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

BackgroundThe 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 intraepitheli...

Full description

Bibliographic Details
Main Authors: 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
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-10-01
Series:Frontiers in Medicine
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fmed.2023.1277480/full
_version_ 1797662938318766080
author 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
author_facet 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
author_sort Daniel Maina
collection DOAJ
description BackgroundThe 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.MethodsThis 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).ResultsAmong 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).ConclusionIn 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.
first_indexed 2024-03-11T19:07:20Z
format Article
id doaj.art-891b67da8e8f43cba2cb187b9bb92b96
institution Directory Open Access Journal
issn 2296-858X
language English
last_indexed 2024-03-11T19:07:20Z
publishDate 2023-10-01
publisher Frontiers Media S.A.
record_format Article
series Frontiers in Medicine
spelling doaj.art-891b67da8e8f43cba2cb187b9bb92b962023-10-10T06:25:19ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2023-10-011010.3389/fmed.2023.12774801277480P16 expression and recurrent cervical intraepithelial neoplasia after cryotherapy among women living with HIVDaniel Maina0Michael H. Chung1Marleen Temmerman2Zahir Moloo3Jonathan Wawire4Sharon A. Greene5Elizabeth R. Unger6Nelly Mugo7Samah Sakr8Shahin Sayed9Christine J. McGrath10Department of Pathology and Laboratory Medicine, Aga Khan University Hospital, Nairobi, KenyaDivision of Infectious Diseases, Department of Medicine Emory University, Atlanta, GA, United StatesDepartment of Pathology and Laboratory Medicine, Aga Khan University Hospital, Nairobi, KenyaDepartment of Pathology and Laboratory Medicine, Aga Khan University Hospital, Nairobi, KenyaDepartment of Pathology and Laboratory Medicine, Aga Khan University Hospital, Nairobi, KenyaDepartment of Global Health, University of Washington, Seattle, WA, United StatesCenters for Disease Control and Prevention, Atlanta, GA, United StatesSexual Reproductive and Adolescent Child Health Research Program, Kenya Medical Research Institute, Nairobi, KenyaCoptic Hospital, Nairobi, KenyaDepartment of Pathology and Laboratory Medicine, Aga Khan University Hospital, Nairobi, KenyaDepartment of Global Health, University of Washington, Seattle, WA, United StatesBackgroundThe 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.MethodsThis 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).ResultsAmong 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).ConclusionIn 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.https://www.frontiersin.org/articles/10.3389/fmed.2023.1277480/fullCIN2+p16recurrencecryotherapyHIVcervical cancer
spellingShingle 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
P16 expression and recurrent cervical intraepithelial neoplasia after cryotherapy among women living with HIV
Frontiers in Medicine
CIN2+
p16
recurrence
cryotherapy
HIV
cervical cancer
title P16 expression and recurrent cervical intraepithelial neoplasia after cryotherapy among women living with HIV
title_full P16 expression and recurrent cervical intraepithelial neoplasia after cryotherapy among women living with HIV
title_fullStr P16 expression and recurrent cervical intraepithelial neoplasia after cryotherapy among women living with HIV
title_full_unstemmed P16 expression and recurrent cervical intraepithelial neoplasia after cryotherapy among women living with HIV
title_short P16 expression and recurrent cervical intraepithelial neoplasia after cryotherapy among women living with HIV
title_sort p16 expression and recurrent cervical intraepithelial neoplasia after cryotherapy among women living with hiv
topic CIN2+
p16
recurrence
cryotherapy
HIV
cervical cancer
url https://www.frontiersin.org/articles/10.3389/fmed.2023.1277480/full
work_keys_str_mv AT danielmaina p16expressionandrecurrentcervicalintraepithelialneoplasiaaftercryotherapyamongwomenlivingwithhiv
AT michaelhchung p16expressionandrecurrentcervicalintraepithelialneoplasiaaftercryotherapyamongwomenlivingwithhiv
AT marleentemmerman p16expressionandrecurrentcervicalintraepithelialneoplasiaaftercryotherapyamongwomenlivingwithhiv
AT zahirmoloo p16expressionandrecurrentcervicalintraepithelialneoplasiaaftercryotherapyamongwomenlivingwithhiv
AT jonathanwawire p16expressionandrecurrentcervicalintraepithelialneoplasiaaftercryotherapyamongwomenlivingwithhiv
AT sharonagreene p16expressionandrecurrentcervicalintraepithelialneoplasiaaftercryotherapyamongwomenlivingwithhiv
AT elizabethrunger p16expressionandrecurrentcervicalintraepithelialneoplasiaaftercryotherapyamongwomenlivingwithhiv
AT nellymugo p16expressionandrecurrentcervicalintraepithelialneoplasiaaftercryotherapyamongwomenlivingwithhiv
AT samahsakr p16expressionandrecurrentcervicalintraepithelialneoplasiaaftercryotherapyamongwomenlivingwithhiv
AT shahinsayed p16expressionandrecurrentcervicalintraepithelialneoplasiaaftercryotherapyamongwomenlivingwithhiv
AT christinejmcgrath p16expressionandrecurrentcervicalintraepithelialneoplasiaaftercryotherapyamongwomenlivingwithhiv