Women with HIV who have undergone hysterectomy often have abnormal Pap smears indicating vaginal intraepithelial neoplasia (pre-cancerous cell changes), according to an American study published in the April 15th edition of the Journal of Acquired Immune Deficiency Syndromes.
Past research has shown that about one-third of women with HIV have abnormal cervical cell changes. HIV-infected women are also at higher risk for cervical intraepithelial neoplasia (CIN), although one recent study indicated that they have a low rate of invasive cervical cancer (see link to news story below). This study looked at whether women who had undergone hysterectomy (surgical removal of the uterus) had abnormal vaginal cytology.
The present research examined data from the HIV Epidemiology Research (HER) Study, a prospective multi-site study of HIV-infected and at-risk uninfected women. In total, the study enrolled 871 HIV-positive and 439 HIV-negative women in four US cities. This analysis included 102 HIV-positive and 46 HIV-negative women who had a hysterectomy either before or during the study. Women received Pap smears during each semi-annual visit; and those with abnormal cell changes also received colposcopies. In addition, all women were tested for the presence of human papilloma virus (HPV).
A Pap smear involves examination of a sample of cells under a microscope. If abnormal cell changes are detected, the test is typically followed by a colposcopy, in which a lighted microscope is used to examine the cervix or vagina. If there is still evidence of abnormality, a biopsy sample is usually obtained. Although different classification systems are used, abnormal cells are generally categorized as atypical squamous cells (ASCUS); low-grade squamous intraepithelial lesion (SIL), intraepithelial neoplasia grade I, or mild dysplasia; high-grade SIL, intraepithelial neoplasia grade II/III, moderate-to-severe dysplasia, or carcinoma in situ (CIS); or invasive cancer. HPV is known to cause abnormal cell growth, including genital warts; some types, including 16, 18, 31, and 45, are associated with cancer.
Baseline characteristics of the HIV-infected and uninfected women in this study were generally similar, although the women with HIV were more ethnically diverse. The mean age was about 40, and about two-thirds had given birth to at least two children. More HIV-infected women smoked tobacco and used condoms, but fewer had had two or more male sex partners during the previous six months. Smoking and multiple sex partners are risk factors for cervical cancer, while condom use appears protective.
Twenty-six HIV-infected and 11 uninfected women had hysterectomies during the study period. CIN was the most common indication for hysterectomy among the HIV-infected women, present in 19 (73%). Among the uninfected women, only one (9%) had CIN; most (73%) had uterine fibroids. CIN rates were not available for women who had had a hysterectomy prior to the start of the study.
Among the 76 HIV-infected women who had undergone hysterectomies prior to the study, 33 (43%) had low-grade vaginal SIL and 17 (22%) had atypical squamous cells as their highest grade Pap smear result; 26 (34%) had consistently normal smears and none had high-grade SIL. Among the 26 HIV-infected women who had hysterectomies during the study, three (12%) had high-grade SIL, nine (35%) had low-grade SIL, and two (8%) had atypical squamous cells; 12 (46%) had consistently normal results. Twelve (63%) of the 19 women who had CIN before hysterectomy had high-grade or low-grade SIL during follow-up, compared with none of the seven without previous CIN (p
None of the HIV-uninfected women had evidence of either high-grade or low-grade vaginal SIL during the study. Two (18%) of the 11 who had hysterectomies during the study and 11 (31%) of the 35 who had the surgery prior to the study had atypical squamous cells; the rest had consistently normal results. Among the women who underwent hysterectomy during the study, the rate of vaginal SIL was 11 per 100 person-years for the HIV-positive women, compared with 0 per 100 person-years for the HIV-negative women (p
Biopsy samples were available for 18 HIV-infected women. Among those with vaginal SIL, six showed evidence of grade I vaginal intraepithelial neoplasia (VAIN), three showed grade II VAIN, and four showed grade III VAIN. One woman with atypical squamous cells and two with normal Pap results showed evidence of grade I VAIN. In total, 16 (16%) of the 102 HIV-positive women had biopsies showing VAIN. None of the 46 HIV-negative women had abnormal colposcopy results that suggested the need for a biopsy.
Among the HIV-positive women, those with a CD4 cell count of less than 200 and/or an HIV viral load greater than 10,000 copies/ml at the time of hysterectomy were more likely to have vaginal SIL. In a multivariate analysis, lower CD4 count, infection with oncogenic (cancer-causing) HPV strains, genital warts, and less education were associated with a higher risk for SIL. Surprisingly, current use of HAART was also correlated with increased SIL risk. In contrast, several previous studies have found that effective antiretroviral therapy reduced the chances of cervical neoplasia, while others found no effect.
The frequency of abnormal cytology and biopsy results in the HIV-positive women in this study was substantially higher than that seen in women in the general population. For example, in one study of 810 women with high-grade SIL who underwent hysterectomy, only 13 (2%) had recurrent SIL after surgery. In another study of 219 women with high-grade SIL at the time of hysterectomy, eight (4%) later had abnormal vaginal Pap results and only two (1%) developed VAIN. In one previous study of HIV-positive women without hysterectomies, just 1% had intraepithelial neoplasia of the anogenital area.
Because the rate of VAIN in the general population is low, most women receive only routine cervical - not vaginal - Pap smears. However, the American Cancer Society recommends that women should receive vaginal Pap tests after a hysterectomy if they had moderate-to-severe neoplasia or cervical cancer prior to surgery. The American College of Obstetrics and Gynecology recommends post-hysterectomy vaginal cytology screening for women with HIV or other risk factors.
“The high rate of SIL on vaginal Papanicolaou smears and the presence of high-grade vaginal intraepithelial neoplasia among HIV-infected women after hysterectomy demonstrate the need for continued follow-up for lower genital tract lesions,” the researchers concluded.
Further information on this website
Invasive cervical cancer risk no higher in women with HIV - news story
Paramsothy P et al. Abnormal vaginal cytology in HIV-infected and at-risk women after hysterectomy. Journal of Acquired Immune Deficiency Syndromes 35: 484–491, 2004.