Human Papillomavirus Infections among HIV-Infected Subjects

Human papillomavirus (HPV) is the most common sexually transmitted infection and is the cause of anogenital warts (mostly HPV6,11) and cervical cancer (HPV16,18). Recently, other modes of HPV transmission have been established. The first evidence suggesting HPV involvement in the development of both benign and malignant squamous cell tumours of the larynx, mouth and oesophagus dates back to our original observations reported in 1977-1982. As in genital region, HPV has been detected in healthy mucosa, papillomas, pre-malignant lesions and cancers of the aero-digestive tract. Unlike in the genital tract, natural history of HPV in upper aero-digestive tract is poorly understood. Clinically detectable benign oral HPV lesions include papilloma, condyloma, wart and focal epithelial hyperplasia (FEH). FEH is familiar and has been associated with HPV types 13 and 32. It was recently shown that subjects with HLA-DRB1*0404 allele are at risk for FEH. Recent meta-analyses and several case-control studies have confirmed HPV as an independent risk factor for oral cancer (OR 3.7-5.4). Presence of HPV in oral cancer constitutes a prognostic marker of the disease. HPV16 is the single most frequent genotype.

Most data on HPV interactions with HIV are from the studies on genital lesions. Both HIV-infected women and men are at increased risk for genital and anal HPV in general, for infections with high-risk HPV types, persistent HPV infection, and developing intraepithelial neoplasms. In HIV-patients, also oral warts with multiple HPV types are more frequent. In the recent past, occurrence of many HIV-associated diseases has dramatically declined, except HPV-associated lesions. Thus, immune response is not a major determinant, and direct interaction between HIV and HPV may be involved in HPV-associated pathogenesis. The development of warts may be related to immune reconstitution as well. HIV might also play a role in HPV-associated pathogenesis by exerting oncogenic stimulus via Tat protein.