Antiretroviral Therapy and Detection of High-grade Cervical Intraepithelial Neoplasia (CIN2+) at Post-CIN Management Follow-up Among Women Living With Human Immunodeficiency Virus: A Systematic Review and Meta-Analysis

Abstract

Background We evaluated the association of antiretroviral therapy (ART), CD4+ count and human immunodeficiency virus (HIV) plasma viral load (PVL) on high-grade cervical intraepithelial neoplasia (CIN2+) detection at follow-up after CIN management among women living with HIV (WLHIV). Methods Medline, Embase, Global Health, and PubMed were searched from 1 January 1996 to 15 January 2020. Eligible studies investigated the association of ART, CD4+ count, or HIV PVL on histology-confirmed CIN2+ detection at follow-up. Summary estimates were obtained using random-effects meta-analyses; heterogeneity was examined using I2 statistic. PROSPERO registration: CRD42018115631. Results Eight studies representing 9 populations were identified, including 1452 WLHIV followed between 6 and 33 months post-CIN management. Pooled data from 8 populations (n = 1408) suggested weak evidence of a decreased risk of CIN2+ detection at follow-up among ART users compared to ART-naive women (crude odds ratio [cOR] = 0.70, 95% confidence interval [CI]: .36–1.36; I2 = 64.5%, P = .006; adjusted risk ratio [aRR] from 3 studies = 0.66, 95% CI: .20–2.24; I2 = 78.7%, P = .009). A significant association was observed in high-income countries (cOR = 0.24, 95% CI: .13–.45; I2 = 0.0%, P = .77) but not in low and middle-income countries (cOR = 1.13, 95% CI: .67–1.92; I2 = 18.8%, P = .30). In 3 populations, ART users with HIV PVL <50 copies/ml were less likely to have CIN2+ detection at follow-up (vs ≥50 copies/mL: cOR = 0.55, 95% CI: .32–.94; I2 = 0.0%, P = .23). There was weak evidence of decreased CIN2+ detection at follow-up among WLHIV with higher contemporary CD4+ cell counts (≥200 cells/µL vs <200 cells/µL [cOR = 0.36, 95% CI: .04–3.13; I2 = 81.3%, P = .021]) and significant evidence among women with a higher nadir CD4+ count (≥350 cells/µl vs <200 cells/µl [adjusted hazard ratio [aHR] = 0.35, 95% CI: .15–.84; I2 = 0%, P = .64]). Conclusion ART may reduce the risk of CIN2+ detection at follow-up; this effect is most likely enhanced by a combination of adequate HIV control and excisional CIN treatment. Our findings support recommendations of early ART and the integration of CIN2+ screening and management into HIV care.

Can we increase the cervical cancer screening interval with an HPV test for women living with HIV? Results of a cohort study from Maharashtra, India

“…24 Our cohort of treated women has been very rigorously evaluated with HPV detection test combined with colposcopy at follow-up and the follow up duration (median IQR 3.1, 95% CI 2.6-3.7) was longer than most of the studies evaluating treatment of CIN 2/3. 25 Among the HPV positive women at baseline treated for CIN 1 with thermal ablation, 11.8% women in our cohort progressed to a higher grade abnormality. Complete regression of disease on colposcopy and histopathology was observed in 65.6% of the HPV positive WHIV who had high-grade CIN and were treated with thermal ablation.…”

“…In the high-income countries, ART with adequate control of HIV (HIV PVL <50 copies/ml) was shown to reduce the subsequent risk of CIN 2+ disease but the same was not seen in low-and middle-income countries. 25 The strongest risk factor for CIN 2 or worse disease was persistent HPV infection. Women who cleared HPV infection were also at a substantial risk of developing CIN 2+ lesions.…”

Cervical Cancer Screening Cascade for women living with HIV: A cohort study from Zimbabwe

“…No other studies included re-screening measures. Furthermore, our cascade focuses on WLHIV and assessing the full continuum of care for this high-risk group offers insights into their specific screening needs and may allow more riskstratified approaches to be developed in the future [31,32].…”

“…The risk of residual or recurrent cervical disease is higher in WLHIV if they are treated with cryotherapy instead of LEEP [34,35], and also when the excision is incomplete [36,37], but post-treatment follow-up recommendations do not vary by treatment modality. ART status and immunodeficiency may also be associated with differences in CIN treatment outcomes [31]. The relatively low screening test accuracy of VIAC may account for over-treatment and persistent false-positive tests at re-screening [38].…”

Should the management of high grade cervical squamous intraepithelial lesion (HSIL) be different in HIV-positive women?

“…Comparing HIV women with treatment failure and those without, we observed that shorter duration of cumulative undetectable HIV VL, or VL > 50 copies/ml at the time of HSIL treatment, higher maximum VL between time of HIV diagnosis and cervical excision, a lower CD4/CD8 ratio, lower nadir CD4 count and lower CD4 count at time of dysplasia were associated with higher rates of treatment failure. Atemnkeng et al [ 15 ] evaluated the association between cART, viral load, CD4 count and detection of CIN 2 + at follow-up. They observed that cART intake was associated with a reduced risk of CIN 2 + detection at follow-up, after excisional procedures, but not after ablative treatment, as well as in cART users with undetectable VL.…”