International J. of Healthcare and Biomedical Research, Volume: 2, Issue: 4, July 2014, Pages 58-62

Case Report: HPV induced Proliferative verrucous Leukoplakia : Case Report

Dr Gopal Sharma, Dr Deepa Das , Dr Prachi Naik , Dr Jaya Mukherjee Oral Medicine and Radiology Department, YMT Dental College and Hospital, Mumbai. India Corresponding author: Dr Jaya Mukherjee

Abstract: Proliferative verrucous leukoplakia (PVL) is a recently delineated entity that is defined as a diffuse, white and smooth or papillary or wart like area of the oral mucosa caused by varying degrees of epithelial hyperplasia. 1 The synonymous term is oral florid papillomatosis. Ismail mullah a 32yr old man reported to Ymt Dental College and Hospital with a chief complaint of a white growth protruding out of the mouth since 1 yr. Patient also reported of esthetic concern and reduced mouth opening due to the growth. The patient first noticed a small white growth 1 year back in the lower left region of the mouth. The patient ignored the growth since it was small and painless. PVL has different features in these populations. Treatment recommendation includes multiple techniques such as CO2 laser surgery, surgery with radiotherapy, cryotherapy, retinoid, systemic vitamin A, bleomycin and photodynamic therapy. 12 Whether PVL progresses especially rapidly in Asian or Indian populations requires further investigation. Thehealth of these patients, especially their immune status,warrants examination for its contribution to the aetiology of PVL.

Introduction : time, becomes exophytic and wart like, display Proliferative verrucous leukoplakia (PVL) is a verrucal projections and areas of erythematous recently delineated entity that is defined as a change within white patches, and have the diffuse, white and smooth or papillary or wart like appearance of verrucous and nodular leukoplakia. 2 area of the oral mucosa caused by varying degrees Ultimately, many progress to invasive cancer, and of epithelial hyperplasia.1 The synonymous term is 30% or more of patients with PVL die of this oral florid papillomatosis. In 1985, Hansen et al disease. 6 coined the term “proliferative verrucous Case Report: leukoplakia” (PVL). PVL is known for its aggres- Ismail mullah a 32yr old man reported to Ymt sive pathology, given its multifocal involvement, Dental College and Hospital with a chief complaint tendency to recur after removal, and high rate of of a white growth protruding out of the mouth since malignant transformation, which can be higher than 1 yr. Patient also reported of esthetic concern and 70%, reaching 100% in some cases. 2 Its malignant reduced mouth opening due to the growth. The transformation rate varies from 0.1% to patient first noticed a small white growth 1 year 17.5%.3,4,5 .PVL is of uncertain etiology but may be back in the lower left region of the mouth. The associated with human papillomavirus (HPV) patient ignored the growth since it was small and infection. They suggest that HPV-16 infection may painless. The growth rapidly increased in size play an important role in theses lesions, although thereafter. Hence patient consulted a local some have failed in patients with PVLG to detect physician for the same, six months back. The HPV-DNA by PCR. Lesions of PVL tend to be physician advised him to undergo a biopsy for the slow-growing, persistent and irreversible which in growth. The biopsy revealed it to be a benign HPV 58 www.ijhbr.com ISSN: 2319-7072

International J. of Healthcare and Biomedical Research, Volume: 2, Issue: 4, July 2014, Pages 58-62

induced lesion. Patient was then advised with a homeopathic medication which he continued for 3 months, after which there was initial reduction in the size of the growth. He discontinued the medicine 3 months back and the growth has increased rapidly since then to the present size. Past dental and family history were non contributory. General examination revealed that the patient was well oriented with time space and FIG 2- PROLIFERATIVE VERRUCOUS person. LESION

Intra orally, a whitish exophytic proliferative growth was seen in the left labio-buccal mucosa extending from the commissural area to mesial of 36 involving the occlusal line and crossing it in a linear fashion and extending superiorly in the area of maxillary premolar, to involve the attached gingiva and the labial surfaces of the maxillary teeth extending from distal of 23 to the mesial of 27. The surface of the growth was hyperkerototic,

FIG 1-PROFILE PHOTO exuberant and exophytic with multiple nodular projections with fissures in between. The periphery Extra-oral examination revealed that the face was of the growth had white keratotic areas The hyper symmetrical. No obvious swelling or deformity keratotic growth had rough surface giving a warty was seen. The lips were incompetent due to growth appearance with palpable multiple papillary on the lips and the mouth opening was reduced . projections of hyperkeratotic tissue giving leathery On palpation of the temporomandibular joint, there feel. The growth was friable, non scrapable and non was no clicking, deviation or tenderness present tender. .Lymph nodes were non palpable. Based on the above clinical findings, a provisional diagnosis of proliferative verrucous leukoplakia was given. There was no involvement of the bone in the radiograph. An incisional biopsy was done and the specimen was sent for histopathological and for HPV analyses.

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1-molecular weight marker, 2- negative control, FIG-3 INCISIONAL BIOPSY 3-HPV positive sample, 4- hpv positive control

PCR was done for HPV detection which revealed The histopathology of the specimen revealed presence of HPV DNA and the genotype revealed stratified squamous epithelium with hyperkeratosis, HPV 16 in the sample. Based on the above parakeratosis and acanthosis with verrucoid findings, a final diagnosis of HPV induced hyperplasia. Focal koilocytotic change and proliferative verrucous leukoplakia was given .The lymphoid infiltrate at the dermoepidermal junctions patient was advised wide excision of the growth was noted. Mild atypia of basal keratinocytes and with laser as a treatment modality and a follow up occasional keratotic pearl was seen. There was no after 6 months. unequivocal evidence of invasive malignancy. The DISCUSSION overall picture was suggestive of verrucoid lesion PVL is a progressive condition which develops with mild atypia consistent with HPV induced wart. initially as a white plaque of hyperkeratosis that

eventually becomes a multifocal disease with confluent, exophytic and proliferative features. This is in accordance with the findings in our case report. The lesions are slow-growing yet persistent, as well as irreversible and resistant to all forms of treatment with a high recurrence rate. 7PVL as described by Hansen develops through a histopathological continuum stages from - normal oral mucosa (0), homogeneous leukoplakia (2), verrucous hyperplasia (4), verrucous carcinoma (6), papillary squamous cell carcinoma (8), and poorly differentiated carcinoma (10), in which the odd scores refer to a status intermediate between those referred to a status intermediate encompassing 10 between those referred to by the adjacent even scores .2 Recently Bagan et al 2010 8 also proposed a

set of diagnostic criteria to allow for the early FIG 4- HISTOPATHOLOGY identification of PVL cases. The proposal includes 1 2 3 4 60 www.ijhbr.com ISSN: 2319 -7072 International J. of Healthcare and Biomedical Research, Volume: 2, Issue: 4, July 2014, Pages 58-62

five major criteria and four minor criteria as the expression in HPV and oral SCC. Flow cytometric following: analysis was given by Kahn MA13, Lowe et al. 10 Major criteria (MC): observed the positive association between 1) A leukoplakia lesion with more than two histopathological severity and nuclear morph- different oral sites, which is more frequently found ometrical alteration in cases of PVL. PVL being an in the clinical diagnosis, exact nature of the lesion can gingival and alveolar processes and palate. only be judged by its histopathological evaluation. 2) The existence of a verrucous area The disease reported here developed rapidly within 3) The lesions spread or become engrossed during one year of the patient’s initial clinic visit. development of the disease. Therefore, we speculate that when PVL progresses 4) Recurrence in a previously treated area. to moderate dysplasia or malignancy, it is supposed 5) Histopathologically, there can be simple to develop rapidly and not remain so chronic as its epithelial hyperkeratosis to verrucous hyperplasia, early stage. Furthermore, previous studies have verrucous carcinoma or oral squamous cell primarily focused on Caucasian subjects, reflecting carcinoma. the growth status and properties of PVL only Minor criteria (mc): among these ethnic groups, so there is little 1) An oral leukoplakia lesion that occupies at least knowledge of PVL in Asian or specifically Indian 3cm when adding all the affected areas. populations 11 . Therefore, it must be determined 2) The patient is female whether 3) The patient (male or female) is a nonsmoker PVL has different features in these populations. 4) A disease evolution more than 5 years. Treatment recommendation includes multiple Our case fulfilled all the major criterias and two techniques such as CO2 laser surgery, surgery with minor criterias. The most common locations are the radiotherapy, cryotherapy, retinoid, systemic gingiva or alveolar ridge (often extending into the vitamin A, bleomycin and photodynamic therap- vestibule), tongue, and buccal mucosa-sites that y. 12 Whether PVL progresses especially rapidly in traditionally have not been considered high-risk Asian or Indian populations requires further inves- areas for the development of oral squamous cell tigation. Thehealth of these patients, especially carcinoma, with the exception of the tongue. their immune status,warrants examination for its Immunohistochemical studies by Gopalakrishnan R contribution to the aetiology of PVL. et al. 9 found mutated and wild-type p53 over

REFERENCES : 1. Sapp JP, Eversole LR, Wysocki GP. Contemporary Oral and Maxillofacial Pathology, 2nd edition. St. Louis, MO Mosby 2004178-179. 2. Hansen LS, Olson JA, Silverman S Jr: Proliferative verrucous leukoplakia: A long-term study of thirty patients. Oral Surg Oral Med Oral Pathol 1985; 60:285. 3. Silverman S Jr, Gorsky M, Lozada F. Oral leukoplakia and malignant transformation. A follow-up study of 257 patients. Cancer. 1984;53:563-8. 4. Lind PO . Malignant transformation in oral leukoplakia. Scand J Dent Res. 1987;95:449-55.

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International J. of Healthcare and Biomedical Research, Volume: 2, Issue: 4, July 2014, Pages 58-62

5. Scheifele C, Reichart PA, Dietrich T. Low prevalence of oral leukoplakia in a representative sample of the US population. Oral Oncol. 2003;39:619-25 6. Palefsky JM, Silverman S Jr, Abdel-Salaam M, et al: Association between proliferative verrucous leukoplakia with human papilloma virus type 16. J Oral Pathol Med 1995; 24:193. 7. J Bagan, C Scully, Y Jimenez, M Martorell. Proliferative verrucous leukoplakia: a concise update. Oral Diseases (2010) 8. Bagan JV, Lapiedra RC , Martinez DB, López LM, Gómez GE.proliferative verrucous leukoplakia:A proposal for diagnostic criteria. Med Oral Pathol Oral Cir Buccal. 2010 Nov 1;15(6):e839-45. 9. Gopalakrishnan R, Weghorst CM, Lehman TA, et al. Mutated and wild-type p53 expression and HPV integration in proliferative leukoplakia and oral squamous cell carcinoma. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1997; 83:471 10. Lowe NP, Cordova SW, Betterman BL, Hodges JS and RohrerMD. 0312 Computerized nuclear morphometry of PVL. 11. Ghazali N, Bakri MM, Zain RB: Aggressive, multifocal oral verrucous leukoplakia: proliferative verrucous leukoplakia or not? J Oral Pathol Med 2003, 32:383-392. 12. Poveda-Roda R, Bagán JV, Jiménez-Soriano Y, et al. Retinoids and proliferative verrucous leukoplakia (PVL). A preliminary study. Med Oral Patol Oral Cir Bucal 2010;15:e3–9. ------Date of submission: 15 May 2014 Date of Publication: 17 July 2014 Source of support: Nil Conflict of interest: Nil ------

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