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This study aimed to identify risk factors for squamous intraepithelial lesions (SIL) in women with known HIV status and to explore the association between SIL, HPV subtype, and HIV-induced immunosuppression. The study population consisted of women with known HIV serological status who were attending a network of 16 clinical centres in Italy. Detailed behavioural data, clinical and laboratory parameters, and samples for diagnosis of SIL by Papanicolau smear and HPV infection using a polymerase chain reaction (PCR) were obtained from each study participant. The strength of the association between SIL and possible risk factors was assessed calculating crude and adjusted odds ratios derived from univariate analysis and multivariate models. We enrolled 236 women, of whom 135 (57.2%) were HIV-infected. SIL was diagnosed in 57 women (24.1%); of these, 48 (35.6%) were HIV-infected and 9 (8.9%) were HIV-negative. HPV-DNA was detected in 41 (72%) women with SIL and in 45 (25%) women without SIL. HPV-DNA was more often detected among HIV-infected women than among HIV-negative women (40% vs. 32%), but the difference was not statistically significant. Women infected with high-risk types or with low-risk-uncharacterised types of HPV both had a higher risk of SIL compared with HPV-negative women (respectively, AOR: 17.53 and AOR: 2.89). HIV-infected women with severe or moderate immunosuppression were more likely to have SIL than HIV-negative women (respectively, AOR: 7.29 and AOR: 3.09) also independently from HPV infection. Women reporting use of a contraceptive pill had a 2.5 times higher risk of SIL compared with those who never used hormonal contraceptives. The results confirm that high-risk HPV types are strongly associated with SIL, and that HIV infection may strengthen the effect of HPV at cervical level. The use of oral contraceptives may slightly increase the risk of SIL in women with at-risk behaviour for HIV infection.