Interactions between human papillomavirus and other sexually transmitted agents in the etiology of cervical cancer

The interplay between human papillomavirus, notably type 16, and HIV in cervical carcinogenesis leads to persistent infection and cervical neoplasia by destruction of the afferent arm (Langerhans cells) of the host immune system. The joint effect takes place at the early stages of squamous intraepithelial lesions and has severe consequences if left untreated. The recent increase of cervical cancer mortality in young women in developed countries may well be a result of the HIV epidemic. Infection with Chlamydia trachomatis is associated with cervical squamous cell carcinoma but not with cervical adenocarcinoma, and the association remains after adjusting for human papillomavirus 16. Joint effects of C. trachomatis and the human papillomaviruses have not been studied at the population level but indirect evidence from epidemiological studies suggests that the interaction might be different (synergistic versus antagonistic) at different stages (cervical intraepithelial neoplasia versus invasive cervical cancer) of cervical carcino-genesis. Concomitant exposure to human papillomaviruses 6 or 11 and human papillomavirus type 16 has not been shown to result in excess risk of cervical squamous cell carcinoma. This antagonistic joint effect was also discovered between human papillomavirus types 18 and 16, as well as 33 and 16. Herpes simplex virus type 2 antibodies are associated with a modest risk of cervical cancer, which is not surprising since the presence of herpes simplex virus antibodies reflects risk-taking sexual behaviour. However, no excess risk remains after adjustment for human papillomavirus type 16, and no interaction between these two viruses has been found in epidemiological studies. Evidence of interaction between human papillomavirus type 16 and the other members of the herpesvirus family is still at an experimental level and difficult to judge. Little progress has been made in the most promising experimental association between the oncogenic human papillomaviruses and adeno-associated viruses. In addition to the well established interaction between human papillomaviruses and HIV, intriguing interactions are emerging between the human papillomaviruses and C. trachomatis, as well as between the different human papillomavirus types.