Intensive cervical cancer screening may be appropriate for HIV-positive women with a CD4 count below 500 and for immunosuppressed solid organ transplant recipients--but not for HIV-positive women with more CD4s or for women on immunosuppressive therapy . Those conclusions arose from a 121,000-woman case-control study in the Kaiser Permanente healthcare system in northern California. Women with HIV had twice higher odds of advanced cervical intraepithelial neoplasia (CIN) or cervical cancer than women without HIV.
Kaiser investigators conducted this study to get a better fix on which HIV-positive and other immunosuppressed women need intensive cervical cancer screening. The researchers considered all women 18 to 70 years old in care between July 1996 and June 2014. Cases were women with incident (newly diagnosed) CIN 2, CIN3, or cervical cancer, designated CIN2+ or CIN3+. For every case the researchers identified 5 women without CIN2+ matched by age, diagnosis date of the case, years in the Kaiser system, and date of first Kaiser Pap test. They analyzed risk of CIN2+, CIN3+, and cancer in (1) all HIV-positive (versus negative) women, (2) HIV-positive (versus negative) women grouped by recent CD4 count below 200, 200 to 499, and 500 or higher, and (3) women with non-HIV immunosuppression, including immunosuppressive therapy (such as calcineurin inhibitors and corticosteroids) in the last 18 months (versus no therapy) and solid-organ transplant (versus no transplant).
Cases were 20,146 women with CIN2+, including 11,275 with CIN3+ and 646 with cervical cancer. Because of matching, cases and controls had the same average age (36) and similar numbers of years in the Kaiser system (6.4 and 6.6 years). Cases and controls were also similar in proportions of whites (54% and 49%), Hispanics (20% and 21%), and blacks (8% and 9%). Cases included a higher proportion of smokers (19% versus 13%). About 2% in each group had been vaccinated against HPV.
Cases included 36 women with HIV (0.18% of 20,146) and controls included 79 HIV-positive women (0.08% of 100,780). All of this percentage difference lay among women with a CD4 count below 500. The proportion of HIV-positive cases with a recent CD4 count above 500 was 0.04%, exactly the same proportion of HIV-positive controls with a recent CD4 count above 500. Numbers of cases and controls with recent immunosuppressive therapy were 1370 (6.8% of cases) and 6429 (6.4% of controls). Cases included 51 transplant recipients (0.25% of cases) and controls included 69 transplant recipients (0.07% of controls).
In adjusted analyses, compared with HIV-negative women, HIV-positive women had 2.0-fold higher odds of CIN2+ and 2.3-fold higher odds of CIN3+. HIV-positive women with a recent CD4 count under 200 CD4s had 5.7-fold higher odds of CIN2+ and women with 200 to 499 CD4s had 3.0-fold higher odds. But risk of CIN2+ was not greater in HIV-positive women with 500 or more CD4s compared with HIV-negative women. The same held true for the CIN3+ analysis: Odds were 5.4-fold higher with a recent CD4 count under 200 CD4s and 3.6-fold higher with 200 to 499 CD4s, but risk was no greater in women with 500 or more CD4s.
Women with a solid-organ transplant had independently higher odds of CIN2+ (3.3-fold) and CIN3+ (2.9-fold). But women on immunosuppressive therapy did not have higher odds of CIN2+ or CIN3+.
Among the 646 women in whom cancer developed, 2 (0.3%) had HIV compared with 0 of 3230 matched controls; 34 of 646 women with cancer (5.3%) had recent immunosuppressive therapy compared with 156 of the 3230 matched controls (4.8%); and no woman with cancer had a solid-organ transplant compared with 4 matched controls (0.1%).
The Kaiser team concluded that HIV-positive women had 2-fold higher odds of CIN2+ and CIN3+, but these higher odds applied only to women with a recent CD4 count below 500. Solid-organ transplantation conferred 3-fold higher odds of CIN2+ and CIN3+, but recent immunosuppressive therapy did not affect CIN2+ risk.
Take home message: more frequent cervical cancer screening may be needed only for subsets of women with HIV and non-HIV immunosuppression, including HIV-positive women with a CD4 count below 500 and solid-organ transplant recipients. They suggested that future studies addressing these issues "should take into account harms and costs anticipated with various screening strategies."
1. Silverberg MJ, Leyden W, Steven Gregorich S, et al. Is intensive cervical cancer screening justified in immunosuppressed women? Conference on Retroviruses and Opportunistic Infections (CROI), February 22-25, 2016, Boston. Abstract 162.