P16 expression and recurrent cervical intraepithelial neoplasia after cryotherapy among women living with HIV

Daniel Maina, Michael H. Chung, Marleen Temmerman, Zahir Moloo, Jonathan Wawire, Sharon A. Greene, Elizabeth R. Unger, Nelly Mugo, Samah Sakr, Shahin Sayed, Christine J. McGrath

Research output: Contribution to journalArticlepeer-review


Background: The expression of p16 protein, a surrogate marker for high-risk human papillomavirus (hrHPV), is associated with cervical dysplasia. We evaluated correlates of p16 expression at treatment for high-grade cervical lesions and its utility in predicting the recurrence of cervical intraepithelial lesions grade 2 or higher (CIN2+) following cryotherapy among women with HIV. Methods: This is a subgroup analysis of women with HIV in Kenya with baseline cervical biopsy-confirmed CIN2+ who were randomized to receive cryotherapy and followed every six-months for two-years for biopsy-confirmed recurrence of CIN2+. P16 immunohistochemistry was performed on the baseline cervical biopsy with a positive result defined as strong abnormal nuclear expression in a continuous block segment of cells (at least 10–20 cells). Results: Among the 200 women with CIN2+ randomized to cryotherapy, 160 (80%) had a baseline cervical biopsy specimen available, of whom 94 (59%) were p16-positive. p16 expression at baseline was associated with presence of any one of 14 hrHPV genotypes [Odds Ratio (OR) = 3.2; 95% Confidence Interval (CI), 1.03–9.78], multiple lifetime sexual partners (OR = 1.6; 95% CI, 1.03–2.54) and detectable plasma HIV viral load (>1,000 copies/mL; OR = 1.43; 95% CI, 1.01–2.03). Longer antiretroviral therapy duration (≥2 years) at baseline had lower odds of p16 expression (OR = 0.46; 95% CI, 0.24–0.87) than <2 years of antiretroviral therapy. Fifty-one women had CIN2+ recurrence over 2-years, of whom 33 (65%) were p16-positive at baseline. p16 was not associated with CIN2+ recurrence (Hazard Ratio = 1.35; 95% CI, 0.76–2.40). Conclusion: In this population of women with HIV and CIN2+, 41% of lesions were p16 negative and baseline p16 expression did not predict recurrence of cervical neoplasia during two-year follow up.

Original languageEnglish
Article number1277480
JournalFrontiers in Medicine
Publication statusPublished - 2023


  • CIN2+
  • HIV
  • cervical cancer
  • cervical lesions
  • cryotherapy
  • p16
  • recurrence


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