Risk of cervical precancer and cancer among HIV-infected women with normal cervical cytology and no evidence of oncogenic HPV infection

Marla J. Keller, Robert D. Burk, Xianhong Xie, Kathryn Anastos, L. Stewart Massad, Howard Minkoff, Xiaonan (Nan) Xue, Gypsyamber D'Souza, Heather Watts, Alexandra M. Levine, Philip E. Castle, Christine Colie, Joel M. Palefsky, Howard Strickler

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Abstract

Context: US cervical cancer screening guidelines for human immunodeficiency virus (HIV)-uninfected women 30 years or older have recently been revised, increasing the suggested interval between Papanicolaou (Pap) tests from 3 years to 5 years among those with normal cervical cytology (Pap test) resultswhotest negative for oncogenic human papilloma-virus (HPV). Whether a 3-year or 5-year screening interval could be used in HIV-infected women who are cytologically normal and oncogenic HPV-negative is unknown. Objective: To determine the risk of cervical precancer or cancer defined cytologically (high-grade squamous intraepithelial lesions or greater [HSIL+]) or histologically (cervical intraepithelial neoplasia 2 or greater [CIN-2+]), as 2 separate end points, in HIV-infected women and HIV-uninfected women who at baseline had a normal Pap test result and were negative for oncogenic HPV. Design, Setting, and Participants: Participants included 420 HIV-infected women and 279 HIV-uninfected women with normal cervical cytology at their enrollment in a multi-institutional US cohort of the Women's Interagency HIV Study, between October 1, 2001, and September 30, 2002, with follow-up through April 30, 2011. Semi-annual visits at 6 clinical sites included Pap testing and, if indicated, cervical biopsy. Cervicovaginal lavage specimens from enrollment were tested for HPV DNA using polymerase chain reaction. The primary analysis was truncated at 5 years of follow-up. Main Outcome Measure: Five-year cumulative incidence of cervical precancer and cancer. Results: No oncogenic HPV was detected in 369 (88% [95% CI,84%-91%]) HIV-infected women and 255 (91% [95% CI, 88%-94%]) HIV-uninfected women with normal cervical cytology at enrollment. Among these oncogenic HPV-negative women, 2 cases of HSIL+ were observed; an HIV-uninfected woman and an HIV-infected woman with a CD4 cell count of 500 cells/μL or greater. Histologic data were obtained from 4 of the 6 clinical sites. There were 6 cases of CIN-2+ in 145 HIV-uninfected women (cumulative incidence, 5% [95% CI, 1%-8%]) and 9 cases in 219 HIV-infected women (cumulative incidence, 5% [95% CI, 2%-8%]). This included 1 case of CIN-2+ in 44 oncogenic HPV-negative HIV-infected women with CD4 cell count less than 350 cells/μL (cumulative incidence,2% [95% CI, 0%-7%]), 1 case in 47 women with CD4 cell count of 350 to 499 cells/μL (cumulative incidence, 2% [95% CI, 0%-7%]), and 7 cases in 128 women with CD4 cell count of 500 cells/μL or greater (cumulative incidence, 6% [95% CI, 2%-10%]). One HIV-infected and 1 HIV-uninfected woman had CIN-3, but none had cancer. Conclusion: The 5-year cumulative incidence of HSIL+ and CIN-2+ was similar in HIV-infected women and HIV-uninfected women who were cytologically normal and oncogenic HPV-negative at enrollment.

Original languageEnglish (US)
Pages (from-to)362-369
Number of pages8
JournalJAMA - Journal of the American Medical Association
Volume308
Issue number4
DOIs
StatePublished - Jul 25 2012

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Papillomaviridae
Oncogenic Viruses
Virus Diseases
Uterine Cervical Neoplasms
Cell Biology
HIV
CD4 Lymphocyte Count
Papanicolaou Test
Incidence

ASJC Scopus subject areas

  • Medicine(all)

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Risk of cervical precancer and cancer among HIV-infected women with normal cervical cytology and no evidence of oncogenic HPV infection. / Keller, Marla J.; Burk, Robert D.; Xie, Xianhong; Anastos, Kathryn; Massad, L. Stewart; Minkoff, Howard; Xue, Xiaonan (Nan); D'Souza, Gypsyamber; Watts, Heather; Levine, Alexandra M.; Castle, Philip E.; Colie, Christine; Palefsky, Joel M.; Strickler, Howard.

In: JAMA - Journal of the American Medical Association, Vol. 308, No. 4, 25.07.2012, p. 362-369.

Research output: Contribution to journalArticle

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title = "Risk of cervical precancer and cancer among HIV-infected women with normal cervical cytology and no evidence of oncogenic HPV infection",
abstract = "Context: US cervical cancer screening guidelines for human immunodeficiency virus (HIV)-uninfected women 30 years or older have recently been revised, increasing the suggested interval between Papanicolaou (Pap) tests from 3 years to 5 years among those with normal cervical cytology (Pap test) resultswhotest negative for oncogenic human papilloma-virus (HPV). Whether a 3-year or 5-year screening interval could be used in HIV-infected women who are cytologically normal and oncogenic HPV-negative is unknown. Objective: To determine the risk of cervical precancer or cancer defined cytologically (high-grade squamous intraepithelial lesions or greater [HSIL+]) or histologically (cervical intraepithelial neoplasia 2 or greater [CIN-2+]), as 2 separate end points, in HIV-infected women and HIV-uninfected women who at baseline had a normal Pap test result and were negative for oncogenic HPV. Design, Setting, and Participants: Participants included 420 HIV-infected women and 279 HIV-uninfected women with normal cervical cytology at their enrollment in a multi-institutional US cohort of the Women's Interagency HIV Study, between October 1, 2001, and September 30, 2002, with follow-up through April 30, 2011. Semi-annual visits at 6 clinical sites included Pap testing and, if indicated, cervical biopsy. Cervicovaginal lavage specimens from enrollment were tested for HPV DNA using polymerase chain reaction. The primary analysis was truncated at 5 years of follow-up. Main Outcome Measure: Five-year cumulative incidence of cervical precancer and cancer. Results: No oncogenic HPV was detected in 369 (88{\%} [95{\%} CI,84{\%}-91{\%}]) HIV-infected women and 255 (91{\%} [95{\%} CI, 88{\%}-94{\%}]) HIV-uninfected women with normal cervical cytology at enrollment. Among these oncogenic HPV-negative women, 2 cases of HSIL+ were observed; an HIV-uninfected woman and an HIV-infected woman with a CD4 cell count of 500 cells/μL or greater. Histologic data were obtained from 4 of the 6 clinical sites. There were 6 cases of CIN-2+ in 145 HIV-uninfected women (cumulative incidence, 5{\%} [95{\%} CI, 1{\%}-8{\%}]) and 9 cases in 219 HIV-infected women (cumulative incidence, 5{\%} [95{\%} CI, 2{\%}-8{\%}]). This included 1 case of CIN-2+ in 44 oncogenic HPV-negative HIV-infected women with CD4 cell count less than 350 cells/μL (cumulative incidence,2{\%} [95{\%} CI, 0{\%}-7{\%}]), 1 case in 47 women with CD4 cell count of 350 to 499 cells/μL (cumulative incidence, 2{\%} [95{\%} CI, 0{\%}-7{\%}]), and 7 cases in 128 women with CD4 cell count of 500 cells/μL or greater (cumulative incidence, 6{\%} [95{\%} CI, 2{\%}-10{\%}]). One HIV-infected and 1 HIV-uninfected woman had CIN-3, but none had cancer. Conclusion: The 5-year cumulative incidence of HSIL+ and CIN-2+ was similar in HIV-infected women and HIV-uninfected women who were cytologically normal and oncogenic HPV-negative at enrollment.",
author = "Keller, {Marla J.} and Burk, {Robert D.} and Xianhong Xie and Kathryn Anastos and Massad, {L. Stewart} and Howard Minkoff and Xue, {Xiaonan (Nan)} and Gypsyamber D'Souza and Heather Watts and Levine, {Alexandra M.} and Castle, {Philip E.} and Christine Colie and Palefsky, {Joel M.} and Howard Strickler",
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language = "English (US)",
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pages = "362--369",
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TY - JOUR

T1 - Risk of cervical precancer and cancer among HIV-infected women with normal cervical cytology and no evidence of oncogenic HPV infection

AU - Keller, Marla J.

AU - Burk, Robert D.

AU - Xie, Xianhong

AU - Anastos, Kathryn

AU - Massad, L. Stewart

AU - Minkoff, Howard

AU - Xue, Xiaonan (Nan)

AU - D'Souza, Gypsyamber

AU - Watts, Heather

AU - Levine, Alexandra M.

AU - Castle, Philip E.

AU - Colie, Christine

AU - Palefsky, Joel M.

AU - Strickler, Howard

PY - 2012/7/25

Y1 - 2012/7/25

N2 - Context: US cervical cancer screening guidelines for human immunodeficiency virus (HIV)-uninfected women 30 years or older have recently been revised, increasing the suggested interval between Papanicolaou (Pap) tests from 3 years to 5 years among those with normal cervical cytology (Pap test) resultswhotest negative for oncogenic human papilloma-virus (HPV). Whether a 3-year or 5-year screening interval could be used in HIV-infected women who are cytologically normal and oncogenic HPV-negative is unknown. Objective: To determine the risk of cervical precancer or cancer defined cytologically (high-grade squamous intraepithelial lesions or greater [HSIL+]) or histologically (cervical intraepithelial neoplasia 2 or greater [CIN-2+]), as 2 separate end points, in HIV-infected women and HIV-uninfected women who at baseline had a normal Pap test result and were negative for oncogenic HPV. Design, Setting, and Participants: Participants included 420 HIV-infected women and 279 HIV-uninfected women with normal cervical cytology at their enrollment in a multi-institutional US cohort of the Women's Interagency HIV Study, between October 1, 2001, and September 30, 2002, with follow-up through April 30, 2011. Semi-annual visits at 6 clinical sites included Pap testing and, if indicated, cervical biopsy. Cervicovaginal lavage specimens from enrollment were tested for HPV DNA using polymerase chain reaction. The primary analysis was truncated at 5 years of follow-up. Main Outcome Measure: Five-year cumulative incidence of cervical precancer and cancer. Results: No oncogenic HPV was detected in 369 (88% [95% CI,84%-91%]) HIV-infected women and 255 (91% [95% CI, 88%-94%]) HIV-uninfected women with normal cervical cytology at enrollment. Among these oncogenic HPV-negative women, 2 cases of HSIL+ were observed; an HIV-uninfected woman and an HIV-infected woman with a CD4 cell count of 500 cells/μL or greater. Histologic data were obtained from 4 of the 6 clinical sites. There were 6 cases of CIN-2+ in 145 HIV-uninfected women (cumulative incidence, 5% [95% CI, 1%-8%]) and 9 cases in 219 HIV-infected women (cumulative incidence, 5% [95% CI, 2%-8%]). This included 1 case of CIN-2+ in 44 oncogenic HPV-negative HIV-infected women with CD4 cell count less than 350 cells/μL (cumulative incidence,2% [95% CI, 0%-7%]), 1 case in 47 women with CD4 cell count of 350 to 499 cells/μL (cumulative incidence, 2% [95% CI, 0%-7%]), and 7 cases in 128 women with CD4 cell count of 500 cells/μL or greater (cumulative incidence, 6% [95% CI, 2%-10%]). One HIV-infected and 1 HIV-uninfected woman had CIN-3, but none had cancer. Conclusion: The 5-year cumulative incidence of HSIL+ and CIN-2+ was similar in HIV-infected women and HIV-uninfected women who were cytologically normal and oncogenic HPV-negative at enrollment.

AB - Context: US cervical cancer screening guidelines for human immunodeficiency virus (HIV)-uninfected women 30 years or older have recently been revised, increasing the suggested interval between Papanicolaou (Pap) tests from 3 years to 5 years among those with normal cervical cytology (Pap test) resultswhotest negative for oncogenic human papilloma-virus (HPV). Whether a 3-year or 5-year screening interval could be used in HIV-infected women who are cytologically normal and oncogenic HPV-negative is unknown. Objective: To determine the risk of cervical precancer or cancer defined cytologically (high-grade squamous intraepithelial lesions or greater [HSIL+]) or histologically (cervical intraepithelial neoplasia 2 or greater [CIN-2+]), as 2 separate end points, in HIV-infected women and HIV-uninfected women who at baseline had a normal Pap test result and were negative for oncogenic HPV. Design, Setting, and Participants: Participants included 420 HIV-infected women and 279 HIV-uninfected women with normal cervical cytology at their enrollment in a multi-institutional US cohort of the Women's Interagency HIV Study, between October 1, 2001, and September 30, 2002, with follow-up through April 30, 2011. Semi-annual visits at 6 clinical sites included Pap testing and, if indicated, cervical biopsy. Cervicovaginal lavage specimens from enrollment were tested for HPV DNA using polymerase chain reaction. The primary analysis was truncated at 5 years of follow-up. Main Outcome Measure: Five-year cumulative incidence of cervical precancer and cancer. Results: No oncogenic HPV was detected in 369 (88% [95% CI,84%-91%]) HIV-infected women and 255 (91% [95% CI, 88%-94%]) HIV-uninfected women with normal cervical cytology at enrollment. Among these oncogenic HPV-negative women, 2 cases of HSIL+ were observed; an HIV-uninfected woman and an HIV-infected woman with a CD4 cell count of 500 cells/μL or greater. Histologic data were obtained from 4 of the 6 clinical sites. There were 6 cases of CIN-2+ in 145 HIV-uninfected women (cumulative incidence, 5% [95% CI, 1%-8%]) and 9 cases in 219 HIV-infected women (cumulative incidence, 5% [95% CI, 2%-8%]). This included 1 case of CIN-2+ in 44 oncogenic HPV-negative HIV-infected women with CD4 cell count less than 350 cells/μL (cumulative incidence,2% [95% CI, 0%-7%]), 1 case in 47 women with CD4 cell count of 350 to 499 cells/μL (cumulative incidence, 2% [95% CI, 0%-7%]), and 7 cases in 128 women with CD4 cell count of 500 cells/μL or greater (cumulative incidence, 6% [95% CI, 2%-10%]). One HIV-infected and 1 HIV-uninfected woman had CIN-3, but none had cancer. Conclusion: The 5-year cumulative incidence of HSIL+ and CIN-2+ was similar in HIV-infected women and HIV-uninfected women who were cytologically normal and oncogenic HPV-negative at enrollment.

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