High grade squamous intraepithelial lesion on high-risk HPV negative patients: Why we still need the Pap test

Background: Cervical cancer is caused by high-risk human papillomavirus (hrHPV). Though screening Pap test (PT) has reduced cancer mortality by detecting precursor lesions, there is now a move toward replacing screening PT with hrHPV testing. The aims of this study were to determine hrHPV negative rate in high grade squamous intraepithelial lesion (HSIL) PT in high-risk patients and correlate with histopathology; and to review the hrHPV negative HSIL PT. Method: LIS was searched (January 2015–June 2016) for HSIL PT results. Patient chart was reviewed for age, hrHPV co-testing result including genotyping (Aptima^®), and histopathology follow-up (f/u) which was compared between hrHPV-positive and hrHPV-negative groups. hrHPV-negative HSIL PT slides were re-evaluated for concordance with original interpretation. Student t test was used for data analysis. Results: There were 230 patients with HSIL PT who had hrHPV co-testing and 199/230 had histopathological f/u. Majority (210/230, 91.3%) were hrHPV positive, and 20 (8.7%) were hrHPV negative. HrHPV negative HSIL was significantly more common in older women (mean age 49.3 years) compared with hrHPV-positive HSIL (mean age 40.7 years) (P =.0015). The most frequently detected genotype was HPV16 (40%). F/u was CIN2/3 in 145/181 (80%) hrHPV-positive HSIL (includes nine squamous cell carcinoma) and 6/16 (37.5%) hrHPV-negative HSIL. Conclusion: Although the risk of CIN2/3 and carcinoma was higher in hrHPV-positive patients, possibility of hrHPV-negative dysplastic lesions should be considered in older women as 6 of 16 (37.5%) of these women had CIN2/3 and/or carcinoma which would have been missed without the PT.