Esophagus 0.05 0.05 0.04 Bladder 0.05 0.05 0.04 Liver 0.05 0.05 0.04 Thyroid 0.05 0.05 0.04 Bone surface 0.01 0.01 0.01 Brain RT 0.01 0.01 Skin 0.01 0.01 0.01 Salivary glands Not included 0.01 0.01 Kidney RT 0.01 RT Remainder Tissues 0.05a 0.10b 0.12c RT: Remainder tissues; aadrenals/brain /upper large intestine/small intestine/kidney/muscle/pancreas/spleen/thymus/uterus. bAdipose tissue/adrenals/connective tissue/extrathoracic airways/gallbladder/heart wall/lymphatic nodes/muscle/pancreas/prostate/spleen/thymus/uterus/cer- vix. cAdrenals/extrathoracic region/gallbladder/heart/prostate/kidneys/small intestine/lymphatic nodes//muscle/pancreas/spleen/thymus/uterus/cervix (text in boldface represents tissues used for calculation of maxillofacial dose). tissues in the calculation of the effective dose [6, 18, 19, This tissue was incorporated in the ICRP from 2005 [12]and 21, 23, 24]. The ICRP version used is important due to 2007 [10], and this explains the larger doses measured. the inherent variations in the different weighting factors. The 1990 ICRP [7] did not include the salivary glands, which are highly irradiated in dentistry, and some authors 4.1. Image Acquisition Protocol. Increases in kV, mA, and included them among the remainder tissues of the ICRP, exposure time result in higher effective doses for any exam which considerably increased the effective dose (Table 2). [6, 11, 12, 16, 27–29]. The adjustments in CBCT images vary; 4 International Journal of Dentistry

Table 2: Effective doses. (ExcGland or IncGland: salivary glands excluded or included; Mx: Maxilla; Md: Mandible).

Effective Dose (µSv) Exams/equipment/adjustment provided ICRP 60-1990 ICRP 2005 ICRP 103-2007 ExcGland IncGland PANORAMIC RADIOGRAPHS PM2002CCProlinePlanmeca/70 kVp/7 mA/18 s [25]3.8 VeraviewepocsMorita77kV/5mA/8.1s[8]5.2 OrthophosSiemens/62 kV/16 mA/14.1 s [38] 9 16.4 PM2002CCProLinePlanmeca/64 kV/6 mA/15 s [39]49 PromaxPlanmeca/66 kV/6 mA/16 s [16]1726 PM2002CCProlinePlanmeca/73 kV/5 mA/15 s [18]10 Digital/PM2002CCProline2000Planmeca/66 kV/4 mA/18 s [16]812 Digital/PM2002CCProline2000Planmeca/66 kV/8 mA/18 s [16]2338 Digital/CranexExcelSoredex/65 kV/6 mA/19 s [40] 4.5 12.3 Digital/Verawiewepocs5DMorita/70 kV/4 mA/8.2 s [40]2.55.5 Digital/ECProlinePlanmeca/64 kV/7 mA/18.3 s [40] 5.7 14.9 Digital/Orthoralix9200DDEGendex/74 kV/4 mA/12 s [40]2.44.7 Digital/ProMaxPlanmeca/Adult [6]2023 Digital/ProMaxPlanmeca/68 kV/13 mA/16 s [13]7.124.3 Digital/OrthophosXGSirona/64 kV/8 mA/14.1 s [13]4.3 14.2 Digital/OrthophosPlusDSSirona/66 kVp/16 mA/14.1 s [30]6.222 Digital/VeraviewepocsMorita/67 kV/5 mA/8.1 s [8]2.7 Digital/Veraviewepocs3DMorita/70 kV/5 mA/7.4 s [8]2.9 Digital/CranexTomeSoredex/70 kV/4 mA/15 s [40]3.38.1 LATERAL CEPHALOMETRIC RADIOGRAPHS OrthophosCSiemens/77 kV/14 mA/0.5 s [19]2.3 PM2002CCProLinePlanmeca/70 kV/12 mA/0.9 s [39]23 CranexTomeSoredex/70 kVp/10 mA/0.4 s [20]33.7 CranexTomeSoredex/Collimation/70 kVp/10 mA/0.4 s [20]1.62.2 PM2002CCProlinePlanmeca/80 kV/12 mA/0.5 s [18]5 Digital/OrthophosDSCephSiemens/73 kV/15 mA/15.8 s [19]1.1 Digital/ProLineCephCMPlanmeca/Collimation/70 kVp/10 mA/23 s [21]1.73.4 Digital/CranexTomeSoredex/Collimation/70 kVp/4 mAs [21]1.62.2 Digital/InterayVarian/77 kVp/6.5 mAs [13]3.75.6 PA CEPHALOMETRIC RADIOGRAPHS Digital/InterayVarian/75 kVp/11 mAs [13]3.95.1 INTRAORAL RADIOGRAPHS IntraPlanmeca/FullMouthRadiographs/70 kV/8 mA/Digital or F-speed 12.2 34.9 film/RectangularCollimation [13] IntraPlanmeca/FullMouthRadiographs/70 kV/8 mA/Digital or F-speed 58.4 170.7 film/RoundCollimation [13] IntraPlanmeca/FullMouthRadiographs/RoundCollimation/Adult [6] 115 129 IntraPlanmeca/Bitewing(04)/70 kV/8 mA/Digital or F-speed 1 5 film/RectangularCollimation [6] SiemensHeliodent70Dentotime/OcclusalMx [18]7 LARGE FOV CONE BEAM CT Classic i-CAT/FOV22 cm/120 kV/3–8 mA [27] 92.8 182.1 Classic i-CAT/FOV22 cm/120 kV/5.7 mA [12] 134.8 193.4 Classic i-CAT/FOV22 cm/120 kV/3–8 mA/2 × 20 s [28] 82 Next Generation i-CAT/FOV23 cm/120 kV/5 mA/19 mAs/8.9 s [11]37 74 NewTom3G/FOV19 cm/110 kV/1.5 mA/8.09 mAs/36 s [11, 12] 44.7 58.9 68 International Journal of Dentistry 5

Table 2: Continued. Effective Dose (µSv) Exams/equipment/adjustment provided ICRP 60-1990 ICRP 2005 ICRP 103-2007 ExcGland IncGland NewTom3G/FOV19 cm/110 kV/<15 mA [28] 30 NewTom9000/FOV23 cm/110 kV/5.4 mA [15] 56.2 CBMercuRay/FOV19 cm/100 kV/10 mA/100 mAs/10 s [11, 12] 476.6 557.6 569 CBMercuRay/FOV19 cm/120 kV/15 mA/150 mAs/10 s [11, 12] 846.9 1025.4 1073 CBMercuRay/FOV19 cm/100 kV/15 mA [6] 415 479 CBMercuRay/FOV19 cm/120 kV/15 mA [6] 656 761 CBMercuRay/FOV19 cm/100 kV/10 mA [6] 264 306 CBMercuRay/FOV19 cm/100 kV/5 mA [6] 153 177 CBMercuRay/FOV19 cm/100 kV/2 mA [6]7586 Iluma/FOV19 cm/120 kV/1 mA/20 mAs/20 s [11]5098 Iluma/FOV19 cm/120 kV/3.8 mA/152 mAs/40 s [11] 252 498 Kodak9500/FOV18 cm/80 kV/86.4 mAs [29]5293 Kodak9500/FOV18 cm/85 kV/108 mAs [29] 92 163 Kodak9500/FOV18 cm/90 kV/108 mAs [29] 148 260 Kodak9500/FOV18 cm/90 kV/108 mAs [17] 136 SkyView/FOV17 cm/90 kV/51 mAs [17] 87 MEDIUM FOV CONE BEAM CT Classic i-CAT/FOV13 cm/120 kV/3–8 mA [27] 39.5 110.5 Classic i-CAT/FOV13 cm/120 kV/5.7 mA [12] 68.7 104.5 Classic i-CAT/FOV13 cm/120 kV/23.87 mA [15] 61.1 Classic i-CAT/FOV13 cm/120 kV/3–8 mA/10 s [28]48 Classic i-CAT/FOV13 cm/120 kV/3–8 mA/40 s [28]77 Classic i-CAT/FOV13 cm/120 kV/5 mA/19 mAs/20 s [11]2969 Next Generation i-CAT/FOV13 cm/120 kV/5 mA/19 mAs/8.9 s [11]3687 Next Generation i-CAT/FOV13 cm/120 kV/18.5 mAs [17]83 NewTom9000/FOV13 cm/110 kV/3.2 mA [30] 36.9 77.9 NewTom9000/FOV13 cm/110 kV/3.5 mA/18 s [26] 50.3 NewTom9000/FOV13 cm/110 kV/3.4 mA/17 s [22]3564 NewTom9000/FOV13 cm/110 kV/3.4 mA/17 s/Thyroid Protector [22]2352 NewTom3G/FOV15 cm/110 kV/<15 mA [28] 57 NewTom5Gi/FOV15 cm/110 kV/8.8 mAs [17] 194 CBMercuRay/FOV15 cm/120 kV/15 mA/120/mAs/10 s [11] 288.9 435.5 560 CBMercuRay/FOV15 cm/100 kV/15 mA [6] 354 402 CBMercuRay/FOV15 cm/120 kV/15 mA [6] 601 680 Galileos/FOV15 cm/85 kV/5 mA/21 mAs/14 s [11]2870 Galileos/FOV15 cm/85 kV/7 mA/42 mAs/14 s [11] 52 128 GalileosComfort/FOV15 cm/85 kV/28 mAs [17] 84 Kodak9500/FOV15 cm/80 kV/86.4 mAs [29]3976 Kodak9500/FOV15 cm/85 kV/108 mAs [29]4998 Kodak9500/FOV15 cm/90 kv/108 mAs [29] 76 166 IlumaElite/FOV14 cm/120 kV/76 mAs [17] 368 Scanora3D/FOV13.5 cm/85 kV/48 mAs [17] 68 SMALL FOV CONE BEAM CT Classic i-CAT/FOV6 cmMx/120 kV/3–8 mA [27] 9.7 36.5 Classic i-CAT/FOV6 cmMx/120 kV/3–8 mA/HighResolution [27] 18.5 68.3 Classic i-CAT/FOV6 cmMx/120 kV/3–8 mA/20 s [28]45 Classic i-CAT/FOV6 cmMx/120 kV/3–8 mA/40 s [28]77 6 International Journal of Dentistry

Table 2: Continued. Effective Dose (µSv) Exams/equipment/adjustment provided ICRP 60-1990 ICRP 2005 ICRP 103-2007 ExcGland IncGland Classic i-CAT/FOV6 cmMd/120 kV/3–8 mA [27] 23.9 75.3 Classic i-CAT/FOV6 cmMd/120 kV/3–8 mA/HighResolution [27] 47.2 148.5 Classic i-CAT/FOV6 cmMd/120 kV/3–8 mA/20 s [28] 34 Classic i-CAT/FOV6 cmMd/120 kV/3–8 mA/40 s [28] 64 Classic i-CAT/FOV8 cm/120 kV/3–8 mA/40 s [28] 37 Next Generation i-CAT/FOV6 cmMd/120 kV/18.5 mAs [17] 45 NewTom9000/FOVMx [30] 19.9 41.5 NewTom9000/FOVMd [30] 34.7 74.7 NewTom5G/FOV10 cm/110 kV/10.4 mAs [17] 83 NewTom5Gi/FOV8 cm/110 kV/43 mAs [17] 265 CBMercuRay/FOV10 cmMx/120 kV/15 mA/150 mAs/10 s [11, 12] 168.4 283.3 407 CBMercuRay/FOV10 cm/100 kV/15 mA [6] 328 369 CBMercuRay/FOV10 cm/120 kV/15 mA [6] 535 603 CBMercuRay/FOV10 cm/120 kV/15 mA [23] 451.8 510.5 Promax3D/FOV8 cm/84 kVp/12 mA/6 s [41] 269 674 Promax3D/FOV8 cm/84 kV/12 mA/72 mAs/18 s [11] 151 488 Promax3D/FOV8 cm/84 kV/16 mA/96 mAs/18 s [11] 203 652 Promax3D/FOV8 cm/84 kV/8 mA/12 s/NormalResolution [42] 102 Promax3D/FOV8 cm/84 kV/10 mA/12 s/NormalResolution [42] 169 Promax3D/FOV8 cm/84 kV/12 mA/12 s/NormalResolution [42] 216 Promax3D/FOV8 cm/84 kV/14 mA/12 s/NormalResolution [42] 272 Promax3D/FOV8 cm/84 kV/16 mA/12 s/NormalResolution [42] 298 Promax3D/FOV8 cm/84 kV/8 mA/2.8 s/LowDose [42] 30 Promax3D/FOV8 cm/84 kV/16 mA/12 s/HighDose [42] 306 Promax3D/FOV8 cm/84 kV/8 mA/8.3 s/LowDose [42] 87 Promax3D/FOV8 cm/84 kV/169 mAs/HighDose [17] 122 Promax3D/FOV8 cm/84 kV/19.9 mAs/LowDose [17] 28 PreXion3D/FOV8.1 cm/90 kV/4 mA/76 mAs/19 s [11]66 189 PreXion3D/FOV8.1 cm/90 kV/4 mA/148 mAs/37 s [11] 154 388 3D Accuitomo 170/FOV5 cmMx/90 kV/87.5 mAs [17] 54 Kodak9500/FOV8 cm/90 kV/108 mAs [17] 92 PicassoTrio HighDose/FOV7 cm/85 kV/127 mAs [17] 123 PicassoTrio LowDose/FOV7 cm/85 kV/91 mAs [17] 81 Scanora 3D/FOV7.5 cmMx/85 kV/30 mAs [17] 46 Scanora 3D/FOV7.5 cmMd/85 kV/30 mAs [17] 47 Scanora 3D/FOV7.5 cmMxMd/85 kV/30 mAs [17] 45 Veraviewpocs3D/FOV8 cm/70 kV/51 mAs [17] 73 CONVENTIONAL CT SomatomVolumeZoom4/Scan22.6 cmFullHead/120 kV/ 1110 90 mA/44.12 s/Slice0.75 mm [28] SomatomSensation16/Scan22.5 cmFullHeadl/120 kV/90 mA/ 995 29.48 s/slice0.75 mm [28] Mx8000IDTPhilips/Scan22.5 cmFullHead/120 kV/140 mA/29.6 s/Slice0.75 mm [28] 1160 Somatom64/Scan12 cm/120 kV/90 mA [11] 453 860 Somatom64CareDose4D/Scan12 cm/120 kV/90 mA [11] 285 534 SomatomPlusVolumeZoom4/ScanMx+Md/Slice1.25 mm/21.25 s/120 kVp/ 2110 150 mA [18] International Journal of Dentistry 7

Table 2: Continued. Effective Dose (µSv) Exams/equipment/adjustment provided ICRP 60-1990 ICRP 2005 ICRP 103-2007 ExcGland IncGland SomatomSensation/Scan10 cm/120 kV/90 mA [15] 429.7 ExcelTwin/Scan9.6 cm/120 kV/300 mAs/Slice2 mm/2sporslice [39] 314 924 HiSpeedQX/i/Scan7.7 cmMx+Md/120 kV/100 mA [23] 595.6 768.9 SomatomVolumeZoom4/Scan7.2 cmMd/120 kV/90 mA/15.16 s/ Slice0.75 mm [28] 494 SomatomSensation16/Scan6.3 cmMd/120 kV/90 mA/7.87 s/Slice0.75 mm [28] 474 Mx8000IDTPhilips/Scan6 cmMd/120 kV/140 mA/7.89 s/ Slice0.75 mm [28] 541 SomatomPlus4VolumeZoom Scan5.2 cmMd/120 kV/100 mAs [24] 250 ElscintExcel2400/ScanMd/120 kVp/315 mAs [43] 2426 3324 SomatomPlus4VolumeZoom/ScanMd/Slice1.25 mm/12.64 s/ 120 kVp/150 mA [18] 1320 SomatomPlusVolumeZoom4/ScanMx/Slice1.25 mm/9.47 s/ 120 kVp/150 mA [18] 1400 ElscintExcel2400/ScanMx/120 kVp/315 mAs [43] 1031 1202

for the i-CAT, the kV, mA, and exposure time are established especially in relation to the NewTom 3G and i-CAT CBCT by the manufacturer and do not vary from patient to patient. devices. The CT dose is also high in relation to radiographs, That is, the same dose is used for patients of different sizes which emit doses of 14.2 to 24.3 µSv for the panoramic and different ages. In children, this may be higher than radiograph, 5.4 µSv for the lateral cephalometric radiograph needed for a diagnosis. For the NewTom 3G, exposure is also and 34.9 to 170.7 µSv for a complete intraoral examination. set by the manufacturer, but a dynamic process identifies the radiation needed, and the mA is adjusted during the 4.3. CBCT versus Conventional Radiographs. In this tran- exposure. For the CB MercuRay, the operator defines kV and sition phase of image diagnosis, a question frequently mA. Inexperienced operators tend to increase kV and mA arises: “to how many radiographs is the radiation dose of because the overexposed images appear to be adequate with CBCT equivalent?” Despite the straightforward nature of the reduced noise, which increases the risk of overexposure [12]. question, the answer involves many nuances. For CBCT, smaller FOV normally generates lower radia- The characteristics of an intraoral radiograph influence tion doses, similar to the action of collimators [6, 12, 17, 27– its effective dose, such as film sensitivity (when not digital) 29]. In general, the mandibular FOV has a larger dose than and, especially, the type of collimation (rectangular or the maxillary [27, 30], because the salivary glands, thyroid, circular). Intraoral radiographs with circular collimation and and esophagus are more irradiated in this exam. The chosen films that are not sensitive (D-speed) yielding doses that are FOV must be the smallest that will encompass the region of much greater than sensitive (E/F-speed) and digital films interest [6]. For example, the medium FOV (13 cm) from with rectangular collimation. The dose for the digital/F- the NewTom/i-CAT is often enough to reach the regions speed complete intraoral exam with rectangular collimation required in many children for orthodontics. With the large (34.9 µSv) is close to 4.9 times lower than one with circular FOV, unnecessary areas are irradiated in these “minor” collimation (170.7 µSv) [13]. The NCRP [31] and the children, increasing the effective dose. On the other hand, American Dental Association [32] recommend rectangular the large FOV is always necessary in adults. The operator collimation for periapical and bitewing radiographs, the use is responsible for choosing the appropriate FOV, large or of a thyroid protector and the avoidance of using films medium, according to the size of the child. lower than E-speed (preferably F-speed/digital). In terms of extraoral radiographs, according to ICRP 2005/2007, the 4.2. CBCT versus CT. The effectivedosegeneratedbyCTis doses are between 2.7 and 24.3 µSv for the panoramic and generally higher than that of CBCT. When analyzing the dose 5.6 µSv for the lateral cephalometric. according the 2007 ICRP,the head CT requires doses between Many orthodontists do not request a full-mouth series 995 and 1160 µSv, whereas the large FOV CBCT requires 30 of intraoral radiographs for orthodontic planning and this to 68 µSv for the NewTom 3G, 74 µSv for the Next Generation practice greatly reduces the dose of radiation imparted to i-CAT, 82 to 182.1 µSv for the Classic i-CAT, 87 µSv for the patient when compared to CBCT exposure. This is the SkyView, 93 to 260 µSv for the Kodak 9500, and 98 to particularly important when dealing with young children 498 µSv for the Iluma. The CB MercuRay approaches the that are more susceptible to radiation [4]. However, in some radiation levels of standard CT, with doses between 569 and instances, it hampers the diagnosis since the panoramic 1073 µSv. High doses are observed for CT even when areas radiograph shows large distortions that prevent the diagnosis are reduced, ranging between 534 and 860 µSv for the maxilla of more subtle changes, such as caries and root resorption and mandible. This represents a higher dose emitted by CT, in early stages. Thus, these radiographs should be taken in 8 International Journal of Dentistry patients with permanent dentition that will begin full braces radiographic methods such as panoramic, intraoral radio- orthodontic treatment to search for dental and to graphy, and conventional CT. The range of doses among serve as a precise record of each teeth and adjacent bone devices is too large to consider them as a single modality during and posttreatment. Panoramics should also be taken [17]. during comprehensive orthodontic treatment to visualize the In addition to controlling the settings of tomographs, entire maxilla and mandible including the teeth, maxillary radiation levels can vary due to exposure times and radiation sinuses, nasal cavity, and condyles. beams. The NewTom 3G scans in 36 s but emits X-ray for Therefore, in the initial orthodontic radiographic doc- only 5.4 s. Similarly, the Classic i-CAT (FOV 13 cm) scans in umentation (ORD), which often includes full mouth series 20 s, but the X-ray tube is only activated for 3.3 s. The large of intraoral radiographs (FMX), panoramic, and lateral FOV in the i-CAT involves two FOV 13 cm scans, performed cephalometric radiographs, the total dose varies between sequentially and interlaced to create a greater volume. Dou- 43.2 and 200.6 µSv, depending on the collimation of intraoral ble scanning preserves the quality of FOV 13 cm but requires radiographs. The large FOV of most CBCT scanners provides almost double the exposure time. The CB MercuRay scans in lower doses than the ORD with FMX using circular colli- 11 s and emits for 10 s. Thus, the exposure for the CB Mer- mation. If rectangular collimation is used, the ORD presents cuRay is continuous, whereas for the NewTom 3G and the lower effective dose. i-CAT it is pulsed; consequently, the latter two use radiation It is not enough to compare doses between diagnostic more efficiently because the detector is only exposed while procedures, because diagnostic quality cannot be separated it registers photons and because radiation is not emitted from the dose used. Objective studies of the impact of CBCT while the detector transfers the image signal to the computer image quality on diagnostic performance must be conducted [12]. before any definitive conclusions are drawn about the differ- The results of the CBCT devices expressed in Table 2 ences generated by reduced doses [12]. Current data describe should be interpreted carefully due to the interplay among the reconstructions of lateral teleradiography of CBCT as image quality, the size of the scanned volume, and the having similar precision to conventional radiographs [33] absorbed radiation dose in different tissues. Comparisons in addition to high intra- and interexaminer reproducibil- of the performances of CBCT devices cannot be done ity [34]. Comparisons between CBCT images, periapical based on dosimetric results alone. The radiation dose from radiography, and clinical evaluations have not demonstrated these devices can be seen as a function of the diagnostic significant differences in the extent of periodontal defects, application. The two key factors for an acceptable image but CBCT allows for the observation of all bone defects are an appropriate size and positioning of the FOV and an and better inspection of craters and furcation defects [35]. acceptable quality of the reconstructed image [17],apoint However, delicate structures such as the trabecular bone and that was not evaluated in this revision. Further study is the periodontal ligament display lower visibility and higher required to bring the image quality into play, on a technical variability between CBCT and CT than do other structures and diagnostic level. By investigating technical image quality, [36]. Conventional radiography has advantages in terms of the relation between the exposure from CBCT devices and contrast, the quality of the bone image and delineation of the the image quality performance can be quantified [17]. lamina dura, in addition to superior performance in the eval- uation of the periodontal space compared to CBCT [37]and 5. Conclusions is, therefore, indispensable for accurate periapical diagnosis. (1) Increases in kV, mA, exposure time, and FOV in- ff 4.4. Di erences between CBCT Devices. TheCBCTdosevar- crease the dose of radiation, regardless of the type of ies according to the CBCT device. Among the better known exam. large FOV CBCT, the CB MercuRay provides the greatest ff radiation, followed by the Classic i-CAT, the Kodak 9500, (2) The e ective dose for CT is greater than for CBCT or the Iluma, the Next Generation i-CAT, and the NewTom 3G. conventional radiographs. Considering the large FOV (ICRP2005) [12], the radiation (3) When the FMX is performed with round collimation, doses of the Classic i-CAT and the CB MercuRay are 3.3 and the ORD issues higher doses than most of the large 9.5 to 17 times greater, respectively, than that of the NewTom FOV CBCT. Radiation dose for ORD can be lower 3G. The Next Generation i-CAT comes close to the NewTom than large FOV CBCT if rectangular collimation is 3G (ICRP 2007) in terms of radiation level because it scans used in FMX. Despite the image quality, CBCT does more quickly than the Classic i-CAT. not replace the FMX and most orthodontic cases Considering the large FOV CBCT, a general conclusion, will be properly handled with conventional 2D radio- ff based on values described in Table 2, is that the e ective graphs. CBCT should be required for more complex µ doses from most devices are found in the 30–200 Sv range. cases. Although the geometry of image acquisition is basically the same, the differences in collimation of the cone beam, (4) The orthodontists have the duty to preserve the as well as the X-ray exposure factors, lead to considerable health of the patient and always seek the best treat- differences in absorbed dose for all organs in the head and ment. This quest begins with exams that require the the neck regions. A single effective dose is not a concept least amount of radiation dose to treat the patient that should be used for CBCT when compared to alternative appropriately. International Journal of Dentistry 9

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[30] J. B. Ludlow, L. E. Davies-Ludlow, and S. L. Brooks, “Dosime- try of two extraoral direct digital imaging devices: newTom cone beam CT and Orthophos Plus DS panoramic unit,” Dentomaxillofacial Radiology, vol. 32, no. 4, pp. 229–234, 2003. [31] D. A. Miles and R. P. Langlais, “NCRP Report No. 145: new dental x-ray guidelines: their potential impact on your dental practice,” Dentistry Today, vol. 23, no. 9, pp. 128–134, 2004. [32] American Dental Association Council on Scientific Affairs, “The use of dental radiographs: update and recommenda- tions,” TheJournaloftheAmericanDentalAssociation, vol. 137, no. 9, pp. 1304–1312, 2006. [33] V. Kumar, J. B. Ludlow, A. Mol, and L. Cevidanes, “Compari- son of conventional and cone beam CT synthesized cephalo- grams,” Dentomaxillofacial Radiology, vol. 36, no. 5, pp. 263– 269, 2007. [34] A. E. F. de Oliveira, L. H. S. Cevidanes, C. Phillips, A. Motta, B. Burke, and D. Tyndall, “Observer reliability of three-dimensional cephalometric landmark identification on cone-beam computerized tomography,” Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology and Endodontology, vol. 107, no. 2, pp. 256–265, 2009. [35] K. A. Misch, E. S. Yi, and D. P. Sarment, “Accuracy of cone beam computed tomography for periodontal defect measure- ments,” Journal of Periodontology, vol. 77, no. 7, pp. 1261– 1266, 2006. [36] X. Liang, R. Jacobs, B. Hassan et al., “A comparative evaluation of cone beam computed tomography (CBCT) and multi-slice CT (MSCT) Part I. On subjective image quality,” European Journal of Radiology, vol. 75, no. 2, pp. 265–269, 2010. [37] N. Ozmeric,I.Kostioutchenko,G.H¨ agler,¨ M. Frentzen, and P. -M. Jervøe-Storm, “Cone-beam computed tomography in assessment of periodontal ligament space: in vitro study on artificial tooth model,” Clinical Oral Investigations, vol. 12, no. 3, pp. 233–239, 2008. [38] A. R. Lecomber, S. L. Downes, M. Mokhtari, and K. Faulkner, “Optimisation of patient doses in programmable dental pano- ramic radiography,” Dentomaxillofacial Radiology, vol. 29, no. 2, pp. 107–112, 2000. [39] A. R. Lecomber, Y. Yoneyama, D. J. Lovelock, T. Hosoi, and A. M. Adams, “Comparison of patient dose from imaging pro- tocols for dental implant planning using conventional radiog- raphy and computed tomography,” Dentomaxillofacial Radiol- ogy, vol. 30, no. 5, pp. 255–259, 2001. [40] F. Gijbels, R. Jacobs, R. Bogaerts, D. Debaveye, S. Verlinden, and G. Sanderink, “Dosimetry of digital panoramic imaging. Part I: patient exposure,” Dentomaxillofacial Radiology, vol. 34, no. 3, pp. 145–149, 2005. [41] A. Suomalainen, T. Kiljunen, Y. Kaser,J.Peltola,andM.¨ Kortesniemi, “Dosimetry and image quality of four dental cone beam computed tomography scanners compared with multislice computed tomography scanners,” Dentomaxillofa- cial Radiology, vol. 38, no. 6, pp. 367–378, 2009. [42] X. M. Qu, G. Li, J. B. Ludlow, Z. Y. Zhang, and X. C. Ma, “Effective radiation dose of ProMax 3D cone-beam comput- erized tomography scanner with different dental protocols,” Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology and Endodontology, vol. 110, no. 6, pp. 770–776, 2010. [43] G. Scaf, A. G. Lurie, K. M. Mosier, M. L. Kantor, G. R. Ramsby, and M. L. Freedman, “Dosimetry and cost of imaging osseointegrated implants with film-based and computed to- mography,” Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics, vol. 83, no. 1, pp. 41–48, 1997. Hindawi Publishing Corporation International Journal of Dentistry Volume 2012, Article ID 745265, 5 pages doi:10.1155/2012/745265

Research Article Supernumerary Teeth in Indian Children: A Survey of 300 Cases

Amita Sharma1 and Varun Pratap Singh2

1 Department of Pediatric Dentistry, College of Dental Sciences, BPKIHS, Dharan, Nepal 2 Department of Orthodontics, College of Dental Sciences, BPKIHS, Dharan, Nepal

Correspondence should be addressed to Varun Pratap Singh, [email protected]

Received 11 July 2011; Revised 19 December 2011; Accepted 10 January 2012

Academic Editor: Preetha Kanjirath

Copyright © 2012 A. Sharma and V. P. Singh. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

The aim of this investigation was to study children with supernumerary teeth who visited the Department of Pedodontics and Preventive Dentistry, Government Dental College and Hospital, Rohtak, Haryana, India. Only children with supernumerary teeth were included in the study while patients having supernumerary teeth with associated syndromes were excluded. Supernumeraries were detected by clinical and radiographic examination. The results indicated that males were affected more than females with a sex ratio of 2.9 : 1. Single supernumerary tooth was seen in 79% of the patients, 20% had double, and 1% had three or more supernumeraries. Premaxillary supernumeraries accounted for 93.8% of the cases. Conical shaped supernumerary teeth were the most common type (59.7%). Majority of supernumeraries remained unerupted (65%). Fusion of supernumerary tooth with a regular tooth was observed in 4% of the patients. Talon , an associated dental anomaly, was seen in 5% of the cases. Simultaneous occurred in 2.3% of patients with supernumeraries.

1. Introduction Cleidocranial dysplasia, Gardner’s syndrome, and so forth [5, 6]. Supernumerary teeth () may be defined as extra Supernumerary teeth may be classified according to their teeth—more than twenty in the deciduous dentition or more form/morphology (supplemental or rudimentary including than thirty-two in the permanent dentition [1]. The etiology conical, tuberculate, and molariform types) and location of supernumerary teeth is not well understood. Several the- (mesiodens, paramolar, and distomolar). Detection of super- ories have been put forward to explain the anomaly. One numerary teeth is best achieved with a thorough clinical theory suggests that supernumeraries are formed as a result and radiographic examination. Many complications can of local, conditioned hyperactivity of dental lamina while be associated with supernumeraries like crowding, delayed another theory proposes dichotomy of tooth bud. Heredity eruption, impaction, abnormal diastema, cystic lesions, ec- plays an important role in the occurrence of supernumerary topic eruption, root resorption of adjacent teeth, and so teeth but does not follow a simple Mendelian pattern. A forth. An early diagnosis allows an early intervention, a more familial tendency and sex-linked inheritance (males being favourable prognosis, and minimal complications [7]. affected twice as frequently as females) has been demon- The purpose of this study was to investigate the charac- strated [2–4]. teristics of supernumerary teeth among children who report- Supernumerary teeth occur in 0.3 to 3.8 percent of dif- ed to our specialty clinic and compare the data with other ferent populations and appear to be on the rise. Out of similar studies. these 90 to 98 percent occur in the maxilla with a particular predilection for the premaxilla. Supernumerary teeth may be 2. Material and Method single or multiple, unilateral or bilateral, erupted or impact- ed and in one or both jaws. Multiple supernumerary teeth A survey was performed on 21,824 patients (11,218 females are rare and usually seen in association with cleft lip/palate, and 10,606 males) attending the Department of Pedodontics 2 International Journal of Dentistry

Table 1: Distribution of supernumerary teeth by dentition and sex. ∗Denotes statistically significant values (P<0.01).

Type of dentition Male Female Total P Value Deciduous 15 5 20 0.002∗ Mixed 142 39 181 0.001∗ Permanent 67 32 99 0.017 Total 224 76 300 0.002∗

Table 2: Distribution of supernumerary teeth by number per patient.

Number of teeth Percentage of Number of patients per patient supernumerary teeth Figure 1: Radiographic appearance of an erupted supplemental One 237 79.0 21 along with an unerupted tuberculate supernumerary tooth in Two 60 20.0 maxillary central region. Three or more 03 01.0 Total 300 100.0

Table 3: Type of supernumerary tooth.

Type Number Percentage Supplemental (Eumorphic) 70 18.2 Rudimentary (Dysmorphic): Conical 230 59.7 Tuberculate 55 14.3 Molariform 30 07.8 Total 385 100.0 and Preventive Dentistry, Government Dental College and Figure 2: Two unerupted normally oriented conical supernumer- Hospital, Rohtak, Haryana, India over a period of six years. ary teeth causing failure of eruption of 11 and 21. Out of the total population, 300 children with ages ranging from4to14yearswerediagnosedwithsupernumeraryteeth in different regions of the dental arches. Reasons for visiting supernumerary tooth (Table 2) which was conical in form included caries, , lack of eruption of permanent (Table 3). teeth, and routine dental check up. The characteristics of Supernumerary teeth located in the premaxilla were 361 supernumerary teeth were noted and diagnosis made during (93.8%), and out of these, 293 (81.2%) supernumeraries clinical and radiographic examination with help of occlusal, were located in the central incisor region (Figure 1), of which periapical, and panoramic radiographs. The horizontal shift 88 (30.0%) were in midline (mesiodens). Sixty-eight super- technique was used to determine the sagittal position of the numerary teeth were seen in maxillary lateral incisor region impacted supernumerary teeth. Surgical removal of teeth (18.8%). The remaining teeth were located in premolar when and where indicated further confirmed the character- (3.6%), canine (1.0%), and mandibular incisor (1.5%) istics of supernumeraries. Patients with syndromes known to regions. A large percentage of supernumerary teeth remained be predisposed to supernumerary teeth such as Cleidocranial unerupted (65%), while 35% were partially or fully erupted dysplasia, Gardner’s syndrome, clefts of lip, and palate were (Figures 2 and 3). not included in the study. All the radiographs were reviewed Rotation/displacement of adjacent was in a negatoscope and interexaminer discrepancies were the most frequently found complication. Three cases of solved by mutual consensus. The Pearson chi-square test was dentigerous cyst associated with supernumerary teeth were used to determine potential differences in the distribution of detected (Figure 4). supernumerary teeth when stratified by gender. P value of In 4% of the patients fusion of supernumerary tooth with less than 0.01 was considered statistically significant. the adjacent normal tooth occurred. , an associ- ated dental anomaly was seen in 5% of the cases (Figure 5). 3. Results Taloncusponsupernumeraryteethwasobservedin2% of the patients (Figure 6). Out of 300 patients, 224 were male, and 76 were female, the Seven patients with supernumerary teeth were found sex ratio was 2.9 : 1 (Table 1). having simultaneously congenitally absent teeth (excluding The total number of supernumerary teeth was 385 third molars), that is, concomitant hypohyperdontia was among the 300 patients. Majority of the patients had single observed in 2.3% of the cases (Figure 7). International Journal of Dentistry 3

Figure 3: Bilateral unerupted (inverted) conical mesiodentes ob- served during radiographic examination of fractured anterior teeth. Figure 6: A well-developed mesiodens with talon cusp: a typical superimposed inverted V-shaped radiopaque structure.

Figure 7: Panoramic radiograph showing bilaterally erupted sup- plemental mesiodentes; fusion of 61 and 62 and missing 22. Figure 4: Maxillary occlusal radiograph showing two impacted supernumerary teeth. One on the right side is associated with a radiolucency having sclerotic border suggestive of dentigerous cyst. (Table 3). Koch et al. reported 56% conical, 12% tubercular, and 11% supplemental and 12% other configurations among their patients [14]. In this study, 35% of the supernumerary teeth were erupted which is higher than that reported in Mckibben’s study but comparable to Liu’s study [2, 12]. Few authors have reported around 20% of erupted supernumeraries [13, 15]. The association of talon cusp with other odontogenic anomalies reported in the literature includes peg-shaped lat- eral , supernumerary teeth, and , megadont [16, 17]. Very few cases of talon cusp on super- numerary teeth have been reported [18, 19]. Concomitant hypohyperdontia is a rare condition of mixed numeric variation in human dentition. It is usually mentioned as individual case reports in the literature [20]. Its prevalence in orthodontic patients (including third molars) has been Figure 5: Occlusal radiograph showing talon cusp on 12 and 22; reported to be 0.4% [21, 22]. In the present survey on Indian fusion of 22 and supplemental supernumerary 22. children, a high incidence of other dental anomalies like talon cusp and concomitant hypodontia were seen to be asso- ciated with supernumerary teeth while Celikoglu et al. found 4. Discussion no such associated dental anomalies in Turkish population [23]. Dentists should take cognizance of associated dental Table 4 provides an overview of studies done on supernu- anomalies during the examination for supernumerary teeth merary teeth in different populations. Supernumerary teeth so that a comprehensive treatment can be rendered. most commonly involved the premaxilla which has also been Furthermore as supernumerary teeth are often associated established as the predominant location by others [2, 5, with delayed eruption or impaction of permanent teeth, 11–13]. Supernumeraries appeared in a variety of forms early removal is recommended to facilitate the spontaneous (size and shape). Most common was conical, followed by eruption of impacted permanent teeth [24]. In one interest- supplemental, then by tuberculate and molariform type ing study Ashkenazi et al. demonstrated that spontaneous 4 International Journal of Dentistry

Table 4: Summary of various studies carried out on supernumerary teeth in different populations.

Types of Authors Sample size Country Age Method supernumerary Male : Female included 300 children diagnosed with Clinical Present study supernumerary India 4–14 Yeras Examination and All 2.9 : 1 teeth radiographs 97 children with Tyrologou et al. Clinical examination diagnosed Sweden 3–15 years Mesiodens 2 : 1 (2005) [8] mesiodens and radiographs 152 children with Huang et al. diagnosed Clinical examination Jordan 5–15 years All 2.2 : 1 (1992) [9] supernumerary and radiographs teeth 112 children with diagnosed supernumerary Clinical examination In the Premaxillary Liu (1995) [2] Taiwan 4–14 years 2.8 : 1 teeth in the and radiographs region. premaxillary regions 90 patients with von Arx (1992) Clinical examination In the Anterior anterior maxillary Switzerland 6–10 years 2.6 : 1 [10] supernumerary and radiographs Maxillary region

eruption of permanent teeth depends on various variables [8] S. Tyrologou, G. Koch, and J. Kurol, “Location, complications like apex distance of the impacted tooth relative to its fi- and treatment of mesiodentes—a retrospective study in nal position, extent of vertical impaction, morphology of children,” Swedish Dental Journal, vol. 29, no. 1, pp. 1–9, 2005. supernumerary teeth, angle of impaction relative to midline, [9] W. H. Huang, T. P. Tsai, and H. L. Su, “Mesiodens in the and time of surgery. However the authors recommended im- primary dentition stage: a radiographic study,” ASDC Journal mediate orthodontic traction at the time of removal of su- of Dentistry for Children, vol. 59, no. 3, pp. 186–189, 1992. pernumerary teeth [25]. [10] T. von Arx, “Anterior maxillary supernumerary teeth: a clinical and radiographic study,” Australian Dental Journal, vol. 37, no. 3, pp. 189–195, 1992. References [11] J. R. Luten, “The prevalence of supernumerary teeth in pri- mary and mixed dentitions,” Journal of Dentistry for Children, [1] C. Schulze, “Developmental abnormalities of the teeth and vol. 34, no. 5, pp. 346–353, 1967. jaws,” in Thoma’s Oral Pathology, R. J. Gorlin and H. M. Gold- [12] D. R. McKibben and L. J. Brearley, “Radiographic deter- man, Eds., The CV Mosby Co., St Louis, Mo, USA, 6th edition, mination of the prevalence of selected dental anomalies in 1970. children,” ASDC Journal of Dentistry for Children, vol. 28, no. [2] J.F.Liu,“Characteristicsofpremaxillarysupernumeraryteeth: 6, pp. 390–398, 1971. asurveyof112cases,”ASDC Journal of Dentistry for Children, vol. 62, no. 4, pp. 262–265, 1995. [13] L. D. Rajab and M. A. M. Hamdan, “Supernumerary teeth: [3] A. H. Brook, “A unifying aetiological explanation for anoma- review of the literature and a survey of 152 cases,” International lies of number and size,” Archives of Oral Biology, Journal of Paediatric Dentistry, vol. 12, no. 4, pp. 244–254, vol. 29, no. 5, pp. 373–378, 1984. 2002. [4] M. J. Kinirons, “Unerupted premaxillary supernumerary [14] H. Koch, O. Schwartz, and B. Klausen, “Indications for sur- teeth. A study of their occurrence in males and females,” gical removal of supernumerary teeth in the premaxilla,” British Dental Journal, vol. 153, no. 3, p. 110, 1982. International Journal of Oral and Maxillofacial surgery, vol. 15, [5]M.M.Nazif,R.C.Ruffalo, and T. Zullo, “Impacted supernu- no. 3, pp. 273–281, 1986. merary teeth: a survey of 50 cases,” The Journal of the American [15] C. De Oliveira Gomes, S. N. Drummond, B. C. Jham, E. N. Dental Association, vol. 106, no. 2, pp. 201–204, 1983. Abdo, and R. A. Mesquita, “A survey of 460 supernumerary [6] R. E. Primosch, “Anterior supernumerary teeth—assessment teethinBrazilianchildrenandadolescents,”International and surgical intervention in children,” Pediatric Dentistry, vol. Journal of Paediatric Dentistry, vol. 18, no. 2, pp. 98–106, 2008. 3, no. 2, pp. 204–215, 1981. [16] C. L. Mader, “Talon cusp,” The Journal of the American Dental [7] F. N. Hattab, O. M. Yassin, and M. A. Rawashdeh, “Supernu- Association, vol. 103, no. 2, pp. 244–246, 1981. merary teeth: report of three cases and review of the literature,” [17] P. J. Davis and A. H. Brook, “The presentation of talon cusp: ASDC Journal of Dentistry for Children,vol.61,no.5-6,pp. diagnosis, clinical features, associations and possible aetiol- 382–393, 1994. ogy,” British Dental Journal, vol. 160, no. 3, pp. 84–88, 1986. International Journal of Dentistry 5

[18] M. A. O. Al-Omari, F. N. Hattab, A. M. G. Darwazeh, and P. M. H. Dummer, “Clinical problems associated with unusual cases of talon cusp,” International Endodontic Journal, vol. 32, no. 3, pp. 183–190, 1999. [19] F. S. Salama, C. M. Hanes, P. J. Hanes, and M. A. Ready, “Talon cusp: a review and two case reports on supernumerary pri- mary and permanent teeth,” ASDC Journal of Dentistry for Children, vol. 57, no. 2, pp. 147–149, 1990. [20] J. Zhu, M. Marcushamer, D. L. King, and R. J. Henry, “Super- numerary and congenitally absent teeth: a literature review,” Journal of Clinical Pediatric Dentistry, vol. 20, no. 2, pp. 87–95, 1996. [21] A. C. Gibson, “Concomitant hypo-hyperodontia,” British Journal of Orthodontics, vol. 6, no. 2, pp. 101–105, 1979. [22] I. B. O’Dowling, “Hypo-hyperdontia in an Irish population,” Journal of the Irish Dental Association, vol. 35, no. 3, pp. 114– 117, 1989. [23] M. Celikoglu, H. Kamak, and H. Oktay, “Prevalence and characteristics of supernumerary teeth in a non-syndrome Turkish population: associated pathologies and proposed treatment,” Medicina Oral, Patologia Oral y Cirugia Bucal, vol. 15, no. 4, pp. e575–e578, 2010. [24] L. Leyland, P.Batra, F. Wong, and R. Llewelyn, “A retrospective evaluation of the eruption of impacted permanent incisors after extraction of supernumerary teeth,” Journal of Clinical Pediatric Dentistry, vol. 30, no. 3, pp. 225–232, 2006. [25] M. Ashkenazi, B. P. Greenberg, G. Chodik, and M. Rakocz, “Postoperative prognosis of unerupted teeth after removal of supernumerary teeth or ,” American Journal of Orthodontics and Dentofacial Orthopedics, vol. 131, no. 5, pp. 614–619, 2007. Hindawi Publishing Corporation International Journal of Dentistry Volume 2012, Article ID 540561, 7 pages doi:10.1155/2012/540561

Review Article Oral Leukoplakia as It Relates to HPV Infection: A Review

L. Feller and J. Lemmer

Department of Periodontology and Oral Medicine, University of Limpopo, Medunsa Campus, Medunsa, South Africa

Correspondence should be addressed to L. Feller, [email protected]

Received 13 July 2011; Revised 2 September 2011; Accepted 19 December 2011

Academic Editor: Neil S. Norton

Copyright © 2012 L. Feller and J. Lemmer. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Leukoplakia is the most common potentially malignant lesion of the oral cavity and can be categorised according to its clinical appearance as homogeneous or nonhomogenous. Tobacco and areca nut use, either alone or in combination are the most common risk factors for oral leukoplakia, but some oral leukoplakias are idiopathic. Some leukoplakias arise within fields of precancerized oral epithelium in which the keratinocytes may be at different stages of cytogenetic transformation. Leukoplakias may unpredictably regress, may remain stable, or may progress to carcinoma. There is a greater risk of carcinomatous transformation of idiopathic leukoplakia, of non-homogenous leukoplakia, of leukoplakia affecting the floor of the mouth; the ventrolateral surface of the and the maxillary retromolar and adjoining soft palate (collectively called high-risk sites), of leukoplakia with high-grade epithelial dysplasia, and of leukoplakia in which the keratinocytes carry cytogenetic alterations associated with carcinomatous transformation. Although there appears to be some link between human papillomavirus (HPV) and oral leukoplakia, there is little evidence to support a causal relationship either between HPV infection and oral leukoplakia or between HPV-infected leukoplakic keratinocytes and their carcinomatous transformation.

1. Introduction oral leukoplakia, but there is little evidence of a causal relationship between either HPV infection or alcohol, and Leukoplakia is the most common potentially malignant oral leukoplakia [6]. lesion of the oral cavity [1, 2]. Leukoplakia is a term describ- It has been suggested that a definitive diagnosis of ing “a white lesion of the oral mucosa that cannot be char- oral leukoplakia must be established by histopathological acterized clinically or microscopically as any other defined exclusion of other keratotic oral lesions that are recognised oral entity” [3, 4]. At a World Health Organisation as specific entities, and by exclusion of any aetiological agents (WHO) workshop held in 2005, it was recommended that other than tobacco/areca nut use [7]. oral leukoplakia be defined as “a white plaque of questionable risk having excluded (other) known diseases or disorders that It is the opinion of the authors that these criteria are carry no increased risk for cancer” [5–7]. Oral leukoplakia unrealistically limiting, ignoring as they do the possible needs to be distinguished from other predominantly white roles of HPV, alcohol, chronic inflammation, and low- keratotic lesions including frictional keratosis and grade chronic frictional trauma in the pathogenesis of oral leukoplakia. Referring to the WHO definition of 2005 above, nicotina, which do not have malignant potential [1, 2, 5–8]. ffi About 70–90% of oral leukoplakias are related to smok- it is di cult to understand how such a definition could ing and areca nut use, either alone or in combination, and gain any useful currency since it is so “exclusive” that it there is a direct relationship between the frequency and leaves no rational guidance for the everyday diagnosis of oral the duration of cigarette, pipe, or cigar smoking and the leukoplakia. prevalence of oral leukoplakia [8, 9]. The factors implicated in the pathogenesis of idiopathic leukoplakia are unknown. 2. Oral Leukoplakia: Clinical Aspects However it is possible that infection of the oral epithe- lium with human papillomavirus (HPV) and excessive According to its clinical appearance, oral leukoplakia can consumption of alcoholic beverages may be associated with be categorised into two main clinical types: homogeneous 2 International Journal of Dentistry and non-homogeneous. Either type may occur as an isolated [27]. This is not easy to explain. Bearing in mind that the lesion or as multiple lesions. The leukoplakic lesion can vary study was on histopathological material, an explanation may in size from a few millimetres to several centimeters [1, 2, 5– be that blacks tend to postpone seeking medical treatment 12]. until the leukoplakia has already undergone carcinomatous Homogeneous leukoplakia is a uniformly white flat transformation, thus skewing the statistics away from the plaque with a smooth or relatively smooth surface; non- leukoplakia [27], or because black people in South Africa homogeneous leukoplakia may be nodular or verrucous may smoke less than white people. having a wrinkled or corrugated surface or may be a mingling of white and red areas termed erythroleukoplakia [7, 10, 11]. 4. Epithelial Dysplasia and Oral Leukoplakia The clinical appearance of oral leukoplakia may change over time. Some homogeneous lesions may become larger, or The reported prevalence of epithelial dysplasia in oral leuko- non-homogeneous, but most oral leukoplakias will remain plakia ranges from 5% to 25% [8]. Dysplasia is more frequent stableorwillregress,whilesomefewwillundergocarcino- in non-homogeneous than in homogeneous leukoplakia matous transformation [13–15]. [11], and it is probable that dysplasia is the histopathological Oral , of all precancerous oral lesions, expression of genomic and molecular alterations in a field of carries the greatest threat of malignant transformation. It keratinocytes [28, 29]. has a velvety-red appearance, and about 50% of all cases The presence of epithelial dysplasia is a marker of the of erythroplakia are already squamous cell carcinomata at malignant potential of oral leukoplakia, and the risk of the time of diagnosis. The erythroplakic component of oral an individual leukoplakic lesion to progress to carcinoma erythroleukoplakia is identical to erythroplakia [16]. increases with the increase of the grade of the epithelial Proliferative verrucous leukoplakia, considered to be dysplasia [11, 12, 14, 30]. either a clinical subtype of non-homogeneous oral leuko- However, some dysplastic oral leukoplakias can remain plakia or to be a distinct clinical entity, is not strongly associ- stable or even regress, while some oral leukoplakias without ated with smoking, is characterized by multiple leukoplakic epithelial dysplasia will indeed progress to carcinoma [5, lesions that affect wide areas of the oral epithelium, and may 11, 12]. In one study 36% of dysplastic oral leukoplakias progress either to or to squamous cell progressed to squamous cell carcinoma, but a substantial carcinoma [17–20]. In most cases, proliferative verrucous proportion of 16% of oral leukoplakias without epithelial leukoplakia is recognised only late in its course since in its dysplasia at the time of initial biopsy also progressed to initial stages it is identical to an isolated leukoplakia [17–24]. carcinoma [31]. The risk of progression to carcinoma of leukoplakias with moderate and severe dysplasia is estimated 3. Epidemiology of Oral Leukoplakia to be twice as great as for oral leukoplakias with simple epithelial hyperplasia or with mild dysplasia [14]. The data from epidemiological studies on oral leukoplakia Treatment of dysplastic oral leukoplakia by excision, by is inconsistent, most probably owing to differences in case laser or by cryosurgery, or by topical or systemic chemo- selection criteria (house-to-house surveys, hospital surveys, therapy does not eliminate either the risk of relapse or age, gender, race, ethnicity, and tobacco use) and in method- recurrence, or the risk of carcinomatous transformation ology (diagnostic criteria, time of follow-up and whether or [1, 5, 6]. The estimated recurrence rate of oral leukoplakia not the leukoplakia had previously been treated) [1, 10, 11]. maybeashighas30%[32], and squamous cell carcinoma Estimates of the global prevalence of oral leukoplakia develops at 12% of sites of treated leukoplakia [15]. In a study range from 0.5% to 3.46%, and of the rates of carcinomatous investigating the pattern of carcinomatous transformation of transformation of oral leukoplakia from 0.7% to 2.9% [25]. oral leukoplakia and oral erythroplakia, 36% of carcinomata Oral leukoplakia is more prevalent in India where persons developed at the same site, 49% at contiguous sites, and 15% smoke and practice the habit of tobacco and areca nut at oral sites remote from the preexisting lesions [33]. chewing more than elsewhere [26]. It is evident from this data that some cases of treated Oral leukoplakia is usually diagnosed in middle age, and oral leukoplakia are unpredictably destined to recur or its prevalence increases with age. About 10% of oral leuko- to undergo carcinomatous transformation, and that there plakias are idiopathic and the greater part of the remaining are not yet any diagnostic methods available (clinical, 90% is associated with the use of tobacco/areca nut [26]. histological or molecular), to confidently identify these cases Males are more often affected than females probably owing [1]. to the greater prevalence of tobacco use by males [8]. The Epithelial dysplasia in oral leukoplakia is a useful marker buccal mucosa is affected in 25% of cases, the mandibular of the risk of carcinomatous transformation and is an impor- gingiva in 20%, the tongue in 10%, the floor of the mouth in tant guide to clinical management [1, 11, 28]. However, since 10%, and other oral sites account for the remainder [13]. dysplasia can remain stable for long periods, it cannot be The literature on the relationship between race and oral used with confidence as a predictor of carcinomatous trans- leukoplakia is sparse. In a South African study of archived formation [14, 29]. Moreover, as the histological exercise of histopathological material, 86% of oral leukoplakias were grading of epithelial dysplasia is highly subjective with low from whites, 9% from blacks, and 5% from Asians, despite interpersonal and intrapersonal reproducibility [16, 34, 35], the fact that the vast majority of South Africans are black and as an incisional biopsy cannot be representative of an International Journal of Dentistry 3 entire lesion [34, 36], a histopathological report of any degree and is associated with carcinomatous transformation of of epithelial dysplasia or of the absence of epithelial dysplasia these lesions [33, 41, 42, 44, 45]. Additional cytogenetic must be viewed with caution. alterations to the keratinocytes in the precancerized field referred to above may result in the evolution of one or several keratinocytes containing a complete set of cytogenetic 5. The Natural Course and the Malignant alterations of a cancerous phenotype, and in the subsequent Potential of Oral Leukoplakia development of squamous cell carcinoma [41, 46, 47]. However, some precancerous oral leukoplakias in which The progression of oral leukoplakia to carcinoma is unpre- cytogenetic alterations in the keratinocytes cannot be dictable but is relatively infrequent with an estimated overall demonstrated, nevertheless undergo carcinomatous trans- risk of less than 2% per year [5, 6, 13, 26]; if progression formation [41, 42]. The pathogenic mechanisms that bring occurs, it may take a few months or many years [8]. The about the progressive transformation of these keratinocytes carcinomatous transformation of oral leukoplakia is not predictably associated with tobacco smoking [33], and the to carcinomatous cells are yet to be elucidated. Most oral frequency of carcinomatous transformation of idiopathic leukoplakias are benign in nature and will remain stable leukoplakia is higher than that of tobacco-associated leuko- or will regress [28, 32]. These leukoplakias probably have ff plakia [11, 26]. adi erent aetiopathogenesis to precancerous leukoplakias In populations where smoking, the use of smokeless and probably do not have the cytogenetic characteristics of tobacco, reverse smoking, and the use of areca nut are precancerous leukoplakias. What is certain, however, is that very prevalent, most squamous cell carcinomata arise from leukoplakias with malignant potential and those without preexisting leukoplakias; while in populations with a lower malignant potential cannot be distinguished clinically [1]. prevalence of these habits, most squamous cell carcinomata arise de novo in normal-looking epithelium [26]. It has been suggested that squamous cell carcinoma arising de 6. Human Papillomavirus and Oral Leukoplakia novo usually runs a more aggressive course and has a less Human papilloma viruses (HPVs) are strictly epitheliotropic favourable prognosis than squamous cell carcinoma arising and infect either cutaneous or mucosal squamous epithe- from preexisting leukoplakia [12, 26], but a recent study lium, depending upon their genotype [48, 49]. Those that has demonstrated little difference [37]. Sometimes squamous infect mucosal epithelium have been categorized into high- cell carcinoma arises de novo in close proximity to oral risk types (e.g., HPV-16, 18, 31, 33, and 35) based on their leukoplakias [8]. epidemiological association with carcinoma of the cervix Non-homogeneous leukoplakia has a greater risk of car- uteri, or into low-risk types (HPV-6, 11, 13, and 32) [50]. cinomatous transformation (20–25%) than homogeneous These categories have been universally adopted for use in leukoplakia (0.6–5%) [11, 13]. Most leukoplakias either studies of the oncogenic significance of HPV infection at all remain stable or will regress [13, 15]. However, if proliferative anatomical regions of the upper aerodigestive tract. verrucous leukoplakia is considered as a distinct entity, most such cases progress to carcinoma [18, 24]. Low-risk HPV genotypes have been implicated in the The rates of progression of large oral leukoplakias pathogenesis of the benign oral proliferative epithelial (>5 mm) and of leukoplakias at sites in the mouth known lesions, squamous cell papilloma, common wart (verru- to be at most risk of developing carcinoma (floor of cous vulgaris), condyloma acuminatum, and focal epithe- mouth, ventrolateral surface of tongue, and maxillary lial hyperplasia (Heck disease); while high-risk types have retromolar/soft palate region) are greater than for smaller been associated with precancerous and cancerous oral and leukoplakias or for leukoplakias at other sites in the mouth oropharyngeal epithelial lesions [49, 51–56]. [1, 11, 13, 33, 38]. The increased risk of carcinomatous There is an extreme variation in the reported prevalence transformation of oral leukoplakia at high-risk sites is not of HPV infection in oral precancerous and cancerous lesions entirely a function of the degree of dysplasia. It is also ranging from 0% to 100% [57, 58]. This is owing to dependentuponasyetundefinedcharacteristicsofthe differences in sampling and HPV detection methods, to location of the leukoplakia since the rate of carcinomatous differences in ethnicity, geographic locations, and sample size transformation of dysplastic leukoplakias at high-risk sites is of the subjects examined, and to the inappropriate group- greater than the rate of transformation of equally dysplastic ing together of different lesions from different anatomical leukoplakias at other sites [38]. locations of the mucosa of the upper aerodigestive tract There is evidence that clearly suggests that some leuko- [49, 51, 58–64]. plakias arise from cytogenetically altered transformed ker- Many studies investigating the association of HPV and atinocytes within fields of precancerized oral epithelium. squamous cell carcinoma of the mucosa of the upper Keratinocytes of oral leukoplakia show cytogenetic changes aerodigestive tract used PCR techniques for detection of including alterations in the p53 tumour suppressor gene, HPV DNA without also quantifying the DNA viral load. aberrations in their DNA content, and loss of heterozy- PCR can detect extremely small fragments of DNA that may gosity (LoH) at chromosomal regions of candidate tumour represent either contamination of the sample or biologically suppressor genes [20, 33, 39–45].LoHateither3porat insignificant HPV infection [51, 57, 58]. These findings have 9p occurs frequently in keratinocytes of oral leukoplakia been reported as if they were pathogenically significant. 4 International Journal of Dentistry

Whether these are legitimate findings or are the results that do not express E6/E7 mRNA, E6/E7 oncoproteins may of inconsistencies and errors in methodology, several HPV well have participated or have had a complementary role in genotypes have been detected in precancerous oral lesions. the initial transformation, but then phased out [77]. High-risk HPV genotypes, in particular HPV-16, have been With oropharyngeal carcinoma as the model, a causal reported to be the most prevalent in oral leukoplakias, association between HPV and cancerization in oral epithe- including proliferative verrucous leukoplakia [55, 65]. Other lium is likely if the cells of the lesion contain HPV DNA reports implicated low-risk rather than high-risk HPV expressing E6 and/or E7 mRNA [71], if there is viral genotypes in oral leukoplakia [54, 63], and yet others assert integration within the cellular genome [74], and if there is that oral leukoplakia is coinfected with a variety of HPV a high viral load (>1 copies per cell). A limited biological genotypes [49, 55, 66]. In a meta-analysis of data from 94 significance of the virus in the process of transformation studies of a total of 4580 specimens, Miller and Johnstone can be deduced if there is a low-copy number (<1copyper [63] determined that the likelihood of HPV being detected cell), or if there is no transcriptional activity of E6 and/or in precancerous oral lesions is 2 to 3 times greater and in E7 mRNA [60, 71]. Nevertheless, although integration of oral squamous cell carcinoma is 4 to 5 times greater than HPV DNA into the cellular genome is a strong indication of in normal oral mucosa. The prevalence of HPV in normal the oncogenic potential of the virus, transcription of HPV- oral mucosa, in nondysplastic leukoplakias, in dysplastic 16 E6/E7 mRNA has been shown to occur in oropharyngeal leukoplakias and in other precancerous intraepithelial oral carcinoma without integration of viral DNA, the virus being neoplasms, and in oral squamous cell carcinoma is likely to in an episomal form [69]. be 10%, 20.2%, 26.2%, and 46.5%, respectively [63]. It is well established that non-homogeneous leukoplakias This suggests that there may be some link between HPV more frequently undergo malignant transformation than infection and oral precancerous and cancerous lesions. As homogeneous leukoplakias, yet it appears that HPV is E6 and E7 oncoproteins of high-risk HPV genotypes have found more commonly in homogeneous than in non- the capacity to mediate carcinomatous transformation of homogeneous leukoplakia [54, 78]. Nevertheless the role infected keratinocytes by inactivating cellular p53 and Rb of HPV in the pathogenesis of oral leukoplakia and in its tumour suppressor pathways [50, 52], HPV may play either progression to carcinoma is unclear since there is a low viral an oncogenic or a co-oncogenic role in some HPV-infected load in HPV-cytopositive precancerous and cancerous oral precancerous and cancerous epithelial neoplasms. lesions, and viral integration is seldom found [72, 76]. It In fact, HPV-16 has been found to be causally associated is possible that HPV DNA in oral leukoplakia and in oral primarily with squamous cell carcinoma of the palatal tonsils squamous cell carcinoma may be oncogenically insignificant. [67–70] in a subset of subjects who are younger, consume Alternatively the HPV may have superinfected keratinocytes less tobacco, are more engaged in high-risk sexual behaviour already initially transformed and may thus additively or (great number of lifetime sexual partners and practicing synergistically promote later stages of transformation [49, 51, oral-genital sex), have higher HPV-16 serum antibody titers, 69]. and have a better disease-free survival and overall survival Little is known about the E6 and E7 proteins of low- rates than subjects with HPV-cytonegative oropharyngeal risk HPV either with regard to their role in the patho- squamous cell carcinoma [51, 64, 67–70]. The cells of HPV- genesis of HPV-infected oral leukoplakias, or with regard cytopositive oropharyngeal carcinoma in these subjects have a distinct molecular profile [50]. The cells of squamous to their role in the carcinomatous transformation of some cell carcinoma causally associated with HPV express E6/E7 leukoplakias. It is possible that as in other HPV-associated oncoproteins. They frequently demonstrate viral integration benign proliferative oral epithelial lesions, E6 and E7 proteins within the cellular genome with the presence of intact of low-risk HPV types found in oral leukoplakia may E6 gene. They exhibit high viral load, reduced expression stimulate suprabasal postmitotic infected keratinocytes to of Rb proteins, functional overexpression of p16 INK4A, reenter the S-phase of the cell cycle resulting in epithelial unmutated p53 gene, and loss of heterozygosity (LoH) at proliferation and disturbed maturation, without causing the chromosomal loci 3p, 9p and 17p is infrequent [51, 68– genomic instability possibly associated with subsequent cell 74]. In contrast, HPV-cytonegative oropharyngeal squamous transformation. This mechanism may be a co-determinant of cell carcinoma is characterized by p53 gene mutations, by the development of the leukoplakia, but there is no concrete frequent LoH at 3p, 9p, and 17p, by decreased levels of evidence to support this. p16INK4A and by normal or increased levels of Rb proteins [50, 51, 71]. 7. Treatment Recent meta-analyses and comprehensive studies [60, 62, 67, 75] show little or no causal association between HPV As oral leukoplakia is potentially malignant, and as some and oral squamous cell carcinoma in contrast to the strong leukoplakias will unpredictably progress to carcinoma, ide- association between HPV and oropharyngeal squamous cell ally all oral leukoplakias should be treated. When dealing carcinoma.HPV-16cytopositiveoralsquamouscellcarci- with two or three accessible circumscribed lesions, the treat- is characterized by a low viral load, by infrequent viral ment of choice is surgical excision. For multiple or for large integration, and the cancerous cells seldom contain active leukoplakias where surgical treatment would be impractical transcriptional E6/E7 mRNA [72, 76]. However, it is possible because it would result in unacceptable deformities or in that, in HPV-cytopositive oral squamous cell carcinomata functional disabilities, treatment can be by cryosurgery, International Journal of Dentistry 5 laser surgery, or by the use of topical bleomycin. However, [7] S. Warnakulasuriya, N. W. Johnson, and I. van der Waal, regardless of the extent of the lesion or of the modality of “Nomenclature and classification of potentially malignant treatment, in as many as 30% of treated cases, leukoplakias disorders of the oral mucosa,” Journal of Oral Pathology and will recur and treatment will not prevent the progression of Medicine, vol. 36, no. 10, pp. 575–580, 2007. some leukoplakias to squamous cell carcinoma [5, 15, 21, [8] B. Neville, D. Damm, C. Allen, and J. 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Khammissa et al., “Epidemiol- planus,” Oral Surgery, Oral Medicine, Oral Pathology, Oral ogy and transmission of HPV infection: vaccination for HPV Radiology and Endodontology, vol. 98, no. 6, pp. 705–711, infection,” South African Dental Journal, vol. 65, pp. 478–481, 2004. 2010. [65] J. M. Palefsky, S. Silverman Jr., M. Abdel-Salaam, T. E. Daniels, and J. S. Greenspan, “Association between proliferative ver- rucous leukoplakia and infection with human papillomavirus type 16,” Journal of Oral Pathology and Medicine, vol. 24, no. 5, pp. 193–197, 1995. [66] M. Bouda, V. G. Gorgoulis, N. G. Kastrinakis et al., ““High risk” HPV types are frequently detected in potentially malig- nant and malignant oral lesions, but not in normal oral mucosa,” Modern Pathology, vol. 13, no. 6, pp. 644–653, 2000. [67] J. Pintos, M. J. Black, N. Sadeghi et al., “Human papillo- mavirus infection and oral cancer: a case-control study in Montreal, Canada,” Oral Oncology, vol. 44, no. 3, pp. 242–250, 2008. 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[71]B.J.M.Braakhuis,P.J.F.Snijders,W.J.H.Keuneetal., “Genetic patterns in head and neck cancers that contain or lack transcriptionally active human papillomavirus,” Journal Hindawi Publishing Corporation International Journal of Dentistry Volume 2012, Article ID 125036, 4 pages doi:10.1155/2012/125036

Clinical Study Technical Considerations in Rehabilitation of an Edentulous Total Glossectomy Patient

Pravin Bhirangi, Priyanka Somani, K. P. Dholam, and Gurmeet Bachher

Department of Dental and Prosthetic Surgery, Tata Memorial Hospital, Mumbai 400 012, India

Correspondence should be addressed to Pravin Bhirangi, [email protected]

Received 5 July 2011; Accepted 14 December 2011

Academic Editor: Pilar Hita-Iglesias

Copyright © 2012 Pravin Bhirangi et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

The technician by virtue of his profession plays an important role in fabricating silicone tongue prosthesis for a total glossectomy patient. The technician, with his skills and specialized knowledge in handling material, plays a valuable role as a member of the oncology team. A patient with total glossectomy can be rehabilitated by silicone tongue prosthesis as an aid to improve his speech and swallowing. This paper describes the technical steps involved in fabricating a silicone tongue prosthesis for an edentulous total glossectomy patient.

1. Introduction excision of the tongue and completely edentulous state of the upper and lower jaws, tongue prosthesis was planned for the Oncologic management of advanced carcinoma of the patient (Figures 1 and 2). tongue is a difficult medical problem that can create serious treatment dilemmas. Often criticized as a treatment option because of the severe functional sequelae, total glossectomy 2. Procedure may sometimes be the treatment of choice. Step 1. Mucocompressive impression was made of an upper Tongue prosthesis occupies the space in the floor of edentulous arch using impression compound and mucostatic the oral cavity. It provides the patient with a platform for impression was made of lower edentulous arch and floor directing food into the esophagus and aids in speaking. of the mouth using irreversible hydrocolloid impression This paper describes the technical steps involved in material by a maxillofacial prosthodontist. The disinfected prosthetic management of an edentulous patient (EP) who impressions were then sent to the dental laboratory. underwent total glossectomy with a prosthesis made of silicone tongue (fabricated with molloplast-B) attached to Step 2. The diagnostic casts/primary casts were obtained. mandibular complete denture. Custom trays were fabricated on upper and lower edentulous EP reported with ulceroproliferative growth on tongue primary casts with autopolymerizing acrylic resin. (T4N2aMx). He underwent near total glossectomy with modified neck dissection with pectoralis major myocu- Step 3. Border molding using low fusing impression com- taneous flap reconstruction. Postoperatively, he received pound was done, and secondary impressions of upper and radiotherapy (4600 Gy) only. lower edentulous arch with zinc oxide eugenol impression The patient complained of difficulty in eating and paste using selective pressure impression technique were swallowing with no complaint of aspiration. He was on liquid made (Figure 3). Stock tray was then used to make a pick-up diet without ryles tube. After completion of one year of impression of this (only mandibular arch) and to record floor radiation, the intraoral tissues healed to withstand prosthetic of the mouth together as a single impression (irreversible intervention on clinical examination. In view of total surgical hydrocolloid impression). 2 International Journal of Dentistry

Figure 3: Final Impression.

Figure 1: Preoperative intraoral view.

Figure 4: Wax up trial of tongue prosthesis.

Figure 2: Preoperative extraoral view.

Step 4. The impressions were disinfected and poured with type III dental stone to obtain master cast.

Step 5. On the master cast, temporary record bases were Figure 5: Wax up trial of tongue prosthesis in the patient’s mouth. made using autopolymerizing acrylic resin, which were tried in patient’s mouth to check retention and stability.

Step 6. On the temporary record bases, occlusal rims were made to record maxilla-mandibular relation and the teeth arrangement was done following recording of jaw relation.

Step 7. Wax up of tongue prosthesis [1] was done on the temporary record bases, which was contoured in the shape of a tongue that conforms to oral cavity dimensions with rounded edges (Figure 4). The tongue tip was arched inferiorly to approximately a 15-degree angle, and the entire pattern was then arched slightly to form the highest point at the anterior one third. Wax pattern was then folded to form a wide central V-shaped angle (approximately 160 degrees). The wax was reduced 4 to 5 mm of thickness at the base and the posterior Figure 6: Flasking of the tongue prosthesis. two thirds. International Journal of Dentistry 3

Figure 7: Dewaxing of the tongue prosthesis. Figure 9: Packing of heat cure acrylic resin.

Figure 8: Packing of Molloplast-B material.

Figure 10: Final tongue prosthesis.

The wax pattern was finally sealed to the lower trial denture. 3. Discussion Step 8. The waxed up prosthesis was then tried in patients mouth. (Figure 5) The speech therapist evaluated the speech Swallowing and speaking by prosthodontic management of articulation with the waxed up tongue (WT) for maximum glossectomy patient is a difficult undertaking for both the contact of the dorsum with palate for optimum articulation. prosthodontist and the patient. Particular considerations should be given to the patient’s chief complaints when Step 9. Processing of silicone tongue prosthesis: flasking planning treatment for the glossectomy patient. A patient and dewaxing was done for the waxed up upper and lower may be able to accommodate to some dysfunction without prosthesis in conventional manner (Figures 6 and 7). prosthetic support, while desiring prosthetic treatment helps At the packing stage, the heat temperature vulcaniz- to improve or correct other specific problems [2]. ing silicone (Molloplast-B, Regneri GmbH & Co.KG, W- A wide buccolingual table, an occlusal table height Germany) was packed in tongue space (Figure 8). matched to that of the tongue body, and a closely adhering Trial closure was done and excess molloplast material was tongue and lingual flange are effective means of preventing removed. the food from dropping to the oral floor, keeping the food Heat cure denture base resin was packed in edentulous on the occlusal table, and crushing the food. ridge space (Figure 9). When constructed in a systematic manner with the The flask was closed and kept for overnight bench curing. assistance of a speech pathologist, the mandibular tongue Curing of the prosthesis was done as per manufacturer prosthesis can achieve the following [3]: instructions. After deflasking, the prosthesis was trimmed, finished, (1) reduction in the size of the oral cavity, thereby and polished (Figures 10 and 11). improving resonance characteristics, 4 International Journal of Dentistry

Figure 11: Final tongue prosthesis.

Figure 13: Postoperative extraoral view.

4. Summary

Figure 12: Tongue prosthesis in the patient’s mouth. The paper describes technical steps for the prosthetic rehabilitation of an edentulous glossectomy patient, in which treatment dentures were constructed with mandibular tongue prosthesis and the appropriate denture form and (2) direction of food into the esophagus with the aid of a occlusion was established. trough carved into the prosthetic tongue, The prosthetic tongue may not replace the intricately (3) protection of the underlying fragile tissue, mobile structure of the tongue, which is capable of infinite movements in swallowing and speech. The silicone tongue (4) development of a surface for the residual tongue prosthesis does provide glossectomy patient with a certain tissue to contact during speech and swallowing, degree of comfort and function. (5) improvement in appearance and psychosocial adjust- ment. References

In this EP, after fabrication of the tongue prosthesis swal- [1] K. Izdebski, J. C. Ross, W. L. Roberts, and R. G. de Boie, lowing improved. Liquid diet was replaced with semisolids “An interim prosthesis for the glossectomy patient,” Journal of ffi without di culty and apparent aspiration (Figures 12 and Prosthetic Dentistry, vol. 57, no. 5, pp. 608–611, 1987. 13). [2] M. A. Pigno and J. J. Funk, “Prosthetic management of a total Improvement in speech was also observed. Without glossectomy defect after free flap reconstruction in an edentu- tongue prosthesis, he was substituting labiodentals and vow- lous patient: a clinical report,” Journal of Prosthetic Dentistry, els for fricative and palatal sounds. After using prosthesis for vol. 89, no. 2, pp. 119–122, 2003. six months, fricative and palatal sounds improved audibly. [3]M.A.Aramany,J.A.Downs,Q.C.Beery,andY.Aslan,“Prost- The material used to fabricate tongue prosthesis, sili- hodontic rehabilitation for glossectomy patients,” Journal of cone (Molloplast-B, Molloplast, Regneri GmbH @ Co, W- Prosthetic Dentistry, vol. 57, pp. 608–111, 1987. Germany), permanent soft relining material, has several [4]M.A.Aramany,J.A.Downs,Q.C.Beery,andY.Aslan,“Prost- advantages [4]: hodontic rehabilitation for glossectomy patients,” The Journal of Prosthetic Dentistry, vol. 48, no. 1, pp. 78–81, 1982. (i) single component, ready to use eliminating mixing and dosing errors, (ii) easy processing, (iii) can be polymerized simultaneously with acrylic, (iv) stands the influences of oral environment without deterioration, (v) nonirritant and tissue compatible, (vi) odourless and tasteless. Hindawi Publishing Corporation International Journal of Dentistry Volume 2011, Article ID 321750, 5 pages doi:10.1155/2011/321750

Review Article Cell Transformation and the Evolution of a Field of Precancerization As It Relates to Oral Leukoplakia

L. Feller and J. Lemmer

Department of Periodontology and Oral Medicine, University of Limpopo, Medunsa Campus, South Africa

Correspondence should be addressed to L. Feller, [email protected]

Received 13 July 2011; Accepted 10 August 2011

Academic Editor: Paul C. Edwards

Copyright © 2011 L. Feller and J. Lemmer. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Potentially malignant oral leukoplakias arise within precancerized epithelial fields consisting of cytogenetically altered keratinocytes at various stages of transformation. The evolution of a clone of keratinocytes culminating in a precancerous phenotype is a function of the number of mutagenic events, rather than the sequential order in which they occur. The altered molecular configurations of the transformed precancerous keratinocytes may confer upon them a growth advantage in relation to the unaltered neighbouring keratinocytes. Replicative clonal expansion of these keratinocytes results in the progressive replacement of the surrounding normal keratinocytes by the fitter clone or clones of altered cells. The precancerized oral epithelial field may have a clinically normal appearance and microscopically may be normal or may show dysplasia. Oral leukoplakias arising within a precancerized epithelial field in which the keratinocytes show DNA aneuploidy or loss of heterozygosity at certain specific chromosomal loci have the potential to progress to carcinoma. The pathogenic mechanisms that drive the carcinomatous transformation of oral leukoplakias, in which cytogenetic alterations in the keratinocytes cannot be detected, are unknown.

1. Introduction 2.AnOralFieldofPrecancerization The genome can sustain a number of alterations to its DNA A field of precancerized oral epithelium comprises a large without any apparent cellular functional disability, but any number of cytogenetically altered keratinocytes at various cell that has sustained a critical number of DNA alterations, stages of transformation. It is not yet clear how many genetic such that one or two additional alterations are likely to result events are necessary to establish cellular transformation, in malignant change, is regarded as being transformed. and not all the molecular alterations associated with field Itisevidentthatpotentiallymalignantoralleuko- precancerization of normal-looking oral epithelium have plakias arise within fields of precancerization consisting been characterized [1]. of cytogenetically altered keratinocytes [1, 2]. A field of The initial transformational events occur in progenitor precancerization in the oral cavity can be defined as an cellsinthebasaland/orparabasalcelllayersoftheoral area of clinically normal-looking epithelium which is either epithelium [10, 11]. These progenitor cells give rise to microscopically normal or shows dysplasia, but in which cells that maintain the integrity of the basal and parabasal some keratinocytes have undergone cytogenetic alterations cell layers and to amplifying cells that divide frequently, [1–8]. The process of progressive cytogenetic alteration producing daughter cells that enter the maturation process, (transformation) can confer upon the keratinocytes in such and gradually progress to the surface of the epithelium [12]. an epithelial field a growth advantage in relation to the The initial cytogenetic events leading to cell trans- normal surrounding keratinocytes [9] so that within an formation are most probably characterized by molecular apparently clinically normal stretch of oral mucosa there can and subsequent functional alterations to genes maintaining be a pathobiological continuum from normal epithelium to the cell’s genomic stability. Such alterations precipitate precancerized epithelium where carcinoma can arise [7]. sequential cytogenetic lesions driving the genetic evolution 2 International Journal of Dentistry of the initially transformed progenitor cell towards a cell The precancerous field may be clinically normal, whether with a complete set of genetic alterations of a malignant or not there is epithelial dysplasia. The presence of a field phenotype [13–17]. In this regard, the evolution of a of precancerization may be disclosed by the development cancerous keratinocyte is the outcome of a sufficient number of a leukoplakia or of an erythroplakia, or the appearance of accumulated cytogenetic alterations rather than of the of squamous cell carcinoma will make the nature of the sequential order in which they occur [15, 18–20]. previously unrecognized field of precancerization become all The cytogenetic alterations in precancerous keratinocytes too apparent [1]. reflect a noncritical accumulation of molecular events, and The cytogenetic events culminating in the development those seen in cancerous keratinocytes are the outcome of a field of precancerization can be either spontaneous of a further critical accumulation of transforming events. or microenvironmentally induced, or extraneously imposed, The exact sequence of the cytogenetic molecular events but it is possible that some ectodermal stem cells destined culminating in carcinogenesis can vary [14, 21]. to become progenitor cells in the oral epithelium can Most of the cytogenetic and transcriptional alterations actually undergo genetic and/or epigenetic alterations during occur early in the continuum from normality, to precancer- organogenesis, giving rise to cytogenetically altered epithelial ization, to carcinoma. It is probable that a greater number progenitor cells. If during maturation these developmentally of such alterations are required for the transformation of a altered keratinocytes are exposed to further transforming normal to a precancerous keratinocyte, than for the trans- formation of a precancerous keratinocyte to a keratinocyte molecular events, their clonal expansion can culminate in the expressing a full cancerous phenotype [22]. formationofaprecancerizedfield[1, 10, 11, 25, 30]. The number of sequential cytogenetic alterations nec- It is possible that dysregulation of gene expression in the essary for a progenitor cell to become a cancer cell is fibroblasts of the lamina propria, with consequent produc- imponderable, but is estimated to be between 3 and 12. tion and release of aberrant mediators, may impose upon The exact number of these singular genetic events is a the overlying keratinocytes that have already undergone function of several factors: loss of DNA repair mechanisms, initial transformation from whatever cause, dysregulatory dysregulation of signal transduction pathways, and blocking inductive signals contributing to the development of the of mechanisms leading to apoptosis [23, 24], which together precancerized field [1, 31–33]. will selectively confer an advantage upon the transformed cells with regard to competitive fitness and growth in relation to the surrounding normal cells [9]. This cytogenetic evolu- tion will promote the clonal expansion of the transformed cell population and their subsequent clonal divergence to 3. The Failure of the Studies of form either a single precancerized epithelial field or multiple Potentially Malignant Lesions to Contribute fields that may be contiguous with or separate from each to Knowledge of Potentially Malignant other, at the expense of the surrounding normal epithelium Lesions of the Mouth [1]. A field of precancerization may comprise a monoclonal There are a number of potentially malignant lesions of cell population originating from one transformed progenitor the upper aerodigestive tract in which the oral cavity, basal cell that underwent clonal expansion, and spread later- nasopharynx, oropharynx, hypopharynx, and the larynx, ally. The molecular profile of the transformed keratinocytes are grouped together as if premalignancies of these sites in such a field may be identical if they are all part of constitute a homogeneous group. Potentially malignant a monoclone. On the other hand, the molecular profile lesions from these various sites are, however, site specific, so of the transformed keratinocytes may be similar to but such studies are of limited value in isolating molecular and not identical with one another (clonally related) if they cytogenetic markers of carcinomatous transformation of oral arose from subclones related by descent from the original leukoplakia [1]. monoclone, but each subclone having experienced episodes of different mutations [1, 25–29]. Furthermore, although the potentially malignant lesions However, a field of precancerization may also consist of of the upper aerodigestive tract have common histological a polyclonal cell population, several transformed progenitor features of epithelial dysplasia or hyperplasia, they certainly basal cells having undergone independent clonal expansion do not have similar clinical features or natural courses. In with subsequent independent clonal divergence. The molec- addition, in several studies, oral epithelial dysplasia and ular profiles of the transformed keratinocytes in such a hyperplasia have been chosen as the inclusion criteria for field will be dissimilar, but might share some cytogenetic categorising oral lesions as being potentially malignant, ff alterations, as the polyclonal cells will have been exposed to without di erentiating the clinical entities. Moreover, certain identical carcinogens and to the same microenvironment in reactive and inflammatory lesions of the oral mucosa exhibit- the mouth. Thus, the keratinocytes of a unique precancerous ing epithelial hyperplasia or low-grade dysplasia have been oral leukoplakia or of a unique oral squamous cell carcinoma erroneously included in some of the studies although these can show molecular heterogeneity with similar or dissimilar lesions will never undergo carcinomatous transformation cytogenetic alterations [1, 25–29]. [1]. International Journal of Dentistry 3

4. Molecular Markers of Oral Leukoplakia and keratinocytes manifesting aneuploidy have a lower rate of Its Progression to Squamous Cell Carcinoma survival compared to subjects with oral squamous cell carcinoma evolving from dysplastic leukoplakia with ker- The development of precancerous oral leukoplakia and its atinocytes with diploid DNA content [43, 46]. carcinomatous transformation can be brought about by dys- regulation of the mechanisms controlling the cell cycle, DNA repair, and apoptosis, by activation of proto-oncogenes, by loss of chromosomal regions containing candidate tumour- 5. Field Precancerization and Oral Leukoplakia suppressor genes as a result of loss of heterozygosity (LoH), The existence of a field or fields of precancerization can and by alterations to genomic DNA and to mitochondrial explain why oral leukoplakia may manifest at single or at DNA [23–25, 34, 35]. While these molecular and cytogenetic multiple sites, synchronously and/or metachronously and markers may not be reliable predictors of carcinomatous may recur at the same site from which it was previously transformation [1, 34, 36–38], there is a good deal of apparently successfully excised [1] evidence that LoH at specific chromosomal arms, and aneuploidy, are indeed associated with increased frequency Additional cytogenetic alterations superimposed upon of carcinomatous transformation of oral leukoplakia [35, 39– transformed precancerous keratinocytes either within a 43]. However, irrespective of one or more cytogenetic or leukoplakia or within a clinically normal-looking zone of molecular changes to the keratinocytes of oral leukoplakia, an epithelial field of precancerization may drive the process progression to carcinoma may never occur [1]. of cancerization. This explains why sometimes an oral LoH at the chromosome arms 3p and 9p occur frequently leukoplakia on microscopical examination is found to have in keratinocytes of precancerous epithelial lesions of the already become squamous cell carcinoma, and sometimes upper aerodigestive tract. This pattern of LoH can be associ- squamous cell carcinoma arises apparently de novo either ated with carcinomatous transformation of these lesions [18, contiguous to or separated from existing leukoplakia. If a 35, 40, 44, 45]. In one study, precancerous epithelial lesions substantial portion of a field of precancerization arises from with keratinocytes having LoH limited to 3p and/or 9p a monoclone of cytogenetically transformed keratinocytes, had a 3.8-fold higher risk of carcinomatous transformation then any leukoplakias, or subsequently developing carcino- compared to precancerous lesions without LoH either at mas arising within that field either contiguously or separately 3p or at 9p, while those lesions with keratinocytes carrying from each other, will be cytogenetically very similar or LoH at 3p and/or 9p, together with additional losses at any identical. On the other hand, if a field of precancerization of the chromosomes 4q, 8p, 11q, and 17p had a 33-fold comprises a number of clones of cytogenetically dissimilarly increased risk of carcinomatous transformation, compared transformed keratinocytes, then leukoplakias or carcinomas to precancerous lesions with keratinocytes retaining these arising within this field (if multiple lesions should occur) will chromosomal arms, and also progressed to carcinoma more be cytogenetically dissimilar [1, 30]. rapidly, although unpredictably [35, 41]. The transformed keratinocytes in the precancerized field For unknown reasons, keratinocytes of dysplastic oral from which a leukoplakia had apparently been completely leukoplakias on the floor of the mouth, on the ventrolateral excised may give rise to “recurrence” of another leukoplakia surface of the tongue, and at the maxillary retromolar/soft from cytogenetically related subclones of transformed ker- palate region have LoH more frequently than do the ker- atinocytes adjacent to the surgical excision or from adjacent atinocytes of dysplastic leukoplakias affecting other regions cytogenetically unrelated clones [45]. of the oral mucosa. This may be one of the factors The time of progression of oral leukoplakias with putting leukoplakias at the three sites of the oral mucosa keratinocytes with molecular profiles associated with car- mentioned, at higher risk of carcinomatous transformation cinomatous transformation, to squamous cell carcinoma if than leukoplakias at other lower-risk sites [41]. it occurs, unpredictably and inexplicably varies from six Notwithstanding, the increased risk of carcinomatous months to eight years [35, 41]. However, it may sometimes transformation associated with LoH in precancerous epithe- take more than 30 years for oral leukoplakia to progress lial lesions, not all oral leukoplakias with keratinocytic to squamous cell carcinoma [47], and the average period LoH, will progress to carcinoma, and as some oral leuko- for carcinomatous transformation ranges from 5 to 8 years plakias without keratinocytic LoH will indeed progress to [47, 48]. Neither the rate of progression of oral leukoplakia carcinoma, LoH is certainly not an infallible predictor of to carcinoma nor the mechanisms bringing about the carcinomatous transformation [1]. regression of oral leukoplakia, can be explained in terms of It seems that the presence of DNA aneuploidy in the cytogenetic characteristics of the precancerous field. keratinocytes of oral leukoplakia may be a valuable molecular The mechanisms that bring about regression of oral marker of carcinomatous transformation of oral leukoplakia leukoplakia in which the keratinocytes harbour cytogenetic and an indicator of poor prognosis. The frequency of changes associated with early transformational events are carcinomatous transformation of dysplastic oral leukoplakia obscure. However, it is possible that a continuous accumula- is much greater for those leukoplakias with keratinocytes tion of cytogenetic alterations may give rise to a precancerous showing DNA aneuploidy than for those with keratinocytes clone of cells that is inferior rather than superior in its with normal (diploid) DNA content, and subjects with competitive growth and fitness resulting in its replacement oral carcinoma developing from dysplastic leukoplakia with by, rather than in its replacing, the normal neighbouring 4 International Journal of Dentistry keratinocytes [1]. Alternatively, or additionally, the accumu- [14] L. A. Loeb, “A mutator phenotype in cancer,” Cancer Research, lated cytogenetic alterations may result in failure of DNA vol. 61, no. 8, pp. 3230–3239, 2001. replication and cell viability leading to the extinction of the [15] L. A. Loeb, K. R. Loeb, and J. 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