Background The Cepheid Xpert® HPV Test has high sensitivity and specificity for the detection of HPV infection in women compared to the Roche cobas 4800 HPV assay using cervical specimens. In many high-burden, low-resource countries it will not be feasible to achieve high cervical screening coverage using HPV-DNA technologies that require clinician-collected samples. We are conducting the first evaluation of self-collected vaginal specimens compared to clinician-collected cervical specimens for the detection of HPV infection using the Xpert® HPV Test. This study is being conducted in Papua New Guinea, which has among the highest rates of cervical cancer globally, with an age-standardised incidence of 23.7/100,000 compared to 5.0/100,000 in Australia and New Zealand. Methods Women aged 30–54 years attending two Well Woman Clinics are invited to participate and following informed consent procedures, complete a short interview, clinical examination, and provide self-collected and clinician-collected cytobrush specimens for clinic-based HPV testing. Women are given their cervical test result the same day. Those with a positive HPV test and a positive examination on visual inspection of the cervix with acetic acid are offered same-day cervical cryotherapy. Results A total of 313 women were recruited to end-Feb 2015. There was 94.2% overall percentage agreement (OPA) between vaginal and cervical tests for all high-risk HPV (hrHPV) types; 100% OPA for HPV-16; and 99.7% OPA for HPV 18/45. Based on cervical test results, the prevalence of HPV-16 was 4.2% (13/313); HPV 18/45 was 1.6% (5/313); and other hrHPV, 11.8% (37/313). Overall, 15.7% (49/313) of participants had one or more hrHPV infection. Conclusion Preliminary results suggest that self-collected vaginal specimens compare favourably to clinician-collected cervical specimens for the detection of HPV infection using the Xpert® HPV Test. If confirmed, this finding is likely to have significant implications for future HPV-based cervical screening programs in high-burden, low-resource settings worldwide. Disclosure of interest statement Nothing to Disclose.