Incidence of cervical precancers among HIV-seropositive women

doi:10.1016/j.ajog.2014.12.003

. 2015 May;212(5):606.e1-8.

doi: 10.1016/j.ajog.2014.12.003. Epub 2014 Dec 10.

Incidence of cervical precancers among HIV-seropositive women

L Stewart Massad¹, Xianhong Xie², Gypsyamber D'Souza³, Teresa M Darragh⁴, Howard Minkoff⁵, Rodney Wright⁶, Christine Colie⁷, Lorraine Sanchez-Keeland⁸, Howard D Strickler²

Affiliations

¹ Department of Obstetrics and Gynecology, Washington University School of Medicine in St. Louis, St. Louis, MO. Electronic address: massadl@wudosis.wustl.edu.
² Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY.
³ Departments of Epidemiology and International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.
⁴ Departments of Pathology and Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Francisco, School of Medicine, San Francisco, CA.
⁵ Department of Obstetrics and Gynecology, Maimonides Medical Center, Brooklyn, NY.
⁶ Obstetrics and Gynecology, Albert Einstein College of Medicine, Bronx, NY; Department of Obstetrics and Gynecology, Montefiore Medical Center, Bronx, NY.
⁷ Department of Obstetrics and Gynecology, Georgetown University School of Medicine, Washington, DC.
⁸ Department of Medicine, University of Southern California School of Medicine, Los Angeles, CA.

PMID: 25499260
PMCID: PMC4416973
DOI: 10.1016/j.ajog.2014.12.003

Incidence of cervical precancers among HIV-seropositive women

L Stewart Massad et al. Am J Obstet Gynecol. 2015 May.

. 2015 May;212(5):606.e1-8.

doi: 10.1016/j.ajog.2014.12.003. Epub 2014 Dec 10.

Authors

L Stewart Massad¹, Xianhong Xie², Gypsyamber D'Souza³, Teresa M Darragh⁴, Howard Minkoff⁵, Rodney Wright⁶, Christine Colie⁷, Lorraine Sanchez-Keeland⁸, Howard D Strickler²

Affiliations

¹ Department of Obstetrics and Gynecology, Washington University School of Medicine in St. Louis, St. Louis, MO. Electronic address: massadl@wudosis.wustl.edu.
² Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY.
³ Departments of Epidemiology and International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.
⁴ Departments of Pathology and Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Francisco, School of Medicine, San Francisco, CA.
⁵ Department of Obstetrics and Gynecology, Maimonides Medical Center, Brooklyn, NY.
⁶ Obstetrics and Gynecology, Albert Einstein College of Medicine, Bronx, NY; Department of Obstetrics and Gynecology, Montefiore Medical Center, Bronx, NY.
⁷ Department of Obstetrics and Gynecology, Georgetown University School of Medicine, Washington, DC.
⁸ Department of Medicine, University of Southern California School of Medicine, Los Angeles, CA.

PMID: 25499260
PMCID: PMC4416973
DOI: 10.1016/j.ajog.2014.12.003

Abstract

Objective: The objective of the study was to estimate the impact of human immunodeficiency virus (HIV) infection on the incidence of high-grade cervical intraepithelial neoplasia (CIN).

Study design: HIV-seropositive and comparison seronegative women enrolled in a prospective US cohort study were followed up with semiannual Papanicolaou testing, with colposcopy for any abnormality. Histology results were retrieved to identify CIN3+ (CIN3, adenocarcinoma in situ, and cancer) and CIN2+ (CIN2 and CIN3+). Annual detection rates were calculated and risks compared using a Cox analysis. Median follow-up (interquartile range) was 11.0 (5.4-17.2) years for HIV-seronegative and 9.9 (2.5-16.0) for HIV-seropositive women.

Results: CIN3+ was diagnosed in 139 HIV-seropositive (5%) and 19 HIV-seronegative women (2%) (P<.0001), with CIN2+ in 316 (12%) and 34 (4%) (P<.0001). The annual CIN3+ detection rate was 0.6 per 100 person-years in HIV-seropositive women and 0.2 per 100 person-years in seronegative women (P<.0001). The CIN3+ detection rate fell after the first 2 years of study, from 0.9 per 100 person-years among HIV-seropositive women to 0.4 per 100 person-years during subsequent follow-up (P<.0001). CIN2+ incidence among these women fell similarly with time, from 2.5 per 100 person-years during the first 2 years after enrollment to 0.9 per 100 person-years subsequently (P<.0001). In Cox analyses controlling for age, the hazard ratio for HIV-seropositive women with CD4 counts less than 200/cmm compared with HIV-seronegative women was 8.1 (95% confidence interval, 4.8-13.8) for CIN3+ and 9.3 (95% confidence interval, 6.3-13.7) for CIN2+ (P<.0001).

Conclusion: Although HIV-seropositive women have more CIN3+ than HIV-seronegative women, CIN3+ is uncommon and becomes even less frequent after the initiation of regular cervical screening.

Keywords: cervical cancer prevention; cervical intraepithelial neoplasia; human immunodeficiency virus in women.

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Conflict of interest statement

Disclosure of interests: Dr. Darragh reported potential conflicts. These include:

Hologic: Research supplies for anal cytology, honorarium for webinar on anal cancer screening, October 2012 OncoHealth Advisory Board, Stock options, ongoing

Roche, October 2013: Honorarium paid to UCSF, October 2013

No other authors report potential financial conflicts of interest related to the study.

A study of Dr. Strickler’s involves free blinded testing using HPV E6/E7 protein assays by Arbor Vita (CA, USA), p16/Ki67 cytology by MTM Laboratories / Ventura – Roche (Mannheim, Germany), MCM-2/TOP2A cytology, BD Diagnostics (NJ, USA). No financial payments to Dr Strickler or his home institution were received.

No other authors reported potential financial conflicts of interest.

Figures

**Fig. 1**
Cumulative incidence of CIN3+ and CIN2+ among HIV seropositive and seronegative women. For both, P < 0.0001 by log-rank test.

See this image and copyright information in PMC

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References

1. Palefsky JM, Minkoff H, Kalish LA, Levine A, Sacks HS, Garcia P, Young M, Melnick S, Miotti P, Burk R. Cervicovaginal human papillomavirus infection in human immunodeficiency virus-1 (HIV)-positive and high-risk HIV-negative women. J Natl Cancer Inst. 1999;91:226–36. - PubMed
1. Massad LS, Riester KA, Anastos KM, Fruchter RG, Palefsky JM, Burk RD, Burns D, Greenblatt RM, Muderspach LI, Miotti P. Prevalence and predictors of squamous cell abnormalities in Papanicolaou smears from women infected with HIV-1. Women’s Interagency HIV Study Group. J Acquir Immune Defic Syndr. 1999;21:33–41. - PubMed
1. Massad LS, Seaberg EC, Wright RL, Darragh T, Lee YC, Colie C, Burk R, Strickler HD, Watts DH. Squamous cervical lesions in women with human immunodeficiency virus: long-term follow-up. Obstet Gynecol. 2008;111:1388–93. - PubMed
1. Massad LS, Seaberg EC, Watts DH, Hessol NA, Melnick S, Bitterman P, Anastos K, Silver S, Levine AM, Minkoff H. Low incidence of invasive cervical cancer among HIV infected US women in a prevention program. AIDS. 2004;18:109–13. - PubMed
1. Massad LS, Seaberg EC, Watts DH, Minkoff H, Levine AM, Henry D, Colie C, Darragh TM, Hessol NA. Long-term incidence of cervical cancer in women with HIV. Cancer. 2009;115:524–30. - PMC - PubMed

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[1] Palefsky JM, Minkoff H, Kalish LA, Levine A, Sacks HS, Garcia P, Young M, Melnick S, Miotti P, Burk R. Cervicovaginal human papillomavirus infection in human immunodeficiency virus-1 (HIV)-positive and high-risk HIV-negative women. J Natl Cancer Inst. 1999;91:226–36. - PubMed

[2] Palefsky JM, Minkoff H, Kalish LA, Levine A, Sacks HS, Garcia P, Young M, Melnick S, Miotti P, Burk R. Cervicovaginal human papillomavirus infection in human immunodeficiency virus-1 (HIV)-positive and high-risk HIV-negative women. J Natl Cancer Inst. 1999;91:226–36. - PubMed

[3] Massad LS, Riester KA, Anastos KM, Fruchter RG, Palefsky JM, Burk RD, Burns D, Greenblatt RM, Muderspach LI, Miotti P. Prevalence and predictors of squamous cell abnormalities in Papanicolaou smears from women infected with HIV-1. Women’s Interagency HIV Study Group. J Acquir Immune Defic Syndr. 1999;21:33–41. - PubMed

[4] Massad LS, Riester KA, Anastos KM, Fruchter RG, Palefsky JM, Burk RD, Burns D, Greenblatt RM, Muderspach LI, Miotti P. Prevalence and predictors of squamous cell abnormalities in Papanicolaou smears from women infected with HIV-1. Women’s Interagency HIV Study Group. J Acquir Immune Defic Syndr. 1999;21:33–41. - PubMed

[5] Massad LS, Seaberg EC, Wright RL, Darragh T, Lee YC, Colie C, Burk R, Strickler HD, Watts DH. Squamous cervical lesions in women with human immunodeficiency virus: long-term follow-up. Obstet Gynecol. 2008;111:1388–93. - PubMed

[6] Massad LS, Seaberg EC, Wright RL, Darragh T, Lee YC, Colie C, Burk R, Strickler HD, Watts DH. Squamous cervical lesions in women with human immunodeficiency virus: long-term follow-up. Obstet Gynecol. 2008;111:1388–93. - PubMed

[7] Massad LS, Seaberg EC, Watts DH, Hessol NA, Melnick S, Bitterman P, Anastos K, Silver S, Levine AM, Minkoff H. Low incidence of invasive cervical cancer among HIV infected US women in a prevention program. AIDS. 2004;18:109–13. - PubMed

[8] Massad LS, Seaberg EC, Watts DH, Hessol NA, Melnick S, Bitterman P, Anastos K, Silver S, Levine AM, Minkoff H. Low incidence of invasive cervical cancer among HIV infected US women in a prevention program. AIDS. 2004;18:109–13. - PubMed

[9] Massad LS, Seaberg EC, Watts DH, Minkoff H, Levine AM, Henry D, Colie C, Darragh TM, Hessol NA. Long-term incidence of cervical cancer in women with HIV. Cancer. 2009;115:524–30. - PMC - PubMed

[10] Massad LS, Seaberg EC, Watts DH, Minkoff H, Levine AM, Henry D, Colie C, Darragh TM, Hessol NA. Long-term incidence of cervical cancer in women with HIV. Cancer. 2009;115:524–30. - PMC - PubMed

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Incidence of cervical precancers among HIV-seropositive women

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Incidence of cervical precancers among HIV-seropositive women

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Conflict of interest statement

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