Abstract
Background: Primary human papillomavirus (HPV) screening (PHS) utilizes oncogenic human papillomavirus (oncHPV) testing as the initial cervical cancer screening method and typically, if positive, additional reflex-triage (eg, HPV16/18-genotyping, Pap testing). While US guidelines support PHS usage in the general population, PHS has been little studied in women living with HIV (WLWH). Methods: We enrolled n = 865 WLWH (323 from the Women's Interagency HIV Study [WIHS] and 542 from WIHS-affiliated colposcopy clinics). All participants underwent Pap and oncHPV testing, including HPV16/18-genotyping. WIHS WLWH who tested oncHPV[+] or had cytologic atypical squamous cells of undetermined significance or worse (ASC-US+) underwent colposcopy, as did a random 21% of WLWH who were oncHPV[-]/Pap[-] (controls). Most participants additionally underwent p16/Ki-67 immunocytochemistry. Results: Mean age was 46 years, median CD4 was 592 cells/μL, 95% used antiretroviral therapy. Seventy WLWH had histologically-determined cervical intraepithelial neoplasia grade 2 or greater (CIN-2+), of which 33 were defined as precancer (ie, [i] CIN-3+ or [ii] CIN-2 if concurrent with cytologic high grade squamous intraepithelial lesions [HSILs]). PHS had 87% sensitivity (Se) for precancer, 9% positive predictive value (PPV), and a 35% colposcopy referral rate (Colpo). "PHS with reflex HPV16/18-genotyping and Pap testing"had 84% Se, 16% PPV, 30% Colpo. PHS with only HPV16/18-genotyping had 24% Colpo. "Concurrent oncHPV and Pap Testing"(Co-Testing) had 91% Se, 12% PPV, 40% Colpo. p16/Ki-67 immunochemistry had the highest PPV, 20%, but 13% specimen inadequacy. Conclusions: PHS with reflex HPV16/18-genotyping had fewer unnecessary colposcopies and (if confirmed) could be a potential alternative to Co-Testing in WLWH.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1529-1537 |
| Number of pages | 9 |
| Journal | Clinical Infectious Diseases |
| Volume | 72 |
| Issue number | 9 |
| DOIs | |
| State | Published - May 1 2021 |
Keywords
- HIV
- cervical cancer screening
- human papillomavirus (HPV)
- p16/Ki-67
- primary HPV screening
ASJC Scopus subject areas
- Microbiology (medical)
- Infectious Diseases
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Primary HPV and Molecular Cervical Cancer Screening in US Women Living With Human Immunodeficiency Virus. / Strickler, Howard D.; Keller, Marla J.; Hessol, Nancy A.; Eltoum, Isam Eldin; Einstein, Mark H.; Castle, Philip E.; Massad, L. Stewart; Flowers, Lisa; Rahangdale, Lisa; Atrio, Jessica M.; Ramirez, Catalina; Minkoff, Howard; Adimora, Adaora A.; Ofotokun, Igho; Colie, Christine; Huchko, Megan J.; Fischl, Margaret; Wright, Rodney; D'Souza, Gypsyamber; Leider, Jason; Diaz, Olga; Sanchez-Keeland, Lorraine; Shrestha, Sadeep; Xie, Xianhong; Xue, Xiaonan; Anastos, Kathryn; Palefsky, Joel M.; Burk, Robert D.
In: Clinical Infectious Diseases, Vol. 72, No. 9, 01.05.2021, p. 1529-1537.Research output: Contribution to journal › Article › peer-review
}
TY - JOUR
T1 - Primary HPV and Molecular Cervical Cancer Screening in US Women Living With Human Immunodeficiency Virus
AU - Strickler, Howard D.
AU - Keller, Marla J.
AU - Hessol, Nancy A.
AU - Eltoum, Isam Eldin
AU - Einstein, Mark H.
AU - Castle, Philip E.
AU - Massad, L. Stewart
AU - Flowers, Lisa
AU - Rahangdale, Lisa
AU - Atrio, Jessica M.
AU - Ramirez, Catalina
AU - Minkoff, Howard
AU - Adimora, Adaora A.
AU - Ofotokun, Igho
AU - Colie, Christine
AU - Huchko, Megan J.
AU - Fischl, Margaret
AU - Wright, Rodney
AU - D'Souza, Gypsyamber
AU - Leider, Jason
AU - Diaz, Olga
AU - Sanchez-Keeland, Lorraine
AU - Shrestha, Sadeep
AU - Xie, Xianhong
AU - Xue, Xiaonan
AU - Anastos, Kathryn
AU - Palefsky, Joel M.
AU - Burk, Robert D.
N1 - Funding Information: Potential conflicts of interest. P. E. C. has received commercial HPV tests for research at a reduced or no cost from Roche, Cepheid, BD, and Arbor Vita Corporation. J. M. P. has been compensated financially as a member of a Merck data and safety monitoring board for HPV vaccines, and has received travel support from Merck; as a consultant for Vir Biotechnologies received fees and stock options; stock options from Virion Therapeutics; Antiva Biosences provided grant support; with Ubiome participated in a scientific advisory board and received stock options; with Vaccitech participated in a scientific advisory board and received stock options; with Jannsen Pharmaceuticals was an invited speaker. H. D. S. has received free blinded testing using HPV E6/E7 protein assays by Arbor Vista, p16/Ki67 cytology by MTM Laboratories/Ventura–Roche, and MCM-2/TOP2A cytology by BD Diagnostics. M. E. has advised or participated in educational speaking activities, but does not receive an honorarium from any companies. In specific cases, his employers have received payment for his time spent for these activities from Photocure, Advaxis, Johnson & Johnson, PDS, Becton-Dickenson, Pfizer, Inovio, Astra Zeneca, Merck, Hologic, Papivax, Cynvec, and Altum Pharma. If travel required for meetings with industry, the company pays for Dr Einstein’s travel expenses. Rutgers has received grant funding for research-related costs of clinical trials that Dr Einstein has been the overall or local PI within the past 12 months from Roche, Johnson & Johnson, Pfizer, AstraZeneca, Advaxis, and Inovio. M. F. received grants from the University Miami School Medicine, outside the submitted work. A. A. reports grants from NIH, during the conduct of the study; personal fees from Merck, Viiv, Gilead; and grants from Gilead, outside the submitted work. K. A. reports grants from NIH during the conduct of the study; and grants from NIH (NIAID) and NIH (NCI, Fogarty), outside the submitted work. R. B. reports grants from NIH. N. H. reports grants from National Cancer Institute, during the conduct of the study. M. K. reports grants from NIH, during the conduct of the study. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed. Funding Information: Acknowledgments and Financial support. Cervical specimen collection, cytopathology, histopathology, HPV testing, and the current analyses were supported by the National Cancer Institute (NCI) (grant numbers R01-CA-085178 and R01-CA-174634 to H. D. S. and P30-CA-013330). MTM/Roche Laboratories AG, provided free p16/Ki-67 (CINTech+) testing, although the company was masked to patient diagnosis and had no control of the data generated in this study or this report. All other data in this manuscript were collected by the Women’s Interagency HIV Study (WIHS). The contents of this publication are solely the responsibility of the authors and do not represent the official views of the National Institutes of Health (NIH). WIHS (Principal Investigators): UAB-MS WIHS (Mirjam-Colette Kempf and Deborah Konkle-Parker), U01-AI-103401; Atlanta WIHS (Ighovwerha Ofotokun and Gina Wingood), U01-AI-103408; Bronx WIHS (Kathryn Anastos, Anjali Sharma), U01-AI-035004; Brooklyn WIHS (Howard Minkoff and Deborah Gustafson), U01-AI-031834; Chicago WIHS (Mardge Cohen and Audrey French), U01-AI-034993; Metropolitan Washington WIHS (Seble Kassaye), U01-AI-034994; Miami WIHS (Margaret Fischl and Lisa Metsch), U01-AI-103397; UNC WIHS (Adaora Adimora), U01-AI-103390; Connie Wofsy Women’s HIV Study, Northern California (Ruth Greenblatt, Bradley Aouizerat, and Phyllis Tien), U01-AI-034989; WIHS Data Management and Analysis Center (Stephen Gange and Elizabeth Golub), U01-AI-042590; Southern California WIHS (Joel Milam), U01-HD-032632 (WIHS I—WIHS IV). The WIHS is funded primarily by the National Institute of Allergy and Infectious Diseases (NIAID), with additional co-funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), the National Cancer Institute (NCI), the National Institute on Drug Abuse (NIDA), and the National Institute on Mental Health (NIMH). Targeted supplemental funding for specific projects is also provided by the National Institute of Dental and Craniofacial Research (NIDCR), the National Institute on Alcohol Abuse and Alcoholism (NIAAA), the National Institute on Deafness and other Communication Disorders (NIDCD), and the NIH Office of Research on Women’s Health. WIHS data collection is also supported by UL1-TR000004 (UCSF CTSA), UL1-TR000454 (Atlanta CTSA), and P30-AI-050410 (UNC CFAR). Funding Information: Cervical specimen collection, cytopathology, histopathology, HPV testing, and the current analyses were supported by the National Cancer Institute (NCI) (grant numbers R01-CA-085178 and R01-CA-174634 to H. D. S. and P30-CA-013330). MTM/Roche Laboratories AG, provided free p16/Ki-67 (CINTech+) testing, although the company was masked to patient diagnosis and had no control of the data generated in this study or this report. All other data in this manuscript were collected by the Women's Interagency HIV Study (WIHS). The contents of this publication are solely the responsibility of the authors and do not represent the official views of the National Institutes of Health (NIH). WIHS (Principal Investigators): UAB-MS WIHS (Mirjam- Colette Kempf and Deborah Konkle-Parker), U01-AI-103401; Atlanta WIHS (Ighovwerha Ofotokun and Gina Wingood), U01-AI-103408; Bronx WIHS (Kathryn Anastos, Anjali Sharma), U01-AI-035004; Brooklyn WIHS (Howard Minkoff and Deborah Gustafson), U01-AI-031834; Chicago WIHS (Mardge Cohen and Audrey French), U01-AI-034993; Metropolitan Washington WIHS (Seble Kassaye), U01-AI-034994; Miami WIHS (Margaret Fischl and Lisa Metsch), U01-AI-103397; UNC WIHS (Adaora Adimora), U01-AI-103390; Connie Wofsy Women's HIV Study, Northern California (Ruth Greenblatt, Bradley Aouizerat, and Phyllis Tien), U01-AI-034989; WIHS Data Management and Analysis Center (Stephen Gange and Elizabeth Golub), U01-AI-042590; Southern California WIHS (Joel Milam), U01-HD-032632 (WIHS I - WIHS IV). The WIHS is funded primarily by the National Institute of Allergy and Infectious Diseases (NIAID), with additional co-funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), the National Cancer Institute (NCI), the National Institute on Drug Abuse (NIDA), and the National Institute on Mental Health (NIMH). Targeted supplemental funding for specific projects is also provided by the National Institute of Dental and Craniofacial Research (NIDCR), the National Institute on Alcohol Abuse and Alcoholism (NIAAA), the National Institute on Deafness and other Communication Disorders (NIDCD), and the NIH Office of Research on Women's Health. WIHS data collection is also supported by UL1-TR000004 (UCSF CTSA), UL1-TR000454 (Atlanta CTSA), and P30-AI-050410 (UNC CFAR). Publisher Copyright: © 2020 The Author(s) 2020.
PY - 2021/5/1
Y1 - 2021/5/1
N2 - Background: Primary human papillomavirus (HPV) screening (PHS) utilizes oncogenic human papillomavirus (oncHPV) testing as the initial cervical cancer screening method and typically, if positive, additional reflex-triage (eg, HPV16/18-genotyping, Pap testing). While US guidelines support PHS usage in the general population, PHS has been little studied in women living with HIV (WLWH). Methods: We enrolled n = 865 WLWH (323 from the Women's Interagency HIV Study [WIHS] and 542 from WIHS-affiliated colposcopy clinics). All participants underwent Pap and oncHPV testing, including HPV16/18-genotyping. WIHS WLWH who tested oncHPV[+] or had cytologic atypical squamous cells of undetermined significance or worse (ASC-US+) underwent colposcopy, as did a random 21% of WLWH who were oncHPV[-]/Pap[-] (controls). Most participants additionally underwent p16/Ki-67 immunocytochemistry. Results: Mean age was 46 years, median CD4 was 592 cells/μL, 95% used antiretroviral therapy. Seventy WLWH had histologically-determined cervical intraepithelial neoplasia grade 2 or greater (CIN-2+), of which 33 were defined as precancer (ie, [i] CIN-3+ or [ii] CIN-2 if concurrent with cytologic high grade squamous intraepithelial lesions [HSILs]). PHS had 87% sensitivity (Se) for precancer, 9% positive predictive value (PPV), and a 35% colposcopy referral rate (Colpo). "PHS with reflex HPV16/18-genotyping and Pap testing"had 84% Se, 16% PPV, 30% Colpo. PHS with only HPV16/18-genotyping had 24% Colpo. "Concurrent oncHPV and Pap Testing"(Co-Testing) had 91% Se, 12% PPV, 40% Colpo. p16/Ki-67 immunochemistry had the highest PPV, 20%, but 13% specimen inadequacy. Conclusions: PHS with reflex HPV16/18-genotyping had fewer unnecessary colposcopies and (if confirmed) could be a potential alternative to Co-Testing in WLWH.
AB - Background: Primary human papillomavirus (HPV) screening (PHS) utilizes oncogenic human papillomavirus (oncHPV) testing as the initial cervical cancer screening method and typically, if positive, additional reflex-triage (eg, HPV16/18-genotyping, Pap testing). While US guidelines support PHS usage in the general population, PHS has been little studied in women living with HIV (WLWH). Methods: We enrolled n = 865 WLWH (323 from the Women's Interagency HIV Study [WIHS] and 542 from WIHS-affiliated colposcopy clinics). All participants underwent Pap and oncHPV testing, including HPV16/18-genotyping. WIHS WLWH who tested oncHPV[+] or had cytologic atypical squamous cells of undetermined significance or worse (ASC-US+) underwent colposcopy, as did a random 21% of WLWH who were oncHPV[-]/Pap[-] (controls). Most participants additionally underwent p16/Ki-67 immunocytochemistry. Results: Mean age was 46 years, median CD4 was 592 cells/μL, 95% used antiretroviral therapy. Seventy WLWH had histologically-determined cervical intraepithelial neoplasia grade 2 or greater (CIN-2+), of which 33 were defined as precancer (ie, [i] CIN-3+ or [ii] CIN-2 if concurrent with cytologic high grade squamous intraepithelial lesions [HSILs]). PHS had 87% sensitivity (Se) for precancer, 9% positive predictive value (PPV), and a 35% colposcopy referral rate (Colpo). "PHS with reflex HPV16/18-genotyping and Pap testing"had 84% Se, 16% PPV, 30% Colpo. PHS with only HPV16/18-genotyping had 24% Colpo. "Concurrent oncHPV and Pap Testing"(Co-Testing) had 91% Se, 12% PPV, 40% Colpo. p16/Ki-67 immunochemistry had the highest PPV, 20%, but 13% specimen inadequacy. Conclusions: PHS with reflex HPV16/18-genotyping had fewer unnecessary colposcopies and (if confirmed) could be a potential alternative to Co-Testing in WLWH.
KW - HIV
KW - cervical cancer screening
KW - human papillomavirus (HPV)
KW - p16/Ki-67
KW - primary HPV screening
UR - http://www.scopus.com/inward/record.url?scp=85103476887&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85103476887&partnerID=8YFLogxK
U2 - 10.1093/cid/ciaa1317
DO - 10.1093/cid/ciaa1317
M3 - Article
C2 - 32881999
AN - SCOPUS:85103476887
VL - 72
SP - 1529
EP - 1537
JO - Clinical Infectious Diseases
JF - Clinical Infectious Diseases
SN - 1058-4838
IS - 9
ER -