Human papillomavirus and cancer

Abstract

The epidemiological evidence linking sexually transmitted HPV to cervical cancer is conclusive. Almost 100% of cervical cancers can be attributed to certain HPV types. HPV 16 accounts for the highest proportion (54%) followed by HPV 18 (14%), HPV 45 (9%) and HPV 31 (6%), with several other types accounting for the remaining cases. The aetiological role of HPV is clear for both squamous cell carcinomas and adenocarcinomas, but in the latter histological group HPV 18 is detected more frequently than other types. The association of HPV with cervical cancer is very strong and consistent, with ORs over 50 in recent case-control studies. The association is very strong not only for HPV 16 and 18 but also for less common HPV types. In addition, there is prospective evidence that infection precedes disease and extensive laboratory data indicating the carcinogenic potential of HPV. However, the high frequency of HPV infection in the cervix of young women indicates that HPV is a necessary but not sufficient cause and that co- factors must be present for only a small proportion of persistent infections eventually to progress to cancer. Potential co-factors under investigation include viral factors such as specific HPV types, viral load, molecular variants of HPV or expression of specific viral genes; host factors such as genetic polymorphisms of tumour suppressor genes, certain human leucocyte antigen alleles or haplotypes and specific immunological responses (including those associated with immunosuppressive therapy and HIV infection); hormonal influences such as those related to multiparity or the use of hormonal contraceptives; infections with other sexually transmitted agents such as Chlamydia trachomatis, HSV2 or non-specific vaginal infections; and probably smoking and certain dietary habits. The recognition of the central role of HPV in cervical cancer has far reaching implications for the primary and secondary prevention of this malignancy. An important fraction of other anogenital malignancies is also strongly associated with HPV and there is some evidence for a possible involvement of the virus in other epithelial cancers (eg head and neck, skin), but more research is needed to clarify the role of these viruses in other cancer sites.