The primary risk factor for cervical cancer is infection with high-risk genotypes of human papillomavirus (HPV). This study compared HPV DNA detection between cervical swabs (CX) and self-administered vaginal swabs (SV). Phase I participants were 199 women chosen from a study comparing the detection of Chlamydia trachomatis from various anogenital sites. Phase II participants were 135 women from either the Colposcopy or HIV Outpatient Clinic. HPV DNA testing was performed using polymerase chain reaction and Roche reverse line blot hybridization. In Phase I samples, more CX samples amplified and more HPV genotypes (P < 0.05) were detected in CX. Genotype 52 were seen more in the cervix, whereas genotype 82 (MM4) was detected solely in the vagina. The presence of high-risk HPV genotypes in the cervix was a predictor of an abnormal Papanicolaou (Pap) smear. In Phase II samples, CX samples amplified more, but similar rates of HPV genotypes were seen in SV and CX samples. Higher concordance rates of high-risk genotypes were seen in Phase II compared to Phase I samples. Phase II demonstrated the feasibility of utilizing SV sampling to reflect cervical status. If validated, a self-vaginal swab method to detect cervical HPV DNA status could be utilized to triage women with indeterminate Pap smears and be a useful method to collect epidemiological data from large populations.