HPV-related neoplasias in HIV-infected individuals A. Del Mistro *, L. Chieco Bianchi Department of Oncology and Surgical Sciences, Oncology Section, University of Padova, and Servizio Citologia Diagnostica Molecolare Oncologica, Azienda Ospedaliera di Padova, via Gattamelata, 64, 35128 Padova, Italy Received 5 February 2001; accepted 8 March 2001 Abstract Human papillomavirus (HPV) infection of the lower genital tract is now considered the most important factor in the initiation of neoplasia. Human immunodeficiency virus (HIV) infection appears to alter the natural history of HPV-associated oncogenesis, but its impact on gynaecology has only recently been defined; the Centers for Disease Control (CDC) designated moderate and severe cervical dysplasia as a category B defining condition, and invasive cervical cancer as a category C defining condition of AIDS in 1993. Anal HPV infection and anal squamous intra-epithelial lesions have been found to be highly prevalent among HIV-positive homosexual men, and recent preliminary data suggest a relatively high prevalence among HIV-positive women as well. Moreover, HPV infection and associated lesions are also observed in body sites other than the anogenital area, particularly the skin and the oral cavity. # 2001 Elsevier Science Ltd. All rights reserved. Keywords: Human papillomavirus; Squamous intra-epithelial lesions; Cervix; Vagina; Vulva; Anus; Penis; Skin; Immunodeficiency 1. Introduction Human papillomaviruses (HPVs) are small DNA viruses that cause benign and malignant epithelial pro- liferations. Because HPVs complete their life cycle only in fully differentiated epithelial cells, they are difficult to propagate in cell culture and, as a consequence, unlike most other viruses, their taxonomy is based on DNA homology rather than antigenic diversity. To date, 84 different genotypes have been fully cloned and sequenced, and the existence of at least 70 additional genotypes is suggested by polymerase chain reaction (PCR) analysis with degenerate consensus primers and subsequent sequencing [1]. HPVs are strictly epitheliotropic and tissue-specific, with cutaneous and mucosal types forming two distinct groups. Approximately 30–40 types infect the anogeni- tal area; this group includes the most extensively studied HPVs, and is associated with a large spectrum of dis- eases, from benign proliferations to invasive cancers (Table 1). It is now firmly established that HPVs play a central role in the pathogenesis of cervical cancer. Indeed, viral sequences are found in more than 99% of cervical can- cers worldwide, with type 16 present in 50%, and types 18, 31 and 45 in another 30% [2,3]. High grade cervical intra-epithelial neoplasia precursor lesions (CIN 2 and 3) have similarly high rates of the same HPV types [4,5]. Laboratory studies have demonstrated that cancer- associated types contain genomic sequences with onco- genic activity, E6 and E7, which are consistently retained and expressed in cancers, and able to interact with cell cycle regulators [6]. Based on the strength of their association with cervical cancer, genital HPVs fall into different risk categories, as follows: high risk: types 16, 18, 31 and 45 (each found in at least 5% of invasive cancers); intermediate risk: types 33, 35, 39, 51, 52, 56, 58, 59 and 68 (each found in 1–5% of invasive cancers); low risk: types 6, 11, 42, 43 and 44 and many others (rarely found in invasive cancers). The International Agency for Research on Cancer (France) and the National Institutes of Health (USA), both concluded that high risk and most intermediate risk genital HPV types act as carcinogens in the development of cervical cancer [4,7]. While the data supporting the role of HPV in other anogenital cancers are more limited, a large proportion 0959-8049/01/$ - see front matter # 2001 Elsevier Science Ltd. All rights reserved. PII: S0959-8049(01)00107-1 European Journal of Cancer 37 (2001) 1227–1235 www.ejconline.com * Corresponding author. Tel.: +39-49-821-5872; fax: +39-49-807- 2854. E-mail address: delmistr@ux1.unipd.it (A. Del Mistro).