High prevalence and incidence of pre-cancerous cervical lesions in HIV-positive South African women

There is a high prevalence and incidence of pre-cancerous cervical lesions in HIV-positive South African women, investigators report in the online edition of AIDS.

“This is the most comprehensive longitudinal report of cytological progression and regression of a large number of HIV-infected women followed prospectively in a high HIV, high HPV [human papillomavirus] setting,” comment the researchers.

They add, “over one-quarter of women with a baseline normal or [low grade] lesions progressed to high grade cervical lesions during follow-up.”

Antiretroviral treatment had a moderately protective effect against progression of lesions.

The authors believe that their findings have implications for cervical screening strategies in South Africa. However, they do not think that annual check-ups would be cost effective. Instead, they recommend that the frequency of screening should be determined by CD4 cell count.

Access to HIV therapy in South Africa is increasing, therefore significantly extending the prognosis of a large proportion of patients. Infection-related malignancies, such as cervical cancer, are an increasingly important cause of illness and death in patients with HIV.

Treatment for cervical cancer is more likely to succeed if pre-cancerous cell changes are detected early. Therefore investigators wished to establish the prevalence and progression of cervical lesions among HIV-positive women in Soweto.

A total of 2325 women had a cervical smear between 2003 and 2009. Only 4% were taking HIV treatment at baseline, but a further 15% initiated therapy during follow-up.  The women were followed for a median of 24 months.

At the time of the initial screen, 38% of women had pre-cancerous lesions. Their average age was 32 and their median CD4 cell count 254 cells/mm³, which was significantly lower than the median of 351 cells/mm³ observed in women with normal cervical cytology (p < 0.0001).

Each 100 cell/mm³ increase in CD4 cell count reduced the risk of low-grade lesions by 13%, and high-grade lesions by 18%.

In addition, each five year reduction in age reduced the risk of low-grade lesions was 10%.

A subsequent smear was performed on 1193 women. Women who had only one smear were significantly more likely to have abnormal lesions at baseline (p < 0.001). They were also more likely to have been lost to follow-up or to have died (p < 0.001).

Overall, 11% of women with a normal cytology or low-grade lesions at baseline developed high-grade lesions. This provided an incidence of 9.6 per 100 person years.

Of the 832 women whose first smear results were normal, 22% developed low-grade lesions and 1% high-grade lesions.

However, an improvement in cervical cytology was also observed in many women.

When the investigators looked at the smear results of the 225 women with low grade lesions at baseline, and who had a second smear at least 11.5 months later, they found that the lesions had regressed in 44% of individuals.

Patients with a CD4 cell count  below 200 cells/mm³ were almost twice as likely as those with a CD4 cell count above 500 cells/mm³ to experience disease progression (p < 0.0001).

Taking HIV treatment reduced the risk of disease progression by 28%. (p < 0.05). “We were able to show a protective effect of HAART [highly active antiretroviral therapy] despite short durations of ART,” write the authors.

Only age above 45 was associated with the regression of lesions. This finding surprised the investigators, who commented: “low grade lesions in older women would be expected to be more persistent lesions. The protective effect of age…is unexplained.”

The researchers believe that their findings have implications for cervical screening programmes in South Africa. It is current practice to screen women every ten years, but the authors recommend “shorter screening intervals” for women with a CD4 cell count below 500 cells/mm³.

However, they do not believe that annual screening would be an efficient use of scare healthcare resources, as many abnormalities are “transient” and destined to “resolve with time”.

Instead they believe that the screening interval should be determined by a patient’s CD4 cell count, and that patients with weak immune systems should have the most frequent monitoring.