Natural History of Low-Grade Squamous Intraepithelial Lesions in Women Infected with Human Immunodeficiency Virus (1996)

To the Editor: Recent literature has established that women infected with the human immunodeficiency virus (HIV) are at higher risk for squamous intraepithelial lesions (SIL) when compared to noninfected women (1,2). Several studies have also reported that cervical disease in HIV-infected women is more likely to present with advanced grades and to progress, persist, or reoccur after therapy (3-5). Optimal management of low-grade SIL of the cervix in HIV-infected women is controversial. Because of the potentially more virulent course of SIL in HIV-infected women, it is unclear whether women having low-grade SIL should undergo early therapy vs. periodic colposcopic follow-up. To describe the natural history of cytologically diagnosed low-grade SIL in a cohort of HIV-infected women who did not receive therapy for low-grade lesions, we conducted a retrospective chart review of all women without a history of high-grade SIL who were diagnosed with low-grade SIL cytologically after enrollment into the HIV Outpatient Program (HOP) clinic based at the Medical Center of Louisiana in New Orleans. HOP clinic charts are abstracted retrospectively semiannually and data are entered into a local data base, established November 1990. Women ever having an abnormal cervical study were identified through this local data base and included in this study if they had (a) more than one papanicolaou (Pap) smear after HOP entry, (b) low-grade SIL identified on at least one Pap smear, (c) no history of high-grade SIL prior to HOP entry, and (d) no history of ablative or surgical treatment for SIL prior to HOP entry. Pairwise mean differences in CD4 cell counts between subgroups of women were tested in t test analyses. Of 274 adolescent and adult women enrolled into HOP between April 1989 and October 1994, 132 (48%) had at least one abnormal cervical smear. Sixty-four women were excluded from this study for the following reasons: (a) only one Pap smear was performed in HOP (n = 9), (b) only nonspecific findings (defined as atypia, reactive and reparative changes, and HPV effects without SIL) were noted on Pap smears (n = 32), and (c) a history of high-grade SIL or ablative/surgical treatment (n = 22). Analyses of the remaining 69 women included in the study showed that 96% of the cohort was African American and 33% had a history of injection drug use (IDU). Median age and CD4 cell count at HOP entry were 23 years (range 14-57 years) and 374/mm3 (range 4-1, 165/mm3), respectively. The median number of Pap smears performed in the HOP clinic was five (range two to 11) and median time of follow-up per participant was 20 months (range 6-61 months). Six women had biopsy confirmed low-grade SIL. The remaining 63 women had only a cytologic diagnosis of low-grade SIL. Cervical studies (Pap smear or cervical biopsy) subsequent to the diagnosis of low-grade SIL showed the following: nine women high-grade SIL (median progression time 14 months), 36 women nonspecific findings (median regression time 12 months), and 42 women normal findings (median regression time 11 months). Forty-three (72%) of the 60 women who had no progression on cervical studies had regression to nonspecific or normal findings. Three of the nine women who appeared to progress from low- to high-grade SIL had repeat Pap smears (n = 2) or a cervical biopsy (n = 1) which showed either low- grade SIL or nonspecific or normal findings. Three women without biopsy confirmed high-grade SIL and noncompliant with clinic visits had not had a follow-up colposcopy. The remaining three women had biopsy confirmed high-grade SIL. Although not significant, the mean CD4 cell count of women who progressed to high-grade SIL vs. that of nonprogressors was lower (382 vs. 452/mm3) and the mean CD4 cell count of women who regressed to atypical or normal findings vs. that of nonregressors was higher (482 vs. 370/mm3). This study was limited by the retrospective design and infrequent performance of cervical biopsies to confirm the cytologic diagnosis of low-grade SIL. Wright et al. (2) determined the sensitivity and specificity of Pap smears in HIV-infected women to be 81% and 87%, respectively, and it is probable that some women may have had a misclassified SIL status or grade. The cohort of women in this study differed demographically from previously described cohorts. Women enrolled into HOP were generally younger and predominantly African American. Generalization of findings from this study to other populations of HIV-infected women may therefore not be valid. Regardless of these limitations, the natural history of SIL in the HOP cohort suggests that cytologically diagnosed low-grade SIL does not inevitably progress rapidly in HIV-infected women and, in fact, often regresses. Not surprisingly, progressors appear to have a lower mean CD4 cell count than nonprogressors. Prospective studies to better delineate risks for SIL progression are warranted to optimally manage cervical dysplasia in the HIV-infected population. Peter Belafsky Tulane School of Public Health and Tropical Medicine Rebecca A. Clark; Patricia Kissinger; Jose Torres Louisiana State University Medical Center; New Orleans, Louisiana, U.S.A.