The site of infection and ethnicity of the patient influence the biological pathways to HPV-induced mucosal cancer

Abstract

High-risk human papillomaviruses are the causative agents of cervical cancer and are also believed to be aetiologically involved in a subset of squamous cell carcinomas of the head and neck region, especially the tonsil. Cervical cancers arise through disruption of the pathways of p53 and the product of the retinoblastoma gene by the human papillomavirus oncoproteins E6 and E7. It is generally assumed that the same pathways are involved in human papillomavirus-induced carcinogenesis at other mucosal surfaces. However, the patterns of expression of cell cycle proteins targeted by human papillomavirus E6 and E7 in cancers from different anatomic sites have been inconsistent, due to either biologic or technological factors. In this study, 73 human papillomavirus, 16-positive cervical squamous cell carcinomas (35 from Australian and 38 from Chinese women) were analysed for the expression of p53, pRb, p16 INK4A , p21 CIP1/WAF1 , p27 KIP1 and cyclin D1 by semiquantitative immunohistochemistry. Cervical cancers from Chinese women were found to be significantly more likely to overexpress p53, pRb, p21 and p27 than their Australian counterparts. These findings were compared with those from 31 human papillomavirus 16-positive tonsillar squamous cell carcinomas, all of Australian origin, tested using the same methodology. Comparisons of the tonsillar and combined cervical data showed that tonsillar cancers were significantly more likely to be p53-positive, whereas cervical cancers were significantly more likely to overexpress pRb, p16 and p27. When the tonsillar data were compared with cervical data from Australian women, the associations for p53 and pRb remained. These findings represent new evidence that the molecular pathways to human papillomavirus-induced mucosal cancer may be influenced by anatomic location and ethnicity.

Molecular analyses and prognostic relevance of HPV in head and neck tumours

“…Some authors failed to reveal high HPV prevalence level in countries with a high incidence of HN cancers, demonstrating a scarce contribution of HPV in carcinogenesis (21,22) while others even reported the absence of HPV DNA in a Chinese population, though of small size (23). Reasons of these oscillations seem to be ascribed to population variability, ethnic factors and anatomic location as well as recognised exposures to risk factors such as smoking and alcohol, more than methodological differences (4,24). In the present study the HPV prevalence rate for all HN sites was 18.3%; this percentage is slightly lower than that recently reported by Kreimer et al (4), who estimated a worldwide mean value of 25.9% in the systematic review of studies conducted in a large number of countries.…”

Tongue and tonsil carcinoma

“…The mechanism for this is also believed to be mediated by HPV-E6 and HPV-E7 oncoproteins although recent expression analysis of p53 and other cell cycle proteins at this site suggests that the mechanism may differ from that occurring in the uterine cervix. 24 The possible association between HPV infection and oral cavity SCC has been explored by many investigators. However, these studies have yielded varying results.…”

“…Cervical carcinomas arise via HPV-E6 and HPV-E7-mediated disruption of p53 pathways and deregulation of the retinoblastoma gene. 24 HPV is also known to be involved in the development of a subset of mucosal carcinomas in the head and neck particularly those arising in the tonsil. The mechanism for this is also believed to be mediated by HPV-E6 and HPV-E7 oncoproteins although recent expression analysis of p53 and other cell cycle proteins at this site suggests that the mechanism may differ from that occurring in the uterine cervix.…”

p16 Expression in cutaneous squamous carcinomas with neck metastases: A potential pitfall in identifying unknown primaries of the head and neck

“…If these methods do not identify a primary tumor, pathologic assessment of lymph node specimens may provide further information. The presence of HPV favors an oropharyngeal primary and, thus, more targeted locoregional treatment …”