Therapy for cervical intraepithelial neoplasia-2 (CIN2), a potential precursor of invasive cervical cancer, can include resection of affected tissue which can prevent progression but result in cervical incompetence and complications during pregnancy. We sought to characterize the natural history of CIN2 among HIV-positive women of childbearing age.
126 biopsy-confirmed CIN2-diagnosed women under age 46 (109 HIV-positive and 17 HIV-negative) were included from the multi-site, observational Women’s Interagency HIV Study. Kaplan-Meier curves and Cox proportional hazards models were used to assess time to CIN2 progression (CIN3+) with CD4+ T cell and HIV RNA levels analyzed as time dependent covariates (SASv9.3).
CIN2-diagnosed women were primarily Black (56.4%), current smokers (51.6%), with a median age of 32 years and contributed 2,558 semi-annual visits over a median of 10 years. Among 109 HIV-positive women with CIN2, 66 (60.6%) did not receive CIN2 treatment during follow-up. CIN2 treated and untreated HIV-positive women did not differ in median follow-up time, colposcopy findings, age, CD4+ count, HIV RNA level, or combination antiretroviral therapy (cART) use. Only 21% of HIV-positive women showed CIN2 progression within the median 10-year follow-up. Three untreated women progressed to cancer. CIN2 progression rates were not significantly different in HIV-positive women treated versus untreated for CIN2 at 2 years (11.1% vs. 5.2%) or 5 years (14.8% vs. 16.2%) post-CIN2 diagnosis. Propensity weighting did not affect findings. Median time to CIN2 progression was not significantly different between treated and untreated HIV-positive women (5.8 vs. 9.0 years, p=0.14). Use of cART was associated with ~ 80% decrease in CIN2 progression (hazard ratio (aHR) 0.20; 95% CI 0.05, 0.71), adjusting for CIN2 treatment, CD4+ count, and HIV RNA levels. Similarly, each increase of 100 CD4+ T cells was associated with ~ 30% decrease in CIN2 progression (aHR=0.68; 95% CI 0.53, 0.85), adjusting for CIN2 treatment, cART use, and HIV RNA levels.
Progression of CIN2 is uncommon in HIV-positive women, regardless of treatment. For HIV-positive women of childbearing age who are well controlled on cART and considering pregnancy, short-term conservative management of CIN2 with close monitoring may be an alternative to immediate resection. Further studies are planned to determine the role of HPV type on cervical disease progression.