title: 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.
authors.affiliation: Sydney Head and Neck Cancer Institute, Royal Prince Alfred Hospital, Sydney, Australia.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Carol H
authors.initials: CH
authors.lastname: Thompson
authors.forename: Yvonne E
authors.initials: YE
authors.lastname: Cossart
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: O'Brien
authors.forename: Jihong
authors.initials: J
authors.lastname: Liu
authors.forename: Richard A
authors.initials: RA
authors.lastname: Scolyer
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Carter
authors.forename: Christopher
authors.initials: C
authors.lastname: Dalrymple
authors.forename: Barbara R
authors.initials: BR
authors.lastname: Rose
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001315:Australia; D002294:Carcinoma, Squamous Cell / Q000208:ethnology / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D018797:Cell Cycle Proteins / Q000032:analysis; D002681:China; D019938:Cyclin D1 / Q000032:analysis; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000032:analysis; D050759:Cyclin-Dependent Kinase Inhibitor p21; D050760:Cyclin-Dependent Kinase Inhibitor p27; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009367:Neoplasm Staging; D027383:Papillomaviridae; D030361:Papillomavirus Infections / Q000150:complications*; D016160:Retinoblastoma Protein / Q000032:analysis; D014067:Tonsillar Neoplasms / Q000208:ethnology / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000032:analysis; D025521:Tumor Suppressor Proteins / Q000032:analysis; D002583:Uterine Cervical Neoplasms / Q000208:ethnology / Q000209:etiology / Q000378:metabolism / Q000473:pathology
chemical_list: C493956:CDKN1A protein, human; D018797:Cell Cycle Proteins; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D019938:Cyclin D1; D050760:Cyclin-Dependent Kinase Inhibitor p27