High prevalence of cancerous and pre-cancerous cervical cell changes in HIV-positive women in Zambian study

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HIV-positive women in Zambia have a very high rate of cervical lesions and cancer, according to a study presented at the Sixteenth International AIDS Conference in Toronto on Tuesday August 15th

Cervical cancer is the most common cancer among women in developing countries -- with the highest prevalence in sub-Saharan Africa and South America – and is responsible for an estimated 275,000 deaths worldwide each year.

Cervical cancer has been classified as an AIDS-defining illness since the early 1990s. Past research has shown that women with HIV are more likely than HIV-negative women to be infected with human papilloma virus (HPV), and are more likely to develop squamous intraepithelial lesions (SIL), or pre-cancerous cell changes. They also have a faster rate of progression from low-grade to high-grade SIL or cancer, and are more likely to experience recurrence after treatment.

Glossary

cervix

The cervix is the neck of the womb, at the top of the vagina. This tight ‘collar’ of tissue closes off the womb except during childbirth. Cancerous changes are most likely in the transformation zone where the vaginal epithelium (lining) and the lining of the womb meet.

squamous intraepithelial lesion (SIL)

This term is used to describe the detection of abnormal cells that have been ‘transformed’ by HPV into a possibly pre-cancerous state. According to the degree of cell change this will be called low-grade or high-grade SIL (LSIL or HSIL). If SIL is detected, a colposcopy will usually be ordered.

human papilloma virus (HPV)

Some strains of this virus cause warts, including genital and anal warts. Other strains are responsible for cervical cancer, anal cancer and some cancers of the penis, vagina, vulva, urethra, tongue and tonsils.

lesions

Small scrapes, sores or tears in tissue. Lesions in the vagina or rectum can be cellular entry points for HIV.

invasive

In medical terms, going inside the body.

In wealthy countries, invasive cervical cancer (ICC) is not more common among HIV-positive compared with HIV-negative women, largely due to routine Pap screening that detects early cervical lesions at a treatable stage. However, as HIV-positive women live thanks to potent HIV therapy in resource-limited countries where such screening is not readily available, they may survive long enough for SIL to progress to invasive cancer.

Groesbeck Parham from the University of Alabama and the Center for Infectious Disease Research in Zambia presented the results from a study of the prevalence and predictors of pre-cancerous cervical changes in 150 non-pregnant, HIV-infected women receiving care in Lusaka, Zambia. The women received pelvic examinations, and cervical cell samples were analyzed using the ThinPrep Pap Test and tested for HPV using a PCR assay.

In this cross-sectional study, the median age of the participants was 36 years. Only 2% of the women smoked tobacco, a known risk factor for cervical cancer. The average age of first sexual intercourse was 18 years, and 17% had six or more lifetime sexual partners (another known risk factor); only 25% reported consistent condom use. The mean CD4 cell count was 161 cells/mm3. About three-quarters of the women were on antiretroviral therapy, but most had just started within the previous six months.

Only 6% of the women had completely normal cervical cell samples, leaving more than 90% with some degree of abnormality. Low-grade SIL was present in 23%, while 34% had high-grade SIL, and 19% had lesions suggesting cervical cancer. The remaing 17% of women had lesions of indeterminate status. Most women (85%) had at least one high-risk HPV type (for example, 16 or 18) associated with cervical cancer.

In their initial analysis, the researchers found that age, low CD4 cell count, and the presence of any high-risk HPV types were significantly associated with high-grade SIL or cancer. There appeared to be a linear relationship between lower CD4 counts and higher-grade cervical lesions. In a multivariate analysis that controlled for potential confounding factors, women with high-risk HPV types wereapproximately twelve times more likely to have high-grade SIL or cancer (p = 0.02).

The prevalence of SIL and cervical cancer in this study was among the highest ever reported, which Parham attributed to severe immune suppression in this population; he also suggested that poor nutrition might play a role. Because most women had been on potent antiretroviral therapy for such a short time, it was not possible to determine the effect of therapy and CD4 cell recovery

The researchers concluded that, “It is essential to develop, implement, and evaluate cost-effective screening tests and appropriate treatment protocols for HIV-infected women in resource limited settings who, on antiretroviral therapy, may live long enough to develop HPV-induced invasive cervical cancer.”

Underscoring this point, one of the HIV-positive women who received cervical screening and treatment at the researchers’ clinic spoke during the discussion period, urging funders to devote more resources to similar programmes; her sister, she said, received the screening too late and died of cervical cancer.

References

Parham G et al. Prevalence and predictors of squamous intraepithelial lesions of the cervix in HIV-infected women in Lusaka, Zambia. Sixteenth International AIDS Conference, Toronto, abstract TUAB0303, 2006.