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Treatment or watchful waiting for cervical abnormalities in women with HIV?
Carole Leach-Lemens, 2017-02-16 06:00:00

Close monitoring of earlier-stage cervical abnormalities (CIN-2) may be preferable to treatment for many women with HIV, a US study suggests. The findings, presented at the Conference on Retroviruses and Opportunistic Infections (CROI 2017) in Seattle on Tuesday, show that CIN-2 regressed in over three-quarters of women taking antiretroviral therapy, without the need for treatment. A higher CD4 count was associated with a lower likelihood that the lesion would progress.

Cervical cancer is one of the most common causes of death and illness in women globally. Women with HIV are at increased risk of developing cervical intra-epithelial neoplasia or lesions (CIN) – changes in the cells of the cervix, sometimes referred to as 'pre-cancerous' cell changes. Women with lower CD4 cell counts are more likely to have cervical abnormalities. The risk of developing CIN is associated with infection with human papillomavirus (HPV), which is present in more than 60% of women with HIV. Lesions are graded according to severity. Many grade 1 and some grade 2 lesions will clear up without treatment, but the rate of regression or progression is unclear in women living with HIV. In the general population, CIN-2 is regressive in 30 to 40% of women, but for women with HIV rates of regression tend to be lower. Regardless of HIV status, women over the age of 25 are advised to have treatment for CIN-2.

Treatment can include removing affected tissue. While this prevents progression to cervical cancer, recent research has suggested such treatment can affect reproductive health, potentially leading to premature birth and complications during pregnancy.

Around 8500 women with HIV give birth annually in the United States. Dr Kate Michel, presenting, noted that it is important to provide guidance for those women with HIV who may delay CIN-2 treatment to improve pregnancy outcomes.  

Dr Michel and colleagues wanted to ascertain the risk of CIN-2 progression in women of reproductive age, including time to progression and factors associated with progression, with CD4 cell count and HIV viral load analysed as time-dependent covariates. The study included both women who had previously been treated for CIN-2 and those who had not.

Women under the age of 46 were included from the observational Women’s Interagency HIV Study (WIHS). The study, begun in 1993, looks at the impact and progression of HIV in women in clinical sites in and around 10 cities in the United States. It includes women living with HIV and women identified as being at high risk of HIV. A total of 116 women with biopsy-confirmed CIN-2 were included in the study. Of these, 102 were HIV positive (41 had previously had CIN-2 treatment) and 14 were HIV negative (8 had previously been treated).

With a mean age of 32 years, the majority of women were black or Hispanic, just over half were smokers and 72% had one male partner. Women with HIV were on average five years older than HIV-negative women.

CIN-2 regression, defined as biopsy-confirmed CIN-1 or no abnormalities detected by biopsy or normal Pap (cervical screening) tests across all follow-up visits, was overall (63%) the most common prognosis, independent of treatment, occurring in 62% and 71% of HIV-positive and HIV-negative women respectively.

Combination antiretroviral therapy (ART) was associated with a significant 78% decrease in CIN-2 progression. Similarly each increase of 100 CD4 cells/mm3 was associated with a significant 26% decrease in progression.

Seventeen per cent more HIV-negative women had treatment for CIN-2 than HIV-positive women. Dr Michel noted that this gap, while not statistically significant, warrants further examination of reproductive health access for women with HIV.

Overall 18% of women progressed to CIN-3 or dysplasia over a median of ten years (18% HIV-positive and 21% HIV-negative women. Median time to progression in HIV-positive women was three years (IQR: 2.4-3). No women progressed to cervical cancer.

Dr Michel concluded that for women with HIV considering pregnancy and with well-controlled viral load on ART, a short-term conservative management of CIN-2 with close monitoring provides an alternative to immediate resection.