Environmental co-factors in HPV carcinogenesis.

Epidemiological studies have shown that only a small fraction of women infected with oncogenic HPV types will eventually progress to high-grade intraepithelial lesions (HSIL) and cervical cancer (CC). Because infection by oncogenic HPVs is a necessary but not a sufficient cause of CC, it has been assumed that other factors, acting in conjunction with HPV, influence the risk of transition from cervical HPV infection to cervical malignancy. This paper reviews the epidemiological evidence for the role of environmental co-factors in HPV carcinogenesis as assessed from selected studies that report associations within a well-defined HPV-DNA positive group. Co-factors assessed include parity, use of oral contraceptives, tobacco smoking, infection with other sexually transmitted diseases, and dietary and nutritional factors. Based on the evidence provided by the largest epidemiological studies that using sensitive detection methods allowed for the effects of HPV, it can be concluded that, among HPV positive women, high parity, long-term OC use, smoking, and co-infection with other sexually transmitted agents are the most consistently identified environmental co-factors likely to influence the risk of progression from cervical HPV infection to HSIL and invasive CC. There is limited evidence for a role of dietary factors in HPV carcinogenesis. On-going epidemiological studies will shed more light into the role of these and other co-factors, but if confirmed, these conclusions may imply that multiparous women, women who are smokers, and women on long-term OC use, might need a closer cytological and HPV surveillance than women in the general population.