“High Risk” HPV Types Are Frequently Detected in Potentially Malignant and Malignant Oral Lesions, But Not in Normal Oral Mucosa

Abstract

Studies on the involvement of the human papillomavirus (HPV) in initiation and progression of oral neoplasia have generated conflicting results. The observed discrepancy is attributable mainly to the varying sensitivity of the applied methodologies and to epidemiologic factors of the examined patient groups. To evaluate the role of HPV in oral carcinogenesis, we analyzed 53 potentially neoplastic and neoplastic oral lesions consisting of 29 cases of hyperplasia, 5 cases of dysplasia, and 19 cases of squamous cell carcinomas, as well as 16 oral specimens derived from healthy individuals. A highly sensitive nested polymerase chain reaction (PCR) assay was used, along with type-specific PCR, restriction fragment length polymorphism analysis, dot blotting, and nonisotopic in situ hybridization. Nested PCR revealed the presence of HPV DNA in 48 of the 53 (91%) pathologic samples analyzed, whereas none (0%) of the normal specimens was found to be infected. Positivity for HPV was independent of histology and the smoking habits of the analyzed group of patients. At least one "high risk" type, such as HPV 16, 18, and 33, was detected by type-specific PCR in 47 (98%) infected specimens, whereas only 1 (2%) squamous cell carcinoma was solely infected by a "low risk" type (HPV 6). HPV 16 was the prevailing viral type, being present in 71% of infected cases. Single HPV 16 and HPV 18 infections were confirmed by restriction fragment length polymorphism. HPV 58 was detected by dot blotting in three hyperplastic lesions. HPV positivity and genotyping were further confirmed, and the physical status of this virus was evaluated by nonisotopic in situ hybridization. Diffuse and punctate signals, indicative of the episomal and integrative pattern of HPV infection, were observed for low-and high-risk types, respectively. Our findings are suggestive of an early involvement of high-risk HPV types in oral carcinogenesis.

Expression of cell cycle markers and human papillomavirus infection in oral squamous cell carcinoma: Use of fuzzy neural networks

“…33 Thus, other agents, such as viruses, are being investigated. 34 In particular, with regard to viral involvement, it is still highly controversial whether HR HPV can be considered an etiologic or a malignant risk factor in oral carcinogenesis: 14 some research groups 14,35,36 have identified HR HPV antigens and viral DNA in potentially malignant and malignant oral lesions, and others have defined HR HPV as playing an important role in OSCC, especially in the absence of common oral habits. 37 Historically, evidence of the carcinogenic role of HR HPVs is based on 2 oncoproteins: HPV-E6, which promotes degradation of the p53 tumor-suppressor gene product, 38 and HPV-E7, which modifies pRb tumor-suppressor gene product function, leading to increased cell proliferation and contributing to carcinogenesis.…”

Preneoplasia and carcinogenesis of the oral cavity

“…An etiologic role for HPV has also been suggested for verrucous carcinoma [13] and squamous cell carcinoma, including some of its variants [14,15]. The benign oral lesions are statistically associated with HPV types 2, 4, 6, 11, 13, and 32, and the malignant ones with HPV types 16, 18, and 33 [11,16]. Among the carcinomas, those with the highest incidence of HPV detection are the poorly differentiated non-keratinizing tumors of the tonsil seen in young individuals [17,18].…”

Prevalência do papilomavírus humano (HPV) na cavidade oral e na orofaringe

“…HPV 16 presence in oral cancer in many studies depicted in Table 4 does not prove that the virus be indeed responsible for the disease, notwithstanding, it does prove that it may contribute to the incidence of oral cancer, specially among non-smokers and non-alcoholics 3,45 , or even in the simultaneous presence of chemical agents and HPV infection, which may lead to malignant transformation.…”

“…Their genome is made up of 7,200 -8,000 base pairs with molecular weights of 5.2 x 106 Daltons. They have a capsule with 72 capsomeres of icosahedral structures, without lipoprotein envelope, and in a single circular double DNA molecule [2][3][4][5] .…”