JOURNAL OF CRITICAL REVIEWS ISSN- 2394-5125 VOL 7, ISSUE 14, 2020 HPV- RELATED ORAL LESIONS- A REVIEW Nishanth.G 1, Aravindha Babu.N 2, N.Anitha3, L.Malathi3 1Post Graduate student, Sree Balaji Dental College and Hospital , Bharath Institute of Higher Education ( BIHER) Chennai 2Professor, Sree Balaji Dental College and Hospital , Bharath Institute of Higher Education ( BIHER) Chennai 3Reader, Sree Balaji Dental College and Hospital , Bharath Institute of Higher Education ( BIHER) Chennai Received: 14 March 2020 Revised and Accepted: 8 July 2020 ABSTRACT: Human papillomavirus (HPV) includes the majority of newly acquired sexually transmitted infections (STIs). Genital HPV is the most common STI with incidence of about 5.5 million world‑wide, nearly 75% of sexually active men and women have been exposed to HPV at some point in their lives. Oral Sexual behavior is an important and contributing factor to infection of HPV in the oral mucosa especially in cases known to practice high risk behavior and initiating the same at an early age. HPV infection of the oral mucosa in the current concept is believed to affect 1‑50% of the general population, depending on the methods which are used for diagnosis. The immune system clears most HPV naturally within 2 years (about 90%), but the ones that persist can cause serious diseases. HPV is an essential carcinogen being implicated increasingly in association with cancers occurring at numerous sites in the body. Though there does not occur any specific treatment for the HPV infection, the diseases it causes are treatable such as genital warts, cervical and other cancers. In addition, recent data clearly suggest that more than one HPV type is involved in the development of the squamous cell lesions in the oral cavity KEY WORDS: Human papillomaviruses; Oral infection; Prevention; Transmission I. INTRODUCTION: Human papilloma virus (HPV) is the most common sexually transmitted infections. It is assumed that two thirds of people who have unprotected sexual intercourse are infected [1]. Since HPV has affinity for epithelial tissue [2-4], it can infect both skin and mucosa [3,4]. For several types of injuries, ranging from asymptomatic infection and benign warts to invasive injuries HPV are responsible [5]. The anatomical sites of HPV infections are : genital and anal tract, urethra, upper airway, tracheobronchial mucosa, nasal paranasal cavities, and oral cavity. 1% to 43% of the general population, are affected depending on the diagnosis method used and may be even associated with oral malignancies [6]. VIRION STRUCTURE: HPV is a DNA virus belonging to Papillomaviridae family [1,2,7,8]. It consists of a non enveloped, singular double stranded DNA molecule [5,8,9], involved by a capsid, of about 55 nm in diameter [8, 9], containing only two structural proteins[8]. It weighs 5.2x106D and contains 7.200 – 8.000 pairs of nitrogenous bases (pnb) [9]. Non- coding strand probably forms a second, which bears pieces of preserved ORFs, irrespective of localization and composition [8]. Chlaudhary et al have suggested that the basis of the HPV molecule DNA can be divided in three parts. The first part, helps for viral replication and cell transformation while the second part, is an important zone, since it encodes the viral particle structural proteins. The last one contains a non-coding zone and the viral origin of replication belongs to this part[9]. GENOME STRUCTURE: The difference of HPV types is due to the difference of E6 and E7 sequence of nitrogenous bases. This variation can produce both easier to inhibit gene or a harder to inhibit one, thus divided the virus oncogenic phenotype into high, intermediate and low risk types [7].Besides its oncogenic potential, the HPV types vary according to their association with these tissues and tropism [10]. Low-risk HPV[11] causes injuries which produce abnormal cell growth [8]; however, they are unlikely to undergo malignant neoplastic transformation. High-risk HPV[11] are likely to induce malignant neoplastic transformation [3, 11]. HPV - 6, 11 are related to condyloma acuminatum and, in children, laryngeal papilloma, conjuntival papilloma and genital warts [13]. 3562 JOURNAL OF CRITICAL REVIEWS ISSN- 2394-5125 VOL 7, ISSUE 14, 2020 PREVALENCE AND INCIDENCE: The American Cancer Society surveyed more than 6 million people are infected by HPV per year, with 3 million affecting the 15- 25 age group [14]. Oral and oropharynx HPV prevalence has not yet been established [15], probably because different methods were used in different studies [3]. Methods varies in terms of size of samples, collecting procedures, test sensibility and use of PCR or PCR Trends in Infectious Diseases18 inhibitors. This may be the cause for huge variation in HPV detection rate: 22 to 60% or 0 to 81.1%,[15]. ORAL HUMAN PAPILLOMAVIRUS INFECTION: When oral mucosa is regarded normal, the epithelium may additionally serve as a container of HPV which would be activated at some point in time and set off harm [16]. A big quantity of extraordinary oral ailments may also be associated with oral HPV, but they hardly ever cause lesions [17]. Lesions may vary from benign warts, which are a long way more common, to malignant injuries [6]. SEXUAL AND NONSEXUAL TRANSMISSION: Many research have mentioned HPV transmission, however the mechanisms concerned stay unknown. Unprotected sexual intercourse is its main cause, mainly oral-genital sex, when the genital mucosa is contaminated by means of the virus, which will be present each clinically and subclinically [1, 16] in adolescent and adults. Early sexual relationships, high range of sexual partners, parity, smoking and another sexually transmitted contamination may additionally raise the charge of virus infection[6,8,19]. Oral HPV can be transmitted by way of direct skin-skin contact [3] and self-inoculation [1,4]. Upper airway transmission has not been set up [8]. Infant HPV is more often than not transmitted at beginning by means of contamination of the maternal cervix. Thus, the recurrent laryngeal papillomatosis appears to be acquired by such manner[19,20]. However, every other transmission route is mother-fetus, before, all through or after the child-birth [1,4,8] that might also be made feasible by way of contaminated amniotic fluid and umbilical cord blood [21]. The transmission of HPV via fomites might also additionally occur[22]. II. HPV ASSOCIATED ORAL INJURIES: Condyloma acuminatum: The lesion is caused by the proliferation of a squamous stratified epithelium [23]. Formerly it was believed that the only transmission route was by sexual contact, but now it is known that there are other routes, such as self- inoculation and mother-fetus transmission [15]. However, sexual contact remains the main route of transmission (20%) [23], and people who carry these lesions and practice oral sex have a 50% chance to acquiring oral condyloma. The incubation period range from 3 weeks to an undetermined period of time; after that, clinic progression will depend on cell permissiveness, virus type and host immune situation [24]. Condyloma acuminatum has tropism to tongue, lips, palate and mouth floor. Clinically, it is described as little pinkish or whitish nodules which proliferate in papillary projections that might be either pedicle or sessile. Outline surfaces present even more evident cauliflower shapes than papilloma, mainly when they converge. HPV presence was first determined by immunohistochemistry and later by hybridization with 75 to 85% of positivity [15]. The most involved types are 6 and 11 [5,15,18,25]. Verruca vulgaris: Verruca vulgaris, is one of the common lesions affecting children[15], but not in oral mucosa[6]. It is found on lips, hard palate, gingival, and tongue dorsal surface[15], but specifically on lips and tongue[18]. Koilocytes may be seen in the connective tissue and some dilated capillaries and a mild infiltration with lymphocytes are usually noticed[26]. Immunohistochemical methods and hybridization tests showed HPV presence in 43 to 100% of the lesions[15]. Oral squamous papilloma: Oral squamous papilloma is a benign tumor occur in all age group but it more commonly affects adults from 30 and 50 years old[15]. It is mainly related to HPV 6 and 11[15,18]. The lesion is normally located in the oral mucosa, palate and tongue, laryngotracheobronchial complex is a more common site in children[27]. It affects the soft palate, the lingual frenulum as well as the lower lip [15] and the uvula [27], most often presenting as single, small lesion less than 1 cm, with exophytic growth and a wide basis and pedicle. Multiple-recurring papilloma is also more likely to be malignant[27] and tends to relapse more often [28]. 3563 JOURNAL OF CRITICAL REVIEWS ISSN- 2394-5125 VOL 7, ISSUE 14, 2020 Focal epithelial hyperplasia: Hecks disease was first described in 1965[15] and can affect all age groups[29], but it is more common in children and adolescents (3 to 18 years)[30]. Malnutrition, poor hygiene and low social condition and genetic background also play an important role[31] in lesion development. It shows a benign epithelial growth and commonly affects oral mucosa, lips, tongue[18], particularly the lower lip and more rarely the palate, floor of the mouth and oropharynx[30]. It presents as multiple papules (3 – 10 mm)[30] that tend to converge. Clinically nodular, sessile, circumscribed, painless and soft masses on oral mucosa. Color may range from pale pink to normal mucosa [15,29-31]. The diagnosis based on both clinical and histological[30,32]. It has a steady association with HPV infection, and the most common types are 13 and 32 [15,29]; they account for approximately 90% of infections[30,32]. Oral squamous cell carcinoma: In 1976, the main portrayal of connection among OSCC and HPV was depicted by Zur Hausen, from that point forward it has been as a select reason for Cervical Carcinoma[41] HPV was found in relationship to 20% of OSCC cases as detailed in 1983 by Syrjanen [33] .HNSCC are a significant reason for dismalness and mortality world‑wide particularly in the Indian subcontinent with > 90% of which are SCC and rank 6th among all malignancies worldwide[34].