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.
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