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Background: Women infected with human immunodeficiency virus (HIV) have an increased risk of persistent squamous intraepithelial lesions (SILs) of the cervix. We assessed the association between use of highly active antiretroviral therapy (HAART) and regression of SIL in HIV-infected women enrolled in the Women's Interagency HIV Study, a large, multicenter, prospective cohort study., Methods: Of 2059 HIV-infected participants, 312 HIV-infected women had normal cervical cytology at baseline and were subsequently diagnosed during 7 years of follow-up with incident SIL. Pap smears, CD4+ T-cell counts, and information regarding use of HAART were obtained every 6 months. The outcome of interest was lesion regression, defined as two consecutive normal Pap smears 6 months apart. Incidence rates of SIL regression were computed among person-years at risk, both before and after HAART initiation. All statistical tests were two-sided., Results: Of 312 women, 141 had lesions that regressed to normal cytology, with a median time to regression of 2.7 years. Overall, the incidence of regression increased (P(trend) =.002) over time after HAART was introduced. At incident SIL, median CD4+ T-cell counts were lower in women whose lesions did not regress than in women whose lesions regressed (230 versus 336 cells/microL; P<.01). Before HAART was introduced, the rate of lesion regression was 0.0% (95% confidence interval [CI' = 0.0% to 2.4%). After HAART was introduced, the rate was 12.5% (95% CI = 9.9% to 15.1%) and was related to post-HAART CD4+ T-cell counts (P(trend) =.002)., Conclusions: HAART use was associated with increased regression of SIL among HIV-infected women, and among women who used HAART, increased CD4+ T-cell counts were associated with a greater likelihood of regression. However, the majority of cervical lesions among HIV-infected women, even among individuals who used HAART, did not regress to normal.

Purpose: To assess the utility of testing for high-risk human papillomavirus (HPV) DNA as a triage strategy for detecting cervical intraepithelial neoplasia (CIN) grade 2/3 in women with human immunodeficiency virus-1 (HIV-1) infection and cytology read as atypical cells of uncertain significance (ASCUS)., Methods: Conventional cervical cytology and cervicovaginal lavage were obtained at 6-month intervals between October 1, 1994, and September 30, 2002, from women enrolled in the Women's Interagency HIV Study, a multicenter cohort studying the natural history of HIV in women. HPV typing was performed by PCR. HPV types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68 were classified as carrying high oncogenic risk. Women with ASCUS smears were referred for colposcopy. Analyses of the sensitivity of HPV testing were cross-sectional, using colposcopy results within 90 days of first ASCUS result., Results: Of the 270 women evaluated, 7 (3%) had CIN 2, and 3 (1%) had CIN3 or adenocarcinoma in situ. High-risk HPV DNA was found in 81 (30%) of the 270 participants. The sensitivity of high-risk HPV DNA detection for CIN 2/3 was 50% (95% CI 0.19, 0.81), the specificity was 71% (95% CI 0.65, 0.76), the positive predictive value was 6% (95% CI 0.01, 0.11), and the negative predictive value was 97% (95% CI 0.95, 1.00). HPV of any risk type was found in 176 (65%) of the 270 women, including 9 of 10 women with CIN 2/3, for a sensitivity of 90% (95% CI 0.56, 1.00), a specificity of 36% (95% CI 0.30, 0.42), a positive predictive value of 5% (95% CI 0.02, 0.08), and a negative predictive value of 99% (95% CI 0.94, 1.00)., Conclusions: For women with HIV and Papanicolaou smears read as ASCUS, DNA testing for high risk HPV may not be sensitive enough for clinical use.

Objective: To determine frequency and outcomes of pregnancy in US women with HIV before and after introduction of highly active antiretroviral therapy (HAART)., Design: Prospective cohort study at six US centers., Methods: HIV seropositive and at-risk seronegative women reported pregnancy outcomes at 6-month intervals during the period 1 October 1994 to 31 March 2002. Outcomes were tabulated and pregnancy rates calculated. Logistic regression defined outcome correlates., Results: Pregnancy rates were 7.4 and 15.2 per 100 person-years in seropositive and seronegative women, respectively (P < 0.0001). Among seropositives, 119 (36%) pregnancies ended in live birth, six (2%) in stillbirth, 126 (36%) in abortion, 83 (24%) in miscarriage, 16 (5%) in ectopic pregnancy, and two (1%) in other outcomes (P = nonsignificant versus seronegatives). Independent baseline correlates of conception in seropositives included younger age [odds ratio (OR), 1.20; 95% confidence interval (CI), 1.16-1.23], prior abortion (OR, 1.79; 95% CI, 1.25-2.63), lower HIV RNA levels (OR, 1.30; 95% CI, 1.10-1.54 for each log decrease), and being unmarried (OR, 1.59; 95% CI, 1.02-2.44). Baseline antiretroviral use at baseline was linked to lower conception risk (OR, 0.34; 95% CI, 0.49-0.98 for mono- or combination therapy; OR, 0.34; 95% CI, 0.03-4.28 for HAART). Abortion was less likely during the HAART era, (OR, 0.68; 95% CI, 0.35-1.33 during the early HAART era; OR, 0.46; 95% CI, 0.23-0.90 during the later HAART era, compared with before HAART)., Conclusions: Women with HIV were less likely to conceive than at-risk uninfected women, but pregnancy outcomes were similar. Abortion became less common after the introduction of HAART.

Objective: To measure the incidence of invasive cervical cancer (ICC) in US women infected with HIV., Design: Multicenter prospective cohort study, conducted between October 1994, and September 2001., Setting: HIV research centers operating as six urban consortia in the Women's Interagency HIV Study., Subjects: A total of 2131 women (462 HIV seronegative, 1661 HIV seropositive, and eight seroconverters). Women with a history of hysterectomy or of cervical cancer at baseline evaluation were excluded., Intervention: Cervical cytology obtained at 6-month intervals, with a colposcopy referral threshold of atypia, followed by individualized treatment., Main Outcome Measure: ICC diagnoses obtained from study databases and regional cancer registries and confirmed by a gynecologic pathologist., Results: No incident ICC were observed in HIV seronegative women during 2375 woman-years of observation. During 8260 woman-years of observation, eight putative incident cases of cervical cancer were identified in HIV seropositive women, but only one was confirmed, yielding an incidence rate of 1.2/10 000 woman-years (95% confidence interval, 0.3-6.7/10 000 woman-years). The difference in incidence between HIV seropositive and seronegative women was not significant (P = 1.0)., Conclusion: ICC is uncommon in HIV-infected US women participating in a regular prevention program.

Serum samples from 2008 human immunodeficiency virus (HIV)-positive and 551 HIV-negative women were tested for immunoglobulin A (IgA) to human papillomavirus (HPV) type 16 capsids. IgA seropositivity was lower than previously reported IgG seropositivity (7% vs. 51%), but, like IgG antibodies, HPV 16 IgA was associated with sexual behavior, cervicovaginal HPV 16 DNA, and cytological abnormalities. IgA seropositivity was higher in HIV-positive women than in HIV-negative women (7.7% vs. 4.9%; P=.02), but the association was lost after adjustment for HPV 16 cervicovaginal infection. IgA, but not IgG, seropositivity was associated with progression to high-grade cytological abnormalities (relative hazard [RH], 2.2 [95% confidence interval, 1.2-4.2]), raising the possibility that an IgA response to HPV 16, as described for other DNA viruses, may be a marker of persistent viral replication. The risk of incident infection with non-16-related HPV types was increased in IgA seropositive women (RH, 1.8 [95% confidence interval, 1.3-2.6]), compared with seronegative women (RH, 2.2 [95% confidence interval, 0.9-5.4]), but there was no difference in the risk of incident HPV 16 or HPV 16-related infections. This may be evidence of partial type-specific or clade-specific immunity conferred by seropositivity to HPV 16 capsids.

Background: Human papillomavirus (HPV) type 16 is etiologically associated with approximately half of all cervical cancers. It is important, therefore, to determine the characteristics that distinguish HPV16 from other HPV types. A preliminary result based on cross-sectional baseline data in the Women's Interagency Human Immunodeficiency Virus (HIV) Study (WIHS) suggested that the prevalence of HPV16 might have a weaker association with immune status in HIV-seropositive women than that of other HPV types. To address this issue, we examined HPV test results from repeated study visits in the WIHS and from an independent study, the HIV Epidemiology Research Study (HERS)., Methods: HIV-seropositive women in the WIHS (n = 2058) and in the HERS (n = 871) were assessed semiannually. HPV DNA was detected in cervicovaginal lavage specimens by using polymerase chain reaction assays. Prevalence ratios were used to compare the prevalence of each HPV type in women with the lowest CD4+ T-cell counts (<200 T cells/mm3) with that of women with the highest CD4+ T-cell counts (> or =500 T cells/mm3). A summary prevalence ratio for each HPV type (i.e., across visits and studies) was estimated using generalized estimating equations. The association of CD4+ T-cell stratum with type-specific HPV incidence was measured using multivariable Cox regression models. All statistical tests were two-sided., Results: The prevalence ratio for HPV16 was low compared with that of other HPV types at every study visit in both cohorts. The generalized estimating equation summary prevalence ratio for HPV16 (1.25, 95% confidence interval [CI] = 0.97 to 1.62) was the smallest measured, and it was statistically significantly lower than that of all other HPV types combined (P =.01). The association of CD4+ T-cell stratum with HPV16 incidence was also among the smallest measured (hazard ratio = 1.69, 95% CI = 1.01 to 2.81)., Conclusions: The prevalent and incident detection of HPV16 is more weakly associated with immune status in HIV-seropositive women than that of other HPV types, suggesting that HPV16 may be better at avoiding the effects of immune surveillance, which could contribute to HPV16's strong association with cervical cancer.

Objective: The study was undertaken to provide consensus guidelines for the management of women with histologically confirmed cervical intraepithelial neoplasia (CIN) that can act as a precursor to invasive cervical cancer and represents one of the most common significant gynecologic diseases of women of reproductive age., Participants: An independent panel of 121 experts in various aspects of the diagnosis and management of cervical cancer precursors, including representatives from 29 participating professional organizations, federal agencies, national and international health organizations, and others were invited by the American Society for Colposcopy and Cervical Pathology (ASCCP)., Consensus Process: Guidelines for the management of women with CIN were developed through a multistep process. Draft management guidelines were developed by working groups who performed formal literature reviews and obtained input from the professional community at large by way of an interactive internet-based bulletin board. At the ASCCP Consensus Conference, September 6 through 8, 2001, in Bethesda, Md, all guidelines were discussed, revised, and adopted by formal vote., Conclusion: Evidence-based guidelines have been developed for the management of women with biopsy-confirmed CIN.

Objective: The aim of this study was to determine the strength of the correlation between colposcopic impression and biopsy histology., Methods: In an urban referral clinic, colposcopy and directed biopsy were performed between July 1, 1996, and December 31, 1999, by residents supervised by board-certified attending obstetrician-gynecologists. Impression and biopsy were graded as benign, suggesting condyloma or koilocytosis, cervical intraepithelial neoplasia (CIN) grades 1-3, or cancer. The significance of association was assessed by chi(2) testing and the strength by kappa statistics., Results: Colposcopies were performed on 2825 women, with colposcopic impression and biopsy grade known for 2112. Exact agreement was found in only 893 (37%) women, but results agreed within one grade in 1203 (75%). The association between impression and histology was significant (P < 0.001), but the strength of the correlation was poor (0.20). The positive predictive value of any colposcopic abnormality for any histologic abnormality was 80%. The negative predictive value of a benign colposcopic impression was 68%. The sensitivity of colposcopy with a threshold of any lesion detected was 89%, and the specificity was 52%. The sensitivity for CIN 2/3 was 56%., Conclusion: Colposcopy is imprecise, although useful in estimating lesion grade. Management decisions require biopsy.

Objective: The aim of this study was to determine rates of cervical neoplasia among women at least 50 years of age referred for colposcopy after abnormal cytology and to compare these to younger women., Methods: From a prospectively accrued database of 2825 women undergoing colposcopy in the gynecology clinic of an urban public hospital, women at least 50 years of age with a known cytologic abnormality were selected for retrospective analysis. Demographic and medical information collected at colposcopy and subsequent histology was reviewed. Cytology results were based on the Bethesda system, and histology was reported as grades of cervical intraepithelial neoplasia (CIN). Statistical analysis was by t test, chi(2) test, and Mann-Whitney U test., Results: Among 325 women at least age 50, cervical histologic results were benign or atypical for 147 (45%), CIN1 for 28 (9%), CIN2 for 21 (6%), CIN3 for 49 (15%), cancer for 11 (3%), and ungraded dysplasia for 7 (2%), with no biopsy performed for 62 (19%) women. Symptoms were more common among women with cancer (6/11 or 55%) than those without (62/263 or 21%, P = 0.01). Negative histology (80/231 or 35%), CIN3 (49/231 or 21%), and cancer (9/231 or 4%) were more common among older than younger women (287/1403 or 20%, 199/1403 or 14%, and 11/1403 or 1%, respectively), while atypia (438/1403 or 31%), CIN1 (321/1403 or 23%), and CIN2 (147/1403 or 10%) were more common among younger than older women (53/231 or 23%, 23/231 or 10%, and 17/231 or 7%, respectively, P < 0.04). Differences in the distribution of cervical histology results remained significant among women with ASCUS (P = 0.001) but not those with LSIL (P > 0.9), HSIL (P > 0.07), or cancer (P > 0.4)., Conclusions: Most older women are referred for colposcopy with lesser grades of abnormality, but cervical cancers are found across all cytologic grades and were more common in symptomatic women. Compared to younger women with abnormal cytology, women at least 50 years of age with ASCUS had higher rates of negative evaluations and high grade but not low- or mid-grade lesions.

Baseline serum samples from 2815 human immunodeficiency virus (HIV)-positive and 963 HIV-negative women enrolled in 2 cohort studies were tested for immunoglobulin G antibodies to human papillomavirus type 16 (HPV-16) capsids. HPV-16 seropositivity was associated with lifetime number of sex partners (P<.001) among both HIV-positive and HIV-negative women. Approximately 50%-60% of HPV-16 DNA-positive women were HPV-16 positive. HPV-16 seropositivity was associated with HIV infection; however, after adjustment for baseline cervical HPV infection and disease, the association disappeared. Thus, the high seroprevalence of HPV-16 among HIV-positive women may be explained by a high prevalence of HPV of all types. Approximately 50% of HIV-positive women had serological evidence of prior HPV-16 infection, but only approximately 5% had an HPV-16 cervical infection at baseline. Despite the higher prevalence of HPV infection in this group, most HIV-positive women are able to control HPV-16 replication at the cervix, and reactivation, if it occurs, is not very common.

Objective: To enhance the yield of endocervical curettage (ECC) by defining risks for abnormality., Study Design: Demographic and medical information collected at colposcopy and subsequent histology were reviewed retrospectively. Statistical analysis was by t and chi 2 tests., Results: Among 2,287 women undergoing ECC at colposcopy, in only 105 (5%) did positive ECC require excisional therapy that would not otherwise have been recommended. Women with positive ECC were older (mean, 39.0 vs. 33.2 years; P < .001) and of higher parity (mean, 3.0 vs. 2.0 births; P < .001), with earlier first intercourse (at 16.6 vs. 17.2 years, P = .006), more unsatisfactory colposcopy (148 [27%] of 545 women with unsatisfactory colposcopy vs. 183 [12%] of 1,523 women with satisfactory colposcopy; P < .001) and more colposcopic impressions of cervical intraepithelial neoplasia (CIN) 2-3 (163 [51%] of 323 vs. 443 [25.6%] of 1,730 women with low grade or a negative impression; P < .001). The likelihood of missed CIN 2-3 was 0.4%, with no missed cancers among women with satisfactory colposcopy and either a normal colposcopic impression (1/254) or nulliparity (2/474)., Conclusion: ECC identifies otherwise-undetected preinvasive and invasive lesions but may be avoided in women with satisfactory colposcopy who are nulliparous or have no colposcopic lesions.

Objective: To provide evidence-based consensus guidelines for the management of women with cervical cytological abnormalities and cervical cancer precursors., Participants: A panel of 121 experts in the diagnosis and management of cervical cancer precursors, including representatives from 29 professional organizations, federal agencies, and national and international health organizations, were invited to participate in a consensus conference sponsored by the American Society for Colposcopy and Cervical Pathology (ASCCP)., Evidence and Consensus Process: Guidelines for the management of women with cervical cytological abnormalities were developed through a multistep process. Starting 6 months before the conference, working groups developed draft management guidelines based on formal literature reviews of English-language articles published in 1988-2001, as well as input from the professional community at large, obtained using interactive Internet-based bulletin boards. On September 6-8, 2001, the ASCCP Consensus Conference was held in Bethesda, Md. Guidelines with supporting evidence were presented and underwent discussion, revision, and voting., Conclusions: Management of women with atypical squamous cells (ASC) depends on whether the Papanicolaou test is subcategorized as of undetermined significance (ASC-US) or as cannot exclude high-grade squamous intraepithelial lesion (HSIL) (ASC-H). Women with ASC-US should be managed using a program of 2 repeat cytology tests, immediate colposcopy, or DNA testing for high-risk types of human papillomavirus (HPV). Testing for HPV DNA is the preferred approach when liquid-based cytology is used for screening. In most instances, women with ASC-H, low-grade squamous intraepithelial lesion, HSIL, and atypical glandular cells should be referred for immediate colposcopic evaluation.

Objective: To determine the risk of CIN3 and cancer in subsequent specimens among women with colposcopic biopsy showing CIN2., Methods: A retrospective review of demographic and medical information collected at colposcopy. Patient records were again reviewed 8 to 26 months later for information on procedures and histology results., Results: Histologic evaluation of specimens showed no lesions in 14, atypia or koilocytosis in 21, CIN1 in 25, CIN2 in 26, CIN 3 in 27, ungraded CIN in 3, and cancer in 3. No cancers were found in women at or below the median age of 33 years or those with satisfactory colposcopy. However, cancers were found in women with negative repeat cytology and negative colposcopic impression., Conclusion: Observation may be an option for young women with CIN2 on colposcopic biopsy if they are reliable for follow up and the entire squamocolumnar junction is seen.

Objective: Cervical intraepithelial neoplasia (CIN), a common condition among HIV-infected women, has been linked to HIV load and immune status. Highly active antiretroviral therapy (HAART) improves immunologic and virologic status. This study was undertaken to determine the relationship between HAART use and CIN., Design: Cohort study. The Women's Interagency HIV Study (WIHS) in five cities in the USA (Bronx/Manhattan, New York; Brooklyn, New York; Chicago, Illinois; Los Angeles, California; San Francisco Bay area, California; Washington, District of Columbia)., Methods: HIV-infected women were followed every 6 months with Papanicolaou smears and cervicovaginal lavage for human papillomavirus (HPV) DNA testing. To characterize exposures that changed over time and to capture the dynamic nature of cytologic changes, Papanicolaou smear findings from each participant's consecutive visits were defined as a pair. We determined the proportion of all pairs that exhibited either regression or progression, according to HAART exposure, HPV results and Papanicolaou smear status. As participants could contribute multiple pairs, inferences were based on robust methods to adjust for correlated observations., Results: Women with persistent HPV infection were more likely to have progression of their lesions. After adjustment for CD4 cell count and Papanicolaou smear status, women on HAART were 40% (95% confidence interval, 4-81%) more likely to demonstrate regression and less likely (odds ratio, 0.68; 95% confidence interval, 0.52-0.88) to demonstrate progression, Conclusions: HAART altered the course of HPV disease in HIV-infected women, reducing progression and increasing regression. As HPV disease is a common sex-specific manifestation of HIV disease this effect of HAART would be a major additional benefit from this modality of therapy.

Objective: To determine associations among cervical cytology, colposcopy, and biopsy in HIV-seropositive women., Materials and Methods: HIV-seropositive women and uninfected comparison women in a multicenter prospective cohort study underwent colposcopy for protocol indications. Women were eligible if they had a cervix, satisfactory cytology, and colposcopy between October 1994 and September 1999. Cytology, colposcopic impression, and biopsy were compared using equivalent categorizations. Kappa statistics with bootstrap sampling assessed strength of associations., Results: Colposcopy was performed in 978/1370 HIV-seropositive women and in 154/224 seronegative women. Biopsies were performed on 603 (44%) seropositive women at least once during 1015 colposcopy visits and on 82 (37%) seronegative women at 116 visits. The positive predictive value of cytology was 72% for seropositive women and 60% for seronegative women. The positive predictive value of colposcopy was 71% for seropositive women and 55% for seronegative women., Conclusion: The correlation between either cervical cytology or colposcopic impression and colposcopic biopsy was poor.

Objective: The goal of this study was to determine the colposcopic findings underlying cytologic abnormalities classified according to the Bethesda system., Methods: Women undergoing colposcopy for abnormal cytology at an urban teaching hospital between July 1, 1996 and December 31, 1999 had Papanicolaou smears repeated. Results were compared both with biopsy histology and with the worst histology reported after 8-26 months of follow-up. kappa statistics and Spearman's rho were calculated to determine the degree of agreement., Results: Colposcopy was performed for 2263 (94%) women. Referral and repeat Pap smears were reported identically in 493 (25%) of the 1962 women with results for both. No AGUS (atypical glandular cells of uncertain significance) smears were confirmed on repeat smear, and after excluding AGUS, agreement within one grade was found in 1305 of 1854 (70%). Among the 1842 women with squamous cytologic abnormalities, biopsy revealed a lesion more severe than that suggested by referral cytology in 577 (31%) and a less severe lesion in 648 (35%); exact correspondence was found in only 646 (35%). Of 317 women with ASCUS (atypical squamous cells of uncertain significance) on referral Pap smear, a negative repeat smear, and a specific biopsy result, 95 (30%) had true negative histology, while 148 (47%) had condyloma, 56 (18%) had cervical intraepithelial neoplasia (CIN) 1, 8 (3%) had CIN 2, 10 (3%) had CIN 3, and none had cancer. Comparison of repeat smear and colposcopic biopsy yielded a kappa statistic of 0.16., Conclusions: Cytology classified according to the Bethesda system does not accurately predict histologic diagnosis., (Copyright 2001 Academic Press.)

Objective: To determine incidence, progression, and regression rates for abnormal cervical cytology and their correlates among women with HIV., Methods: In a multicenter prospective cohort study conducted October 1, 1994, through September 30, 1999 at university, public, and private medical centers and clinics, 1639 HIV-seropositive and 452 seronegative women were evaluated every 6 months for up to 5 years using history, cervical cytology, T-cell subsets, and quantitative plasma HIV RNA. Human papillomavirus (HPV) typing at baseline was determined by polymerase chain reaction. Cytology was read using the Bethesda system, with any smear showing at least atypia considered abnormal. Poisson regression identified factors associated with incident cytologic abnormalities whereas logistic regression identified those associated with progression and regression after an abnormality., Results: At least one abnormal smear was found during all of follow-up among 73.0% of HIV-seropositive patients and 42.3% of seronegatives (p <.001). Only 5.9% of seropositives ever developed high-grade lesions, and the proportion with high-grade findings did not rise over time. Incidence of atypical squamous cells of uncertain significance (ASCUS) or more severe lesions among HIV-seropositive patients and seronegative patients was 26.4 and 11.0/100 woman-years (rate ratio [RR], 2.4; 95% confidence interval [CI], 1.9-3.0), whereas that of at least low-grade squamous intraepithelial lesions (SIL) was 8.9 and 2.2/100 (RR, 4.0; CI, 2.6-6.1). HIV status, detection of the presence of human papillomavirus (HPV), CD4 lymphocyte count, and HIV RNA level predicted incidence of abnormal cytology (p <.05); HPV detection and HIV RNA level predicted progression (p <.01); and HPV detection, CD4 lymphocyte count, and HIV RNA level predicted regression (p <.001). Rates of incidence, progression, and regression of abnormal cytology did not differ between HIV seronegative women and seropositive women with CD4 lymphocyte counts >200/mm(3) and HIV RNA levels <4000/ml of similar HPV status., Conclusions: Although HIV infected women were at high risk for abnormal cytology, high-grade changes were uncommon. HIV status, HPV detection, CD4 lymphocyte count, and HIV RNA level predicted the incidence of cervical cytologic abnormalities. Progression was significantly increased only among the most immunosuppressed women, while regression was significantly reduced in all HIV seropositive women except those with the best controlled HIV disease.

Objectives: The goals of this work were to describe the compliance with and acute hematologic toxic effects of chemoradiation for cervical cancer in indigent women and to explore the likelihood that chemoradiation is effective outside research settings. We hypothesized that if compliance and toxicity are not limiting in this high-risk group of patients, the effectiveness of chemoradiation for cervical cancer in community settings is likely to mirror the efficacy demonstrated in clinical trials., Methods: This study is a retrospective review of prospectively maintained data on women with newly diagnosed cervical cancer treated with chemoradiation between August 1998 and August 2000. Cisplatin was given weekly at 40 mg/m(2) to a maximum of six courses. A WBC count <3000/mm(3) resulted in cancellation of cisplatin but not radiation, and patients were transfused for hemoglobin <9 g/dl. Statistical analysis was performed using the t test, chi(2) test, and Fisher's exact test., Results: In all, 19 of 65 patients treated (29.2%) missed at least one chemotherapy cycle, with 10 (15.4%) due to missed appointments, 8 (12.3%) due to a low WBC count, and 1 due to increased creatinine. Nineteen patients (29.2%) received RBC transfusion during chemoradiation, and two (3%) had platelets <75,000/mm(3). Noncompliant patients had a lower mean total point A dose (7986 cGy vs 8413 cGy, P = 0.04) and longer overall treatment duration (79 days vs 51 days, P < 0.001). No patient had a fatal hematologic complication., Conclusion: Nearly a third of the indigent women treated with chemoradiation for cervical cancer do not complete the prescribed treatment, and a similar number require blood transfusions. In indigent and minority women, the effectiveness of chemoradiation protocols may not mirror the efficacy obtained in clinical trials., (Copyright 2001 Academic Press.)

Objective: The goal of this work was to compare characteristics and survival of cervical cancer patients at adjacent public and university hospitals to define the effects of poverty and ethnicity on disease., Methods: A retrospective chart review was conducted of cervical cancer patients managed by gynecologic oncologists at two adjacent urban hospitals between 1992 and 1998. Continuous variables were compared by t test, categorical variables by chi(2), and survival by the Kaplan-Meier and log-rank methods., Results: In all, 372 patients were identified, with 209 (56%) at the public hospital and 163 (44%) at the adjacent university hospital. Ethnic distribution differed between the two hospitals: 100 (52%) versus 46 (28%) African-American, 56 (29%) versus 13 (8%) Hispanic, 31 (16%) versus 96 (60%) Caucasian, and 5 (3%) versus 6 (4%) other (P < 0.001). In addition, public hospital patients presented with more advanced cancers (stages II--IV) than those managed at the university hospital, 96 (48%) versus 53 (34%) (P = 0.008), and squamous cancers were more common at the public hospital, 154 (89%) versus 120 (76%) (P = 0.03). However, with a median follow-up of 17 months, stage-adjusted survival did not differ between the two institutions., Conclusions: The higher proportions of advanced and squamous cervical cancers encountered at the public hospital likely reflect suboptimal screening. Equal access to gynecologic oncologists eliminated disparities in stage-adjusted survival. Efforts at earlier diagnosis should be directed at indigent, especially minority women., (Copyright 2001 Academic Press.)

Objective: To estimate compliance by indigent women with surveillance protocols after molar pregnancy., Methods: Women whose molar pregnancies were evacuated at an urban, public hospital were advised to return weekly either until hCG levels decreased below 5 mIU/mL, then monthly for 6 months, or until diagnosis and treatment of gestational trophoblastic disease, then monthly for 12 months. Hormone testing was by enzyme-linked immunosorbent assay. Statistical analysis was by chi(2) tests., Results: Of 51 women identified, 11 (22%) developed trophoblastic disease. All achieved remission after chemotherapy. Five (45%) of these 11 missed at least one treatment, seven (64%) missed at least one postremission visit, and none was fully compliant with protocols. Five (13%) of the 40 remaining women were lost to follow-up before remission. Seven (18%) of the 40 women who did not receive chemotherapy complied fully with protocols, whereas five (13%) were lost to follow-up before remission, and 16 (40%) were lost before completing 6 months of follow-up. Only 15 (29%) of the 51 women completed surveillance without gestational trophoblastic disease or pregnancy. Six women conceived, and injectable medroxyprogesterone acetate was associated with a lower pregnancy rate (zero of 25 compared with six of 26 (23%), P <.01)., Conclusion: Most indigent women failed to comply with postmolar surveillance, although most achieved remission. Injectable medroxyprogesterone acetate is recommended for postmolar contraception in this population.

To explore the relationship between vitamin A (retinol) deficiency and cervical squamous intraepithelial lesions (SILs) in human immunodeficiency virus (HIV)-infected women, we measured serum retinol concentrations in 1314 women enrolled in the Women's Interagency HIV Study and correlated the results with concurrent cervical cytology. At the baseline visit, 204 (15.5%) of the 1314 patients had retinol concentrations consistent with deficiency (<1.05 micromol/L). Analysis of Papanicolaou smears showed SILs in 216 (16.4%) of 1314 women. Cervical SILs were found to be associated with retinol concentrations <1.05 micromol/L (multivariate odds ratio [OR], 1.63; P=.04) in a multivariate model, which included human papillomavirus (HPV) status and markers of nutritional status and HIV disease stage. In the subset of women with genital HPV (n=774), a multivariate analysis again revealed a significant independent association between retinol <1.05 micromol/L and cervical SILs (multivariate OR, 1.75; P=.02). Our findings suggest that retinol deficiency may contribute to the development of cervical SILs in HIV-infected women.

The activity and toxicity of topotecan in women with recurrent cervical cancer are described from a case series of women with recurrent cervical cancer who had measurable disease and were not amenable to cure by surgery or radiation. All patients had prior platinum-based chemotherapy and developed progressive disease. Topotecan was given as 1 mg/m2/day over 30 min for 5 days every 3 weeks until progression of disease or prohibitive toxicity. Between July 1998 and July 1999, 12 patients received a total of 20 cycles of topotecan. Median age was 41 years (range 21-62), and 11 (92%) patients had prior whole pelvic radiation. The mean number of topotecan cycles was 1.5 (median 1, range 1-3). There were two partial responses (16.7%; 95% CI, 2% to 48%), both in prior radiation fields. Five patients required red blood cell transfusions, four had grade II nausea and vomiting, two developed sepsis (one with neutropenia), one developed fever, and one reported hyperpigmentation. There were no treatment-related mortalities. Although topotecan appears to exhibit modest activity in recurrent cervical cancer after radiation and platinum-based therapy, bone marrow toxicity may limit the utility of this regimen without hematopoietic growth factor support.

Objective: The objective of this study was to determine the impact of pretreatment tests on staging and management for women with bulky or clinically evident metastatic cervical cancer., Methods: Demographics and findings of clinic pelvic examination (PE), examination under anesthesia (EUA), chest x ray (CXR), abdominopelvic computed tomography (CT), and intravenous urography (IVU) were reviewed for women with primary, untreated cervical cancers either > or =4 cm or with extracervical disease apparent on PE or CXR evaluated between July 1, 1994, and March 31, 1999. Stage was assigned according to standards of the International Federation of Gynecology and Obstetrics., Results: In 133 women studied, tumor diameter averaged 4. 9 cm on PE and 5.7 cm at EUA (P = 0.0005). Of 92 women undergoing both PE and EUA, 30 (33%) had size discrepancies of more than 1 cm. Compared with EUA, PE had sensitivity, specificity, and positive and negative predictive values, respectively, of 65, 89, 79, and 81% for vaginal disease, 74, 91, 95, and 63% for parametrial disease, and 57, 90, 60, and 89% for sidewall fixation. CXR was abnormal in 5 (4%). IVU showed ureteral dilation in 20 (22%) of 90 women, while CT showed dilation in 34 (28%) of 123 women. CT also showed pelvic lymphadenopathy in 22 (18%) women and paraaortic lymphadenopathy in 12 (10%). Bladder biopsies showed malignancy in 8 (8%), including one transitional cell carcinoma of the bladder. Proctoscopy failed to reveal metastatic cervical cancer., Conclusions: CXR and EUA with cystoscopy are important to the accurate staging and treatment of bulky or clinically metastatic cervical cancers, while proctoscopy is rarely useful. CT predicts ureteral obstruction well, and its greater information yield may justify its higher cost compared with IVU., (Copyright 2000 Academic Press.)

Unlabelled: In the general population, nonadherence to the recommendation to have colposcopy in women with abnormal cytologic smears is estimated at 30% to 80%, but studies have failed to identify consistent risk factors for nonadherence. The purpose of this analysis is to assess adherence to colposcopy in a subset of participants in the Women's Interagency HIV Study (WIHS), an ongoing multisite longitudinal study of HIV infection in women in the United States and determine factors associated with nonadherence. Identification of such predictors would be useful in designing strategies to improve adherence in this group., Methods: Adherence to colposcopy was examined in a cohort of 462 women with, or at risk for, HIV infection with abnormal cervical cytology on entry into WIHS. Adherence was defined as having colposcopy done within 6 months of an abnormal cytology result., Results: Overall adherence to colposcopy was 65% (302 of 462). A multivariate logistic regression model revealed that the odds of adherence were significantly lower for the women who were HIV-infected (p = .011), current crack/cocaine users (p = .040), ever too ill to get medical care (p = .033), not recruited by WIHS study staff (p = .004), and less concerned about the care of their children (p = .037). Among HIV-seropositive women, low CD4 counts, high viral loads, and presence of AIDS-defining illness were not predictive of nonadherence., Discussion: Adherence to colposcopy among WIHS participants was at the upper limit of the reported range in the United States. Chemical dependency and domestic violence may negatively impact on colposcopy adherence whereas supportive study personnel, having health insurance, and concerns about raising one's children appear to be motivators for adherence to colposcopy in this study. HIV infection was a risk factor for nonadherence, but markers of advanced disease were not predictive of nonadherence.

Objective: The aim of this study was to report the value of chemoradiation in the management of cancers of the Bartholin gland., Methods: Primary treatment consisting of 45-46 Gy teletherapy radiation to the vulva, pelvis, and groins in combination with 50 mg/m(2) of cisplatin and 1000 mg/m(2)/day of 5-fluorouracil for 5 days during the first and fifth weeks of irradiation was delivered, followed by interstitial implant or excision., Results: Two patients were free of disease at 30 and 59 months following therapy. Both patients required myocutaneous flap closure, one after excision of tumor after radiation and one after radionecrosis at the implant site., Conclusions: Primary chemoradiation may allow continence-sparing therapy for women with primary carcinoma of the Bartholin gland., (Copyright 1999 Academic Press.)

Background: Acute lower extremity paralysis secondary to lumbosacral plexopathy is a rare but severe complication that may follow pelvic radiotherapy for cervical cancer., Case: A 49-year-old female with newly diagnosed stage IIIB cervical cancer developed progressive bilateral lower extremity paralysis and pelvic pain only 10 weeks following completion of radiation therapy for cervical cancer with no evidence of metastasis or progression of disease. Her bladder and bowel function were not affected. Following extensive workup, the most likely etiology was presumed radiation-induced lumbosacral plexopathy., Conclusion: Although metastatic carcinoma is more commonly the reason for progressive lower extremity weakness with pelvic pain in women with advanced cervical cancer, radiation-induced lumbosacral plexopathy, a rare but devastating complication, may be the cause. Diagnosis is by exclusion., (Copyright 1999 Academic Press.)

Objective: Our aim in this study was to determine the value of cervicovaginal cytology in surveillance for recurrent cervical cancer., Materials and Methods: Charts were reviewed for 136 women with cervical cancer presenting at least 3 months after treatment with curative intent for a previously scheduled surveillance visit to Cook County Hospital between September 1, 1994, and December 31, 1995. Results of cytology and symptoms elicited by history and physical examination were compared to recurrences occurring within 6 months., Results: Recurrences were identified in eight patients. Sites of recurrence included cervix-vaginal cuff (n = 5), pelvic wall (n = 1), and paraaortic or supraclavicular lymph nodes (n = 2). Sixteen women had symptoms, and seven had abnormal physical findings. One woman had malignant cytology. Sensitivity, specificity, and positive and negative predictive value were 38, 90, 23, and 96%, respectively, for symptoms; 50, 99, 80, and 97%, respectively, for examination; and 13, 100, 100, and 95%, respectively, for cytology., Conclusion: After cervical cancer treatment, cervicovaginal cytology was a more specific but less sensitive predictor of recurrence within 6 months than were symptoms or physical findings.

Objective: To determine correlates of compliance with follow-up recommendations after colposcopy., Methods: Between October 1, 1992, and June 30, 1997, management recommendations were made to 451 consecutive women who attended a resident colposcopy clinic. Compliance was determined after 8-12 months. Correlates of compliance were assessed by univariate and multivariate analyses., Results: Recommendations included repeat cytology in 6 months for 252 women, loop excision for 114, conization for 27, repeat colposcopy for 51, other for three, and not recorded for four. Rates of ever complying were 81% for loop excision, 85% for conization, 62% for repeat colposcopy, and 36% for repeat cytology. In multivariate analysis, the only significant predictors of compliance were history of genital herpes simplex infection (odds ratio [OR] 0.20; 95% confidence interval [CI] 0.05, 0.86, P = .03) and the nature of the recommendation (OR 4.73; CI 2.51, 8.92 for loop excision; OR 8.72; CI 2.57, 29.6 for conization; and OR 2.53; CI 1.30, 4.93 for repeat colposcopy, all against observation, P<.001)., Conclusion: After colposcopy, women were more likely to comply with earlier, more intensive interventions, although the relative effect of follow-up interval and intervention could not be distinguished.

Verrucous carcinomas of the vulva are rare and have not been reported in women infected with the human immunodeficiency virus. We present such a case in a 32-year-old woman characterized by bladder involvement that failed therapy with 13-cis-retinoic acid and interferon-alpha and required anterior exenteration., (Copyright 1999 Academic Press.)

Background: Cervical neoplasia occurs with increased frequency among women infected with HIV-1., Objective: To characterize prevalence of and risk factors for abnormal cervical cytology among women with HIV and to compare them to uninfected women., Methods: Baseline cervical cytology was obtained from 1713 women seropositive for HIV and 482 at-risk control women who were enrolled in the Women's Interagency HIV Study, a multicenter prospective cohort study conducted in six U.S. cities. Associations with sociodemographic, medical, and sexual variables were assessed by Fisher's exact test, Mantel extension test, and logistic regression analysis., Results: Cervical cytology was abnormal in 38.3% of HIV-infected women (atypical squamous cells of uncertain significance [ASCUS] 20.9%, low-grade squamous cells of uncertain significance [LSIL] 14.9%, high-grade squamous cells of uncertain significance [HSIL] 2.3%, cancer 0.2%) and 16.2% of HIV-uninfected women (ASCUS 12.7%, LSIL 2.3%, HSIL 1.2%, cancer 0.0%). Risk factors for any abnormal cytology in multivariate analysis included HIV infection, CD4 cell count, HIV RNA level, detection of human papillomavirus (HPV), a prior history of abnormal cytology, employment, and number of male sex partners within 6 months of enrollment. Prior abortion was associated with a decreased risk of cytologic abnormality., Conclusions: Cervical cytologic abnormalities were frequent among women infected with HIV, although high-grade changes were found in only 2.5%. Factors linked to sexual and reproductive history, HPV infection, and HIV disease all influenced risk.

Objective: To document the sexual and contraceptive practices of women with HIV infection or who are at risk for infection., Design: Data on the baseline behaviors of 561 HIV-negative and 2040 HIV-positive women were collected as part of the Women's Interagency HIV Study (WIHS). WIHS is a multisite, longitudinal study following the natural history of HIV infection among women in the United States., Methods: Each participant contributed an interviewer administered, self-report interview including questions on sexual and contraceptive behavior., Results: Women with HIV were less likely to report heterosexual activity in the previous 6 months (65% HIV-positive, 76% HIV-negative). Among sexually active women, there were no differences in the proportion of those reporting vaginal (97% HIV-positive, 98% HIV-negative) or anal sex (12% HIV-positive, 10% HIV-negative), although women with HIV were less likely to report cunnilingus (41% HIV-positive, 70% HIV-negative) and fellatio (48% HIV-positive, 57% HIV-negative). Of women with HIV, 63% always used condoms during vaginal sex (versus 28% HIV-negative), with lower rates reported during other sexual activities. Crack, cocaine, or injecting drug use, reported by 27% of HIV-positive and 35% of HIV-negative women, was associated with inconsistent condom use, independent of serostatus. HIV-positive women who reported using condoms and another contraception method were less consistent condom users (57% consistent versus 67%)., Conclusions: The prevalence of sexual risk behavior in this sample suggests that, although women with HIV exhibit lower levels of sexual risk behavior than uninfected women, many have not been successfully reached with regard to implementing safer behaviors. These findings have implications for more widespread and effective behavioral intervention efforts.

In this cross-sectional study, 53 cervicovaginal lavage samples (CVL) from 41 women were analyzed for the chemokines interleukin-8 (IL-8), regulated-on-activation normal T-expressed and secreted (RANTES) factor, and macrophage inflammatory protein-1alpha (MIP-1alpha) by enzyme-linked immunosorbent assay (ELISA). IL-8 was detected in 81% of CVL, whereas RANTES was detected in 32%, and MIP-1alpha in 15% of the CVL. The mean levels of IL-8, RANTES, and MIP-1alpha in positive samples were 396 pg/ml, 102 pg/ml, and 34 pg/ml, respectively. IL-8 levels correlated positively with IL-1beta and IgG in a subset of CVL samples. RANTES levels correlated positively with complement protein levels. Additionally, the levels of RANTES, but not MIP-1alpha, reached levels reported in previous studies of the effects of beta chemokines to inhibit HIV replication. These results suggest that measuring chemokines in CVL specimens can provide important information regarding immune responses in the genital tract.

Objective: Our goal was to identify risk factors for suboptimal excision in relation to a positive endocervical curettage (ECC) after conization or positive specimen margin., Materials and Methods: A retrospective review of referral cy-tology and colposcopy results for 280 women undergoing conization at two urban teaching centers was performed. Mann-Whitney or Pearson's chi-square test was used to de-termine significant associations between preoperative variables and positive cone margin, positive intraoperative ECC, and either positive margin or positive intraoperative ECC., Results: Cytology grade, gravidity, parity, and race were not significantly correlated with any outcome variable. Using lo-gistical regression analyses, correlates of positive ECC after conization included increasing age (p = .01), positive colpo-scopic biopsy (p = .01), colposcopic inadequacy (p = .01), and positive preoperative ECC (p = .03). Positive preoperative ECC was the only significant risk factor for positive cone margin (p = .02) or the combination of either positive intraoperative ECC or positive cone margin (p = .0001). Condusion. A positive preoperative ECC is the best predictor of suboptimal excision at conization and should be performed unless contraindi-cated.

Objectives: We set out to evaluate the predictive value of preoperative cytology and colposcopic histology in determining final pathology after conization of the cervix in the era of the Bethesda system., Methods: A retrospective review of the charts of 280 patients who had cold-knife conization was undertaken. Preoperative cytology and colposcopic biopsy histology were compared to the cone biopsy histology. The Spearman's correlation coefficient was used to determine the correlation between both preoperative cytology and histology and histology of the cone biopsy., Results: Pre-operative cytology matched cone histology in only 56.5% of cases and was within one grade in 92.3% of cases, with a correlation of 0.369. Most outliers were high-grade cytology not confirmed at cone biopsy. Preoperative biopsy correlated even less with cone histology: Exact correlation occurred in 40% of cases, correlation within one grade was seen in 69.4% of cases, and the Spearman correlation coefficient was 0.328. Most outliers were high-grade lesions on cone biopsy that were not detected with colposcopic biopsy., Conclusions: Pre-operative cytology and histology do not predict final pathology with enough accuracy to allow management to be determined by them. Conization of the cervix remains a useful procedure in the triage of the abnormal cytological smear.

We analyzed 21 cervicovaginal lavage (CVL) specimens from 19 women participating in the Women's Interagency HIV Study to characterize levels of antibody, cytokine, and complement and to determine associations between these levels and stage of the menstrual cycle, HIV status, and the presence of concurrent genital infection and genital dysplasia. Sixteen samples were collected from HIV-infected women and five from high-risk HIV-seronegative women. CVL fluid was assayed for levels of IgG, secretory IgA (s-IgA), interleukin 2 (IL-2), IL-10, IL-6, tumor necrosis factor alpha (TNF-alpha), IL-1beta, interferon gamma (IFN-gamma), C3, C1q, and C4. Women with HIV were more likely to have cervicovaginal dysplasia (9/16 vs. 0/5; p = 0.027) but were not more likely to have concurrent vaginal infection (10/16 vs. 2/5; p = 0.38). Antibody, cytokine, and complement were detectable in all samples, although not all samples had measurable IL-10, C3, or C4. HIV-infected women demonstrated a trend toward higher levels of IFN-gamma than did uninfected women (p = 0.098); no differences were noted in other parameters. HIV-infected women with vaginal infections had significantly higher CVL levels of IgG (p = 0.023) and IFN-gamma (p = 0.02) than did HIV-infected women without genital infections. HIV-infected women with cervicovaginal dysplasia were found to have higher levels of IL-1beta (p = 0.045) and IFN-gamma (p = 0.039) than those without. Analysis of the HIV-infected cohort by CD4 cell count revealed higher levels of IgG and IFN-gamma in CVL from women with lower CD4 cell counts, although these differences were not statistically significant. Higher levels of proinflammatory cytokines in CVL fluid of women with genital infection or cervicovaginal dysplasia may affect local HIV replication and may influence the risk of acquisition or transmission of HIV for women with these underlying conditions.

Objective and Design: To determine whether the female genital tract contains factors that affect HIV-1 replication. Cervicovaginal lavage (CVL) samples were collected from HIV-1-seropositive and seronegative women and added to cell cultures., Methods: HIV p24 production was used to measure the effects of CVL on replication of HIVMN in a T-cell line, of a primary isolate in peripheral blood mononuclear cells, or on HIV expression by the latently-infected monocytic U1 cell line. The effects of CVL on the HIV long terminal repeat (LTR) were determined in 1G5 T cells by measuring luciferase activity., Results: Increased replication of HIVMN and a primary isolate were observed in T cells cultured with CVL samples from three out of 38 HIV-infected women, one out of four uninfected high-risk women, and none of 12 low-risk women. The CVL factor increased replication by enhancing virus expression via activation of the HIV LTR. The HIV-inducing activity was highly stable to heat but was sensitive to proteases, indicating that the activity was distinct from heat-labile cytokines including tumour necrosis factor-alpha., Conclusions: This is the first study to show that a factor which can stimulate HIV-1 replication is present at biologically active levels in the reproductive tract of women. This factor could potentially affect sexual or vertical transmission of HIV-1 by altering genital tract virus load or virus expression.

Background: Concern about false negative screening cytology has led to the development of adjunctive tests, among them speculoscopy. Speculoscopy involves cervical examination after acetic acid wash with 5X magnifying loupes under chemiluminescent illumination., Conclusions: Limited data support a role for speculoscopy to improve screening yield and allow triage of patients with borderline cytology, but indications and strategies for use require further definition.

Objective: To correlate operative indications for and histologic findings of cold knife cone biopsy since introduction of the Bethesda system for classification of cervical cytology., Methods: Patients undergoing cold knife conization of the cervix at adjacent urban medical centers were identified from operating logs. Data on indication and outcome were tabulated retrospectively for 294 women., Results: Cone biopsy indications were sometimes multiple and included dysplastic or malignant endocervical curettage (ECC) in 66%, inadequate colposcopy in 48%, cytologic:histologic discrepancy in 16%, and suspicion of invasive cancer on biopsy in 1% of cone biopsies. For 8% of patients, none of these indications were found. The respective proportions of women with benign findings or atypical, low-grade dysplasia, high-grade dysplasia, or cancer was 16, 15, 65, and 3% for positive ECC, 26, 16, 54, and 4% for inadequate colposcopy, 22, 17, 59, and 0% for discrepancy, and 0, 0, 100, and 0% for suspicion of cancer on cytology. Outcomes were significantly worse among women with positive ECC (OR = 2.1, P = 0.006)., Conclusions: The likelihood of identifying high-grade lesions in cone biopsy specimens is high, especially among women with a positive ECC, but the risk of cancer is low.