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CDC HIV/AIDS/Viral Hepatitis/STD/TB Prevention News Update
Increased Risk of High-Grade Cervical Squamous Intraepithelial
Stephen E. Hawes; Cathy W. Critchlow; Mame A. Faye Niang;
October 23, 2003
Journal of Infectious Diseases (08.03) Vol. 188; No. 4: P.555-

The authors studied 4,119 women attending an outpatient clinic in Senegal to assess the risk of prevalent high-grade cervical squamous intraepithelial lesions (HSILs) or invasive cervical cancer (ICC) associated with HIV-1, HIV-2, HPV infections, HIV load and CD4 cell count. They hypothesized that, among HIV- positive women, those with severe immunosuppression would be at greatest risk of prevalent HSILs or ICC. Since a slower CD4 cell decline characterizes HIV-2, the researchers further hypothesized that the longer periods of immunosuppression characteristic of HIV-2 infection would result, after adjusting for CD4 cell count, in an increased risk for HSILs or ICC among HIV-2-positive women compared to HIV-1-positive women.

The investigators found that 433 (10.5 percent) of the 4,119 women were HIV-positive. Among that group, 335 (8.1 percent) had HIV-1 only, 69 (1.7 percent) had HIV-2 only, and 29 (0.7 percent) were dually infected with HIV-1 and HIV-2. "HIV- positive women were older, more likely to work as a commercial sex worker (CSW) and less likely to have received any formal education or use contraception than were HIV-negative women. HIV-2-positive women were somewhat older than HIV-1 positive women," according to the study. Women infected with HIV-2 only had higher CD4 cell counts than women with HIV-1 only. Women with dual infection had levels "intermediate to those of women with single HIV infection," the researchers noted.

"HIV infection was associated with increased rates of cervical infection with high-risk HPVs," the investigators found. Among women with high-risk HPVs, those with HIV-1, HIV-2 or dual infection were more likely than HIV-negative women to have HSILs or ICC. The association was not found among women who did not have high-risk HPVs. In HIV-positive women, higher HIV plasma RNA loads and lower CD4 cell counts were associated with high-risk HPV infection and degree of cervical abnormality. HIV-2-positive women were more likely to have HSILs than HIV-1-positive women.

"We and other researchers hypothesize that the increased risk of HPV-related neoplasia due to HIV infection results from HIV-induced immunosuppression and the loss of the ability to control HPV expression," the report stated. "In most women, HPV infections, even with high-risk types of HPV, are self- limited, with few long-term consequences. However, in individuals unable to control HPV infection (i.e., women with HIV-induced immunosuppression), persistent HPV expression allows prolonged exposure to HPV oncoproteins E6 and E7, which interfere with the host's normal cell-cycle controls and lead to the accumulation of populations of genetically abnormal cells. In the present study, we found cervical infection with high-risk ('oncogenic') HPV types to be common in African women, with HPV detected in 52 percent and 15 percent of women with and without HIV, respectively." "Results from ongoing cohort studies of HIV-negative women and women with HIV-1 and/or HIV-2 infection will be useful in clarifying temporal relationships between progression of HIV- induced immunosuppression and detection and load of high-risk HPV types in the development of high grade cervical lesions, including ICC," the authors concluded.

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