Statin use in older adults with cancer - Experience from a dedicated geriatric oncology service.

INTRODUCTION: The increase in statin use, since their introduction, has been rapid and the broadening of indications has occurred seemingly without restriction. Once established on statin therapy, there is sparse research on discontinuation. Trials do not often address benefit in later life, or the impact of a life-limiting diagnosis. Data on primary prevention suggest that 100 patients need treatment for 2.5 years to prevent one major adverse cardiovascular event. Acknowledging this, we sought to determine the use of statins in a cohort of older adults with cancer, to highlight prevalence, and suggest a role for deprescribing. MATERIALS AND METHODS: Data were retrospectively collected from a prospectively maintained database of patients attending a single centre Geriatric Oncology clinic. Data collected included sex, age, cancer type and stage, systemic anti-cancer therapy (SACT) recommendation, comorbidities, non-SACT medications, and overall survival. For those receiving statin therapy, data were separated into primary prevention and stage IV cancer. RESULTS: In the group studied (n = 230), 135 (59%) were prescribed a statin, with 79 (58%) for primary prevention. Ninety-three (40%) had stage IV cancer. Of the 230 patients, 134 (58%) were recommended SACT. Within the primary prevention group, the median age was 79 years. Twenty-seven patients (34%) had stage III disease, while 36 (46%) had stage IV disease. Thirteen (16%) had diabetes mellitus. The median number of medications was seven (Interquartile range 5). Fifty patients (63%) were recommended SACT. In terms of survival, 31 (50%) were alive at one year, 18 (29%) alive at two years, and 14 (23%) alive beyond two and a half years. Within the stage IV disease group, 59 out of 93 (63%) were receiving statin therapy; 35 (59%) for primary prevention and seven (8%) for diabetes mellitus. Fifty-eight (63%) were recommended SACT. Twenty-four (29%) were alive at one year, 17 (21%) alive at two years, and 13 (16%) alive beyond two and a half years. DISCUSSION: Statin therapy is prevalent and continues into older age. Available data regarding statin therapy in older adults and survival seen in this study support deprescribing in primary prevention and life-limiting illness, such as stage IV cancer.

The LAST Project and the diagnostic bottom line.

The LAST Project's consensus recommendations for terminology and biomarker use to improve the accuracy and reproducibility of histopathological diagnoses for HPV-associated squamous intraepithelial lesions of the lower anogenital tract are reviewed.

Factors associated with prevalent abnormal anal cytology in a large cohort of HIV-infected adults in the United States.

BACKGROUND: The prevalence of and risk factors for abnormal anal cytology among men and women with human immunodeficiency virus (HIV) infection have not been extensively investigated. METHODS: The Study to Understand the Natural History of HIV and AIDS in the Era of Effective Therapy (SUN study) is a prospective cohort study of HIV-infected patients in 4 US cities. Baseline questionnaires were administered and anal samples for cytology and human papillomavirus (HPV) detection and genotyping were collected. RESULTS: Among 471 men and 150 women (median age, 41 years), 78% of participants were receiving combination antiretroviral therapy, 41% had a CD4(+) cell count of ≥500 cells/µL, and 71% had an HIV RNA viral load of <400 copies/mL. The anal cytology results were as follows: 336 participants (54%) had negative results, 96 participants (15%) had atypical squamous cells, 149 participants (24%) had low-grade squamous intraepithelial lesions, and 40 participants (6%) had high-grade squamous intraepithelial lesions. In a multivariate analysis, abnormal anal cytology was associated with number of high-risk and low-risk HPV types (adjusted odds ratio [AOR] for both, 1.28; P < .001), nadir CD4(+) cell count of <50 cells/µL (AOR, 2.38; P = .001), baseline CD4(+) cell count of <500 cells/µL (AOR, 1.75; P = .004), and ever having receptive anal intercourse (AOR, 2.51; P < .001). CONCLUSION: HIV-infected persons with multiple anal HPV types or a nadir CD4(+) cell count of <50 cells/µL have an increased risk for abnormal anal cytology.

Evolving immunosuppressive microenvironment during human cervical carcinogenesis.

Chronic infection with human papillomavirus (HPV) can result in cervical cancer. To understand how HPV escapes immune eradication, we examined biophenotypes of immune cells in human normal cervix, cervical intraepithelial neoplasia (CIN), and cancer. Expression and cellular localization of Forkhead box protein-3 (FOXP3), indolamine 2,3-dioxygenase (IDO), interleukin (IL)-10, and interferon (IFN)-gamma were examined by immunofluorescence and immunohistochemistry. Mean cell densities of stromal FOXP3+ cells, IDO+ cells, IL-10+ cells, CD1a+ cells, and macrophages significantly increased from normal cervix to cancer, whereas densities of IFN-gamma+ and MMP-9+ cells increased from normal cervix to CIN but decreased in cancer. Flow cytometry confirmed significant elevation of cervical T cells expressing IFN-gamma and transforming growth factor-beta in CIN compared with normal cervix. Upon activation, a significantly increased proportion of cervical T cells expressed IFN-gamma in CIN than normal. A unique subset of morphologically immature stromal dendritic cells expressing IL-10 and IDO was more numerous in cancer than in normal cervix and CIN. The potentially suppressive immune milieu in the cervix may be permissive of HPV-associated cervical carcinogenesis.

Participants at the ASCCP 2000 Biennial Meeting adhere to published guidelines in their management of atypical squamous cells and atypical glandular cells on pap test.

OBJECTIVE: To determine practice patterns of the American Society for Colposcopy and Cervical Pathology (ASCCP) 2000 Biennial Meeting participants for management of women with atypical squamous cells of undetermined significance (ASCUS) and atypical glandular cells of undetermined significance (AGUS). MATERIALS AND METHODS: A three-page survey was developed to query participants about their standard practices for managing atypical squamous cells and atypical glandular cells on Pap tests; use of human papillomavirus testing; and use of vaginal estrogen cream in postmenopausal women before follow-up. RESULTS: There were 217 completed surveys (47.0% response rate). Responses of 194 qualified surveys are presented here. For women with first-time ASCUS (unqualified) and no previous history of cervical intraepithelial neoplasia (CIN), 16.4% of respondents would perform colposcopy. For ASCUS (favor squamous intraepithelial lesion [SIL]), a significantly higher percent, 74.9%, would proceed immediately to colposcopy (p < .001). For ASCUS (unqualified or favor SIL) in a woman with a previous history of CIN, 82.7% and 95.5% would perform colposcopy, respectively (p < .001). For a patient with AGUS, 97.5% would perform colposcopy (with or without endocervical curettage or endometrial biopsy). Human papillomavirus testing was seldom used in the management of ASCUS (10.4%) and AGUS (7.8%). CONCLUSIONS: Participants at the 2000 ASCCP Biennial Meeting made clear distinctions between ASCUS and AGUS in managing women with abnormalities on Pap, and management was consistent with guidelines published by the ASCCP, American College of Obstetricians and Gynecologists, and the National Cancer Institute.

Effect of highly active antiretroviral therapy on the natural history of anal squamous intraepithelial lesions and anal human papillomavirus infection.

The effect of highly active antiretroviral therapy (HAART) on the natural history of anal squamous intraepithelial lesions (ASIL)-the likely anal cancer precursor-and anal human papillomavirus (HPV) infection is unknown. ASIL severity and level of anal HPV DNA were evaluated among HIV-positive men who have sex with men (MSM) for at least 6 months before initiation of HAART. The results were compared with those from a 6-month period after initiation of HAART. Anal swabs for cytology and HPV studies were obtained, followed by high-resolution anoscopy and biopsy. Among men whose most severe pre-HAART diagnosis was atypical squamous cells of undetermined significance or low-grade ASIL, 18% (confidence interval [CI], 6-31%, 7 of 38) progressed and 21% (CI, 8-34%, 8 of 38) regressed 6 months after starting HAART. Seventeen percent (CI, 0-38%, 2 of 12) of study subjects who began with a normal diagnosis developed ASIL. Only 4% (CI, 0-10%, 1 of 28) of study subjects with high-grade ASIL regressed to normal. There was no reduction in the proportion of study subjects who tested positive for HPV DNA or HPV DNA levels after HAART initiation. The ASIL and HPV data were similar to those of the pre-HAART comparison period. These results indicate that HAART has little effect on either ASIL or HPV in the first 6 months after HAART initiation.

Risks for incident human papillomavirus infection and low-grade squamous intraepithelial lesion development in young females.

CONTEXT: Low-grade squamous intraepithelial lesions (LSILs) have been described as a benign cytological consequence of active human papillomavirus (HPV) replication. Several studies have reported that certain behavioral and biological risks exist for LSIL, suggesting that HPV alone is not sufficient for the development of LSIL. However, because most of these studies have been cross-sectional, it is not known whether behavioral and biological risks are simply risks for HPV infection itself. OBJECTIVE: To prospectively examine risks of incident HPV infection in HPV-negative females and of incident LSIL development in females with HPV infection. DESIGN: Prospective cohort study conducted between 1990-2000, with a median follow-up of 50 months. SETTING AND PARTICIPANTS: Females aged 13 to 21 years who attended 2 family planning clinics in the San Francisco bay area; 496 had prevalent HPV infection and 105 were HPV-negative. MAIN OUTCOME MEASURE: Incident development of HPV infection and LSIL, analyzed by various demographic, behavioral, and clinical risk factors. RESULTS: Fifty-four incident HPV infections occurred in the 105 females who were HPV-negative at study entry (median duration of follow-up for those who remained HPV-negative was 26 months). Multivariable analysis showed that risks of HPV included sexual behavior (relative hazard [RH], 10.10; 95% confidence interval [CI], 3.24-31.50 per new partner per month), history of herpes simplex virus (RH, 3.54; 95% CI, 1.37-9.10), and history of vulvar warts (RH, 2.73; 95% CI, 1.27-5.87). Current use of oral contraceptives had a significantly protective effect (RH, 0.49; 95% CI, 0.28-0.86). Among the 496 individuals who were HPV-positive at baseline or in follow-up, there were 109 incident cases of LSIL during the follow-up interval, with a median follow-up time of 60 months for those who never developed LSIL. Human papillomavirus infection was the most significant risk factor for development of LSIL. The multivariable model showed the following risks for LSIL: HPV infection for less than 1 year (RH, 7.40; 95% CI, 4.74-11.57); HPV infection for 1 to 2 years (RH, 10.27; 95% CI, 5.64-18.69); HPV infection for 2 to 3 years (RH, 6.11; 95% CI, 1.86-20.06); and daily cigarette smoking (RH, 1.67; 95% CI, 1.12-2.48). CONCLUSION: Our results indicate distinct risks for HPV and LSIL. In addition, most women with HPV infection in our study did not develop LSIL within a median follow-up period of 60 months. These findings underscore the hypothesis that certain biological risks thought to be associated with LSIL are, in fact, risks for acquisition of HPV. Cigarette smoking was a risk specific to LSIL, supporting the role of tobacco in neoplastic development.

Prevalence and risk factors for anal squamous intraepithelial lesions in women.

BACKGROUND: Anal cancers are thought to arise from squamous intraepithelial lesions in the anal canal, and women infected with human immunodeficiency virus-1 (HIV) may be at higher risk of anal cancer. Our aim was to determine the prevalence of human papillomavirus (HPV)-related abnormalities of the anal canal in women and to characterize risk factors for these lesions. METHODS: We evaluated HPV-related abnormalities in 251 HIV-positive and in 68 HIV-negative women. We completed physical examinations and obtained questionnaire data on medical history and relevant sexual practices. Univariate and adjusted relative risks (RRs) and 95% confidence intervals (CIs) were computed using the Mantel-Haenszel procedure and regression techniques. All statistical tests were two-sided. RESULTS: Abnormal anal cytology, including atypical squamous cells of undetermined significance, low-grade squamous intraepithelial lesions, or high-grade squamous intraepithelial lesions (HSILs), was diagnosed in 26% of HIV-positive and in 8% of HIV-negative women. HSILs were detected by histology or cytology in 6% of HIV-positive and in 2% of HIV-negative women. HIV-positive women showed increased risk of anal disease as the CD4 count decreased (P<.0001) and as the plasma HIV RNA viral load increased (P =.02). HIV-positive women with abnormal cervical cytology had an increased risk of abnormal anal cytology at the same visit (RR = 2.2; 95% CI = 1.4 to 3.3). Abnormal anal cytology in HIV-positive women was associated with anal HPV RNA detected by the polymerase chain reaction and by a nonamplification-based test (RR = 4.3; 95% CI = 1.6 to 11). In a multivariate analysis, the history of anal intercourse and concurrent abnormal cervical cytology also were statistically significantly (P =.05) associated with abnormal anal cytology. CONCLUSIONS: HIV-positive women had a higher risk of abnormal anal cytology than did HIV-negative women with high-risk lifestyle factors. These data provide strong support for anoscopic and histologic assessment and careful follow-up of women with abnormal anal lesions.

Detection of genetic changes in anal intraepithelial neoplasia (AIN) of HIV-positive and HIV-negative men.

Compared with HIV-negative individuals, HIV-positive individuals have a higher prevalence of anogenital human papillomavirus (HPV) infection, as well as a higher incidence of HPV-associated anal cancer. Little is currently known of chromosomal changes occurring in anal intraepithelial neoplasia (AIN), the probable precursor to anal cancer. Genetic changes in AIN were characterized by comparative genomic hybridization (CGH) in a study of samples obtained from 19 HIV-positive and 11 HIV-negative men. The proportion with genetic changes significantly increased with the severity of the histopathologic grade with none diagnosed as (0%) AIN 1; 5 of 17 (29%) as AIN 2; and 5 of 9 (56%) AIN 3 showing genetic changes (p = .02). This correlation was also found in study subjects who had multiple biopsies with different grades of pathology concurrently or serially over time. The most common regional DNA copy number change was gain mapped to chromosome arm 3q (12% of AIN 2 and 33% of AIN 3). This alteration was previously reported to be commonest alteration in cervical cancer, which suggests a common molecular pathway for these two HPV-associated anogenital neoplasias.

Correlating Papanicolaou Smear, Colposcopic Impression, and Biopsy: Results from the Women's Interagency HIV Study.

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.

Angiogenesis, proliferation, and apoptosis in anal high-grade squamous intraepithelial lesions.

PURPOSE: Management of anal high-grade squamous intraepithelial lesions is controversial. Anal and cervical high-grade squamous intraepithelial lesions are similar in that they occur in transitional squamous epithelium, are associated with human papilloma virus infection, and have increased incidence in the immunocompromised population. Ablation of cervical high-grade squamous intraepithelial lesions is preferred, but similar ablation or excision of anal high-grade squamous intraepithelial lesions may compromise bowel control; thus, there is a need to define the malignant potential of anal high-grade squamous intraepithelial lesions. METHODS: We analyzed 50 paraffin sections of normal anoderm, anal low-grade squamous intraepithelial lesions, high-grade squamous intraepithelial lesions, and anal squamous-cell carcinoma. Microvessels were detected immunohistochemically with von Willebrand factor and counted manually along the epithelial-stromal junction. Proliferation and apoptosis were determined in the epithelial cells with MIB-1 antibody immunostaining and the terminal deoxynucleotidyl transferase-mediated digoxigenin-11-dUTP nick end labeling, respectively. RESULTS: Microvascular density was significantly greater in anal high-grade squamous intraepithelial lesions (mean, 0.50 vessels/cm) vs. normal anoderm (mean, 0.21 vessels/cm; P = 0.0017, Mann-Whitney U test). The proliferative percentages were greater in low-grade squamous intraepithelial lesions, high-grade squamous intraepithelial lesions, and squamous-cell carcinoma (mean, 20.4, 21.8, and 23.6 percent) vs. normal anoderm (mean, 14.4 percent), although not significantly (P = 0.06, Kruskal-Wallis statistic). Although the mean proliferative proportions were similar in low-grade squamous intraepithelial lesions and high-grade squamous intraepithelial lesions, the apoptotic proportion was lower for high-grade squamous intraepithelial lesions than low-grade squamous intraepithelial lesions (10.13 vs. 19.96 percent, respectively; P = NS, Mann-Whitney U test). CONCLUSIONS: Angiogenesis, increased proliferation, and decreased apoptosis occur in anal high-grade squamous intraepithelial lesions as they do in the cervix before the development of malignancy. These biologic markers support the importance of anal high-grade squamous intraepithelial lesions as a potential premalignant lesion warranting surgical intervention.

Prevalence of and risks for cervical human papillomavirus infection and squamous intraepithelial lesions in adolescent girls: impact of infection with human immunodeficiency virus.

CONTEXT: Data suggest that in adults, human papillomavirus (HPV) infections and their sequalae, squamous intraepithelial lesions (SILs), occur more commonly among human immunodeficiency (HIV)-infected women because of the HIV-associated CD4+ T-cell immunosuppression. Since adolescents are more likely to be early in the course of HIV and HPV infections, the study of both infections in this age group may help elucidate their initial relationship. OBJECTIVE: To examine the prevalence of and risks for cervical HPV infection and SILs by HIV status in a population of adolescent girls. PARTICIPANTS: Subjects recruited at each of the 16 different US sites participating in a national study of HIV infection in adolescents. MAIN OUTCOME MEASURES: Cervical HPV DNA findings using polymerase chain reaction detection techniques and Papanicolaou smear from baseline visits. Infection with HPV was categorized into low- (rarely associated with cancer) and high- (commonly associated with cancers) risk types. RESULTS: Of 133 HIV-infected girls, 103 (77.4%) compared with 30 (54.5%) of 55 noninfected girls were positive for HPV (relative risk [RR], 1.4; 95% confidence interval [CI], 1.1-1.8). The risk was for high-risk (RR, 1.8; 95% CI, 1.2-2.7) but not low-risk (RR, 1.2; 95% Cl, 0.4-3.9) HPV types. Among the girls with HPV infection, 21 (70.0%) of the non-HIV-infected girls had normal cytologic findings compared with only 29 (29.9%) of the HIV-infected girls (P<.001). Multivariate analysis showed that HIV status was a significant risk for HPV infection (odds ratio [OR], 3.3; 95% CI, 1.6-6.7) and SIL (OR, 4.7; 95% CI, 1.8-14.8), but CD4 cell count and viral load were not associated with infection or squamous intraepithelial lesions. Only 9 girls had a CD4+ T-cell count of less than 0.2 cell X 10(9)/L. CONCLUSIONS: High prevalence of HPV infection in both groups underscores the risky sexual behavior in this adolescent cohort. Rates of HPV infection and SILs were higher among HIV-infected girls, despite similar sexual risk behaviors and the relatively healthy state of our HIV-infected group. Infection with HIV may enhance HPV proliferation through mechanisms other than CD4 immunosuppression, particularly early in the course of HIV infection.

Interrater Variability in Diagnosis of Cervical Biopsies from Women with HIV-1: Results from the Women's Interagency HIV Study.

OBJECTIVES: To determine interrater variability in classifying cervical biopsies from women with human immunodeficiency virus (HIV). MATERIALS AND METHODS: Cervical biopsies performed on women participating in the Women's Interagency HIV Study (WIHS) were read at the six participating sites. A 10% random sample was retrieved and reviewed using standardized terminology by pathologists with a special interest in gynecologic pathology. Results were compared with kappa values and Mantel-Haentzel tests. RESULTS: Biopsies from 288 HIV-seropositive and 24 HIV-seronegative women were reviewed. The weighted kappa value of 0.67 indicated moderate to strong agreement between original and review diagnoses, with a range of 0.54 to 0.84 across sites. No cancers were identified. Significantly more specimens showing cervical intraepithelial neoplasia (CIN) grade 2 or 3 were identified by review pathologists (p = .02). CIN2 or CIN3 was graded less severely by local pathologists in 18 (51%) of 35 cases, all from HIV-seropositive women. Local pathologists' diagnoses of CIN2 or CIN3 were downgraded by reviewers in 4 of 21 cases (19%). Discrepancies were more common among women with lower CD4 lymphocyte counts. CONCLUSIONS: Although discrepancies occur, interrater correlation in the interpretation of cervical biopsies from women with HIV is moderate to strong.

The significance of squamous metaplasia in the development of low grade squamous intraepithelial lesions in young women.

BACKGROUND: The purpose of this study was to examine, prospectively, the presence and extent of cervical epithelial immaturity as well as the rate of squamous metaplastic activity as a risk for the development of low grade squamous intraepithelial lesions (LSIL). METHODS: The study was a nested case-control design that used subjects from an ongoing cohort study of human papillomavirus infection. Fifty-four sexually active young women who developed LSIL were matched for age and number of visits with 54 women who had never developed LSIL. The percent of cervical immaturity was interpreted from colpophotography using a computer-generated pixel count of delineated immature and total cervical areas. Activity of squamous metaplasia was interpreted as the percent change in the area of immaturity over a defined time period. Conditional logistic regression analysis examined risks for the development of LSIL. RESULTS: Baseline area of biologic immaturity was not a predictor of LSIL. However, women with the a high degree of metaplastic activity near the SIL event were more likely to develop LSIL (odds ratio = 3.01 [95% confidence interval, 1.3, 6.8] for every 10% unit change in area of immaturity). CONCLUSIONS: A rapid rate of metaplastic change within the transformation zone, rather than the initial area of biologic immaturity, is a significant risk factor for the development of LSIL.

Risk factors for abnormal anal cytology in young heterosexual women.

Although anal cancers are up to four times more common in women than men, little is known about the natural history of anal human papillomavirus (HPV) infections and HPV-related anal lesions in women. This study reports on the prevalence of and risks for anal cytological abnormalities over a 1-year period in a cohort of young women participating in a study of the natural history of cervical HPV infection. In addition to their regularly scheduled sexual behavior interviews and cervical testing, consenting women received anal HPV DNA and cytological testing. Anal cytology smears were obtained from 410 women whose mean age was 22.5 +/- 2.5 years at the onset of the study. Sixteen women (3.9%) were found to have abnormal anal cytology: 4 women had low-grade squamous intraepithelial lesions (SILs) or condyloma; and 12 women had atypical cells of undetermined significance. Factors found to be significantly associated with abnormal anal cytology were a history of anal sex [odds ratio (OR), 6.90; 95% confidence interval (CI), 1.7-47.2], a history of cervical SILs (OR, 4.13; 95% CI, 1.3-14.9), and a current anal HPV infection (OR, 12.28; 95% CI, 3.9-43.5). The strong association between anal intercourse and the development of HPV-induced SILs supports the role of sexual transmission of HPV in anal SILs. Young women who had engaged in anal intercourse or had a history of cervical SILs were found to be at highest risk.

Atypical squamous cells of undetermined significance: management patterns at an academic medical center.

OBJECTIVE: Our intent was to compare the management of patients with atypical squamous cells of undetermined significance on cytologic screening at an academic center to published guidelines. STUDY DESIGN: We reviewed the management of 223 atypical squamous cells of undetermined significance cervical smears. Patients with a history of dysplasia were excluded. The time interval to and nature of follow-up testing was determined, and the influence of atypical squamous cells of undetermined significance qualifiers and provider specialty analyzed. RESULTS: Initial follow-up consisted of repeat cytologic examination alone in 94% of cases. Of patients with follow-up, 29% were retested within 2 months and 68% within 4 months. No conclusive differences in management were found by qualifier type or by provider specialty. Subsequent high-grade dysplasia was found in 2.6% of patients. CONCLUSIONS: A discrepancy exists between published guidelines and actual management of patients with atypical squamous cells of undetermined significance smears at this medical center. Patients often undergo follow-up testing at shorter intervals than those suggested despite a low likelihood of finding high-grade disease.

Virologic, immunologic, and clinical parameters in the incidence and progression of anal squamous intraepithelial lesions in HIV-positive and HIV-negative homosexual men.

Anal cancer may be preceded by anal squamous intraepithelial lesions (ASIL), but the natural history of ASIL is poorly understood. In this report, we characterize the 2-year incidence and progression of low-grade SIL (LSIL) and high-grade SIL (HSIL) in a cohort study in 346 HIV-positive and 262 HIV-negative homosexual or bisexual men. Subjects were studied at defined intervals using anal cytology, anoscopy with biopsy of visible lesions, human papillomavirus (HPV) testing, HIV serostatus, CD4 level, and data on medical history and lifestyle. The incidence of HSIL within 2 years was 20% in HIV-positive men and 8% in HIV-negative men who were normal at baseline. In total, 62% of HIV-positive and 36% of HIV-negative men with LSIL at baseline progressed to HSIL. The relative risk (RR) for anal disease progression in HIV-positive men was 2.4 (95% confidence interval [CI], 1.8-3.2) when compared with HIV-negative men. The RR increased to 3.1 (95% CI, 2.3-4.1) in HIV-positive men with CD4 counts <200/mm3. Infection with multiple HPV types was a risk factor for anal disease progression in both HIV-positive (RR = 2.0; 95% CI, 1.0-4.1) and HIV-negative (RR = 5.1; 95% CI, 2.3-11) men. The incidence of anal HSIL and progression of LSIL to HSIL within 2 years of follow-up is high in HIV-positive homosexual or bisexual men and to a lesser extent, in HIV-negative men. Men with the above risk factors may be at increased risk of developing anal cancer.

Anal squamous intraepithelial lesions in HIV-positive and HIV-negative homosexual and bisexual men: prevalence and risk factors.

Anal cancer is more commonly found in homosexual and bisexual men than cervical cancer is in women. Invasive anal cancer may be preceded by anal squamous intraepithelial lesions (ASIL), and treatment of ASIL may prevent the development of anal cancer. We characterized the prevalence and risk factors for ASIL in 346 HIV-positive and 262 HIV-negative homosexual men. Anal cytology, biopsy of visible anal lesions, and human papillomavirus (HPV) tests were performed, and data on HIV serostatus, CD4 count, and medical and lifestyle history were collected. ASIL was diagnosed in 36% of HIV-positive men and 7% of HIV-negative men (relative risk [RR] = 5.7; 95% confidence interval [CI], 3.6-8.9). Among HIV-positive men, the RR for ASIL increased with lower CD4 levels but was elevated even in men with CD4 levels >500/mm3 (RR = 3.8; 95% CI, 2.1-6.7) when compared with HIV-negative men. High-level HPV infection, as measured by detection of both hybrid capture (HC) group A and group B types, was another significant risk factor for ASIL in both HIV-positive men (RR = 8.8; 95% CI, 2.3-35) and HIV-negative men (RR = 20; 95% CI, 5.5-71) when compared with HC-negative men. HIV-negative men with anal HPV infection and HIV-positive men, regardless of CD4 level, are at high risk for ASIL.

High incidence of anal high-grade squamous intra-epithelial lesions among HIV-positive and HIV-negative homosexual and bisexual men.

OBJECTIVE: The incidence of anal cancer among homosexual men exceeds that of cervical cancer in women, and HIV-positive homosexual men may be at even higher risk than HIV-negative men. Cervical cancer is preceded by high-grade squamous intra-epithelial lesions (HSIL) and anal HSIL may similarly be the precursor to anal cancer. In this study, we describe the incidence of and risk factors for HSIL in HIV-positive and HIV-negative homosexual and bisexual men. DESIGN: Prospective cohort study of HIV-positive and HIV-negative homosexual men. SETTING: The University of California, San Francisco. PATIENTS: 346 HIV-positive and 262 HIV-negative men enrolled at baseline, 277 HIV-positive and 221 HIV-negative homosexual men followed after baseline. STUDY DESIGN: A questionnaire was administered detailing lifestyle habits, medical history and sexual practices. Anal swabs for cytology and human papillomavirus studies were obtained, followed by biopsies of visible lesions. Human papillomavirus testing was performed using polymerase chain reaction (PCR) and 'hybrid capture'. Blood was obtained for HIV testing and measurement of CD4 levels. MAIN OUTCOME MEASURES: Incident HSIL. RESULTS: HIV-positive men were more likely to develop HSIL than HIV-negative men relative risk (RR), 3.7; 95% confidence interval (CI), 2.6-5.7. Life-table estimates of the 4-year incidence of HSIL was 49% (95% CI, 41-56) among HIV-positive men and 17% (95% CI, 12-23) among HIV-negative men. Among HIV-positive men, those with lower baseline CD4 counts (P = 0.007) and persistent infection with one or more human papillomavirus types, determined using PCR (P = 0.0001), were more likely to develop HSIL. CONCLUSIONS: HIV infection, lower CD4 levels and human papillomavirus infection were associated with high rates of incident HSIL among homosexual men. However, high rates were found at all CD4 levels among HIV-positive men and among HIV-negative men.