The high risk human papillomaviruses and oral cancer: evidence for and against a causal relationship

Abstract

Oncogenic human papillomaviruses (HPVs) have been detected in oral squamous cell carcinoma (SCC).HPV16 is the most frequently detected HPV type in oral SCC and is present in up to 22% of cases, either alone or in combination with other HPV typeS. HPV18 is present in up to 14% of caseS. HPV16 and HPV18 are present together in approximately 6% of caseS. However, HPV16 and 18 are also detected in normal oral mucosae (10% and 11% of subjects, respectively). These data suggest that high risk HPV infection may be a co‐factor in oral carcinogenesis and that latent HPV infection of the oral mucosa is common. A role for HPV infection in oral car‐cinogenesis is supported by the ability of high risk HPVs to immortalize oral keratinocytes in vitro. Immortalization may involve (i) deactivation of pre‐formed tumor‐suppressor proteins by viral oncoproteins, (ii) blocking of tumor‐suppressor gene transcription as a result of HPV oncogene insertion or (iii) stimulation of cellular oncog‐ene transcription by the upstream insertion of HPV‐derived transcription activating sequenceS. Hence, infection of oral keratinocytes with high risk HPV may be involved in the pathogenesis of some oral SCCs although the evidence implicating HPV in oral carcinogenesis is, at present, mainly circumstantial.

No high-risk HPV detected in SCC of the oral tongue in the absolute absence of tobacco and alcohol—a case study of seven patients

“…It is generally accepted that there is a strong association between tonsillar SCC and HR-HPV [5][6][7][8]. However, with regard to the oral cavity, no unambiguous conclusions can yet be drawn as to whether HR-HPV also plays a role in the development of oral SCC [2,5,9]. The International Agency for Research on Cancer multicentre study by Herrero et al [10] detected HR-HPV DNA in 3.9% of the biopsy specimens of the oral cavity, whereas a large population-based review study conducted by Kreimer et al [11] reported that the HR-HPV prevalence in SCC of the oral cavity was 23.5%.…”

An Overview of the Spindle Assembly Checkpoint Status in Oral Cancer

“…In Southeast Asia, oral cancer shows the highest incidence and prevalence due to influence of tobacco and betel quid chewing habits [11]. High-risk human papilloma viruses (HR-HPVs) and Epstein-Barr virus (EBV) have also been identified as increasingly important risk factors [12–16]. Within the spectrum of oral malignancies, almost 90 percent are squamous cell carcinomas (SCC) [17].…”

Immortalization of normal human gingival keratinocytes and cytological and cytogenetic characterization of the cells

“…Most studies with human oral keratinocytes on the mechanism of oral carcinogenesis are performed with cells immortalized by introduction of human papillomavirus (HPV) type 16 DNA, 15,16 which may come from the circumstantial evidence suggesting that high-risk HPVs, such as HPV-16 and HPV-18, are associated with oral carcinogenesis. 20 However, because various etiological factors are known for oral cancer, it is important to establish new human ke ratinocyte cell lines useful for studying the mechanism of neoplastic transformation, which is a multistage process including immortalization and malignant transformation, both of which are important steps in squamous carcinogenesis.…”