Women
living with HIV are more likely than HIV-negative women to have residual or
recurring abnormal cells after treatment for pre-cancerous cervical lesions,
according to research recently published in Clinical Infectious Diseases.

This systematic
review and meta-analysis found that treatment for cervical intraepithelial
neoplasia (CIN), or abnormal cells that could progress to cancer, was nearly
three times more likely to be unsuccessful in HIV-positive women. However, the
study was unable to classify women according to CD4 cell count, so it does not shed
much light on outcomes among women on antiretroviral therapy with
well-preserved immune function.

Several types of human
papillomavirus (HPV) can cause cervical, anal, oral and other cancers. Cervical
cancer is a major cause of cancer-related death for women worldwide, but it
usually is not fatal in industrialised countries thanks to regular HPV
screening and Pap tests, which allow for early treatment before abnormal cells
progress to cancer.

Studies have shown that women with
HIV are more likely than HIV-negative women to have persistent HPV infection
and to develop CIN and invasive cervical cancer. Those with lower CD4 counts,
indicating greater immune suppression, are at higher risk.

CIN lesions are graded according to
severity. Many grade 1 lesions will clear up on their own. Treatment is usually
recommended for women with grade 2 or 3 pre-cancerous lesions (also known as
high-grade squamous intraepithelial lesions, or HSIL).
This may involve destroying the abnormal cells by freezing (cryotherapy) or
heat, or cutting out a cone-shaped section of the cervix using a cold knife or
heated wire (loop electrosurgical excision procedure, or LEEP).

Pierre Debeaudrap of Université Paris
Descartes and colleagues performed a systematic review and meta-analysis of
studies looking at outcomes of cervical pre-cancer treatment in women with HIV.

Searching MEDLINE,
HIV conference abstracts and other sources in any language from January 1980 to May 2018, the researchers identified 40 eligible studies in which
HIV-positive women with confirmed cervical abnormalities were followed for at
least six months post-treatment. Four were clinical trials, 16 were
observational cohort studies and 20 were retrospective studies.

Two-thirds of the
studies were conducted in high-income countries (mostly the US) and 13 in low-
and middle-income countries (mostly in Africa); however, the low-income country
studies were larger and accounted for a majority of total participants.
Altogether, the studies included 3975 HIV-positive women. Some also included
HIV-negative women as a comparison group (total 3638). LEEP was the most
common treatment approach.

A meta-analysis of
the data found that the pooled prevalence of treatment failure among HIV-positive
women – defined as the continued presence of residual grade 2 or higher CIN, or
recurrence of high-grade CIN after treatment – was 21.4%. Half of the women had
residual or recurrent cervical abnormalities of any grade.

There was no
difference in the likelihood of treatment failure using cryotherapy (13.9%)
versus LEEP (13.8%). Failure was more likely, at 47.2%, in women with positive
margins, meaning some precancerous cells were found at the edges of the
surgically removed tissue, compared to those with negative margins (19.4%
failure). Of note, the treatment failure rate was higher in high-income (27.9%)
compared with low-income countries (14.4%).

In the ten studies
that included both HIV-positive and HIV-negative women, the women with HIV had
more than a twofold higher risk of treatment failure with grade 2 or higher
CIN (23.4% versus 9.5%, respectively; odds ratio 2.7). Further, HIV-positive
women had a fivefold higher likelihood of having post-treatment cervical abnormalities
of any grade.

“This
meta-analysis provides evidence that, even after cervical screening and
treatment, women infected with HIV remain at high risk of CIN2+/HSIL cervical
lesions,” the researchers wrote in their discussion. “In the context
of increasing effort to scale up cervical cancer screening in limited-resource
settings, these findings highlight the importance of reflecting upon the
appropriate post-treatment follow-up of this population.”

A limitation of this
analysis is that the studies did not always include information about the
women’s CD4 counts, which are known to affect cervical pre-cancer outcomes in
women with HIV. However, some of the individual studies did show
significantly more treatment failure in women with lower current or nadir
(lowest-ever) CD4 levels. Also, the studies did not consistently distinguish
between residual abnormalities – which suggest pre-cancerous cells were not
completely destroyed or removed – and relapse.

Based on these
findings, the researchers concluded, “There is strong evidence for
increased risk of treatment failure in HIV-infected women in comparison to
their HIV-negative counterparts. The only significant predictor of treatment
failure in HIV-infected women was positive margin status, but further data is
needed on long-term outcomes after ablative treatment in HIV-infected women.”