Cervical Abnormalities and Cancer Common among HIV Positive Women in Zambia, and Recurred after Treatment in Brazil

By Liz Highleyman

Past research has shown that women with HIV are more likely than HIV negative women to be infected with human papillomavirus (HPV), and are more likely to develop pre-cancerous cell changes, known as squamous intraepithelial lesions (SIL) or cervical intraepithelial neoplasia (CIN). They also have a faster rate of progression from low-grade to high-grade SIL, are less likely to experience spontaneous regression, and are more likely to experience recurrence after treatment.

A study presented at the XVI International AIDS Conference, held last week in Toronto, found one of the highest-ever rates of cervical abnormalities and cancer among HIV positive women.

The cross-sectional study included 150 non-pregnant, HIV-infected women receiving care in Lusaka, Zambia. The women received pelvic examinations, and cervical cell samples were tested for HPV and analyzed for cellular abnormalities using the ThinPrep Pap Test.

Results

The median age of the study participants was 36 years. Only 2% smoked tobacco (a known risk factor for cervical cancer), 17% had six or more lifetime sexual partners (another known risk factor), and 25% reported consistent condom use.

The mean CD4 cell count was 161 cells/mm3.

77% were on antiretroviral therapy, but most had started HAART only within the previous six months; the remaining 23% were treatment-naive.

More than 90% of the women had some degree of cervical cell abnormality:

- Normal: 6.2%;
- Abnormal cells of undetermined significance: 17.2%;
- Low-grade SIL: 23.4%;
- High-grade SIL: 33.8%'
- Cervical cancer: 19.3%.

The most common HPV types were 52, 61, 62, and 58; many women had multiple types.

More than 85% had one or more "high-risk" types associated with cervical cancer, but many did not have the carcinogenic types 16 or 18.

In bivariate analyses, severe cervical abnormalities (high-grade SIL or cancer) were significantly associated with:
- Older age;
- Lower CD4 cell count;
- Presence of high-risk HPV types.

There appeared to be a linear relationship between decreasing CD4 cell counts and increasing grades of cervical abnormalities.

In a multivariable logistic regression analysis, high-risk HPV was an independent predictor of severe abnormalities (adjusted odds ratio 12.4; 95% CI 2.62-58.1; P = 0.02).

Because most women had been on HAART only a short time, it was not possible to determine whether antiretroviral therapy and CD4 cell recovery had an effect on progression of cervical abnormalities.

Conclusion

"The high prevalence of abnormal squamous cytology in our study is one of the highest reported in any population worldwide," the researchers concluded, suggesting that this may be due to severe immunosuppression among the women studied, and that poor nutrition may also play a role.

Recurrence after Treatment

In a related study, researchers looked at recurrence of cervical lesions after a form of treatment called the loop electrosurgical excision procedure (LEEP), which is used to excise abnormal cervical tissue.

They conducted a retrospective case-control study to analyze histopathological results from 201 women (94 HIV positive and 107 HIV negative) who underwent LEEP in Belo Horizonte, Brazil. Patients were followed for a mean of two years, with cytological and colposcopic examinations every six months.

Results

Cervical intraepithelial neoplasia (CIN) recurred in 40 women after LEEP.

In a logistic regression analysis, factors independently associated with recurrence were:

- Glandular involvement (OR 9.11; 95% CI 3.02-27.48);
- HIV infection (OR 4.6; 95% CI 1.88-11.21);
- Compromised margins of cervical lesions (OR 2.59; 95% CI 1.07-6.7).

Rates of recurrence were 33% among HIV positive women, compared with 8% among HIV negative women, a significant difference (P < 0.05).

Among the women with HIV, risk of recurrence was higher among those with lower CD4 cell counts.

In a multivariate analysis, recurrence was most common among women with both glandular involvement and compromised margins.

No cases of CIN progressed to invasive cervical cancer.

Conclusion

The researchers concluded that the "[m]ain risk factors associated [with] cervical intraepithelial neoplasia recurrence after loop electrosurgical excision procedure were HIV-1-infection, glandular involvement, and compromised margins in cone biopsy."

Need for Screening and Treatment

In wealthy countries, invasive cervical cancer is not more common among HIV positive women, largely due to routine Pap screening that detects early cervical lesions at a treatable stage. In low-income countries before the advent of HAART, women with cervical abnormalities typically died of other causes before they had a chance to develop full-blown cervical cancer. In the Brazilian study, the absence of progression to invasive cancer may have been attributable to regular follow-up care.

The authors of the Zambian study concluded, "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."

8/21/06

References

G Parham, V Sahasrabuddhe, S Vermund, and others. Prevalence and predictors of squamous intraepithelial lesions of the cervix in HIV-infected women in Lusaka, Zambia. XVI International AIDS Conference. Toronto, August 13-18, 2006. Abstract TUAB0303.

G Parham, V V Sahasrabuddhe, M H Mwanahamuntu, and others. Prevalence and predictors of squamous intraepithelial lesions of the cervix in HIV-infected women in Lusaka, Zambia. Gynecologic Oncology. July 26, 2006 [Epub ahead of print].

M I M Lima, V H Melo, C P Tafuri, and others. Risk factors to cervical intraepithelial neoplasia recurrence after loop electrosurgical excision procedure in HIV-1- infected and non-infected women. XVI International AIDS Conference. Toronto, August 13-18, 2006. Abstract TUAB0304.


 

 

 

 

 

 

 

 





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