Repeated Positive Cervical HPV Testing and Absent or Minor Cytology Abnormality at Pap Smear. What is the Next Step

Background: Human papillomavirus (HPV) screening has significantly reduced cervical cancer (CC) mortality. Women who consecutively test positive for high-risk HPV without and minor changes on reflex cytology (atypical squamous cells of undetermined significance [ASC-US] or low-grade squamous intraepithelial lesion [LSIL]) or dysplasia on cervical colposcopy-oriented biopsy are always referred to colposcopy. The aim of the present study was to assess whether this guidance is appropriate for COBAS HPV testing with reflex cytology. Methods: A cross-sectional, retrospective study was carried out in 5,227 women who underwent routine CC screening over a period of five years (2012-2017). All HPV tests were performed using Cobas®4800 HPV. The study included women attending gynecology appointments whose first HPV test was positive and who had any type of follow-up. Patients’ HPV test results as well as cytology and biopsy findings obtained during the abovementioned period were analyzed. A descriptive and comparative statistical study was conducted using this data. Results: A total of 765 out of 6003 HPV tests performed in 5,227 women were positive, and 141 women who had a positive HPV test (with negative for intraepithelial lesion or malignancy [NILM] or inflammation, or ASC-US and LSIL cytology, but no lesions on colposcopy, or absence of dysplasia on histology) repeated the HPV test at least once. Of these 141 women, 6 were diagnosed with high-grade squamous intraepithelial lesion (HSIL) during the follow-up period. All cases of HSIL were diagnosed after the second HPV test. Conclusion: This study shows that, at cervical cancer screening, all women testing positive for HPV regardless of Pap smear result should be referred to colposcopy.