Objectives: To identify factors associated with high-risk human papillomavirus (HPV) infection and high grade squamous intraepithelial lesion (HSIL) among a high-risk group of HPV-unvaccinated women in Montevideo. Methods: Participants completed a questionnaire on socio-demographics, sexual behavior and gynecological history and received a gynecological examination. HPV DNA was detected by PCR using MY09/11 primers. Logistic regression analyses were performed to identify factors associated with high-risk HPV infection and HSIL. Results: A total of 469 women with HPV DNA and cytological results completed the questionnaire. Among women older than 30 years, those with high number of sexual partners and regular housing conditions were more likely to be positive for high-risk HPV infection (adjusted OR: 2.94, 95% CI: 1.01-8.51 and 2.68, 95% CI: 1.01-7.21, respectively). A marginally non-statistically significant association between getting a HSIL and having a high number of sexual partners was also observed (adjusted OR: 3.22, 95% CI: 0.97-10.75). Conclusions: In an era of development of new strategies for accelerating the reduction of cervical cancer incidence and mortality, our results may contribute to identify populations most susceptible to get benefit from broadening the scope for prevention of cervical cancer and could be used with other triage strategies