HIV-positive women are four times more likely to have abnormal cervical cells than HIV-negative women, according to a US study involving over 1,000 patients published in the July 1st 2003 edition of the Journal of Infectious Diseases.
The study also found that in HIV-positive women with a CD4 cell count below 500 cells/mm3 and with human papilloma virus (HPV) infection, abnormal cervical cells are much more likely to be pre-cancerous, and that treatment with HAART was does not promote disease regression.
Cervical squamous intraepithelial lesions (SILs) are the most common gynaecological symptom of HIV-infection. HPV infection has been shown to increase the risk of SILs. People with immunosuppression caused by HIV, appear to be more vulnerable to HPV infection, the reactivation of HPV, and the inability of the immune system to clear the infection, leading to increased risk of cervical dysplasia and cancer.
Investigators involved in the US HIV Epidemiology Research Study (HERS), a multicentre, longitudinal study wished to establish the incidence of SILs in HIV-positive women, and to compare it to that seen in a control population of HIV-negative women at high risk of HIV infection. The investigators also wished to see how SILs progressed in both HIV-positive and HIV-negative women and establish factors involved in either the progression or regression of lesions.
Data from 774 HIV-positive women and 391 HIV-negative women were analysed in the course of the study. The women were aged between 16-65 and had comparable demographic backgrounds. Follow-up was for an average of four years between 1993 and 1999. At baseline, 134 HIV-positive and 18 HIV-negative women had Pap smears which suggested SILs. By the time of the first follow-up visit 145 (19%) of HIV-positive women and 18 (5%) of HIV-negative women had SILs.
By the end of the study, 224 (35%) of HIV-positive women and 34 (9%) of HIV-negative women had had a Pap test indicating SILs. The incidence rate of SILs in HIV-positive women was 11.5 cases per 100 patient years compared to 2.6 cases per 100 patient years in the HIV-negative women.
High-grade lesions developed in 47 (7%) of HIV-positive women during follow-up compared to four (1%) of HIV-negative women.
Risk factors for SILs in HIV-positive women were CD4 cell count of below 500 cells/mm3, and HPV infection. HIV viral load was not found to be significantly associated with the risk of SILs. Investigators also found that treatment with HAART did not appear to have a protective effect against the development of SILs.
Progression of SILs to high-grade lesions was associated with a CD4 cell count below 200 cells/mm3 (2.17, 95% CI, 1.44-3.28, p<.001 a="" and="" between="" cd4="" cell="" cells="" count="" extent="" lesser="" to="">3 (1.63, 95% CI, 1.11 – 2.39, p=.013).
Infection with strains of HPV also increased the likelihood of SILs progressing to high-grade lesions. Unsurprisingly, HPV strains associated with an increased risk of high-grade lesions had the highest risk ratio of progression (21.48, 95% CI, 12.95 – 35.64, p<.001 an="" chances="" haart="" had="" hiv="" impact="" load="" neither="" nor="" of="" on="" progression.="" the="" treatment="" viral="" with="">
HIV-positive women with a CD4 cell count below 500 cells/mm3 (CD4 cell count below 200 cells/mm3 0.97 95% CI, 0.55-1.70, p=.91; CD4 cell counts 200 – 500 cells/mm3 0.89 95% CI, 0.54 – 1.47, p=.65) were less likely to experience an improvement in SILs. In addition, investigators found that the chances of regression decreased with every log increase in HIV viral load (0.78 95% CI, 0.65 – 0.94, p=.009). Women who received treatment with HAART (0.86 95% CI, 0.50 – 1.47, p=.57) were no more likely to experience regression than those who received either sub-optimal antiretroviral therapy (0.95 95% CI, 0.67 – 1.36, p=.78) or no anti-HIV treatments.
The investigators conclude that HIV-positive women “had higher risk of cervical SILs, including high-grade SILs, than did HIV-negative women, with more than one-third of HIV-seropositive participants developing SILs during follow-up.”
They also suggest that HPV may increase the risk of SILs in HIV-positive women by interacting with HIV infection at a molecular level.
The investigators also note that HAART was not associated with a decreased risk of SILs or with regression. However, they emphasise the observational nature of their study “which was not ideal for evaluating the impact of HAART on the natural history of cervical dysplasia.”
The study ends with a call for the development of “innovative and cost effective methods of screening for and treating SILs in the growing numbers of HIV-infected women living longer lives.”
Further information on this website
Human papilloma virus - overview
Genital warts - factsheet
Schuman P et al. Longitudinal study of cervical squamous intraepithelial lesions in human immunodeficiency virus (HIV)-seropositive and at-risk HIV-seronegative women. Journal of Infectious Diseases 188, on-line edition, 2003.