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Background: Human papillomavirus (HPV)-associated anal cancer is increasing in prevalence and is more common among men who have sex with men and HIV-positive individuals than cervical cancer is among women in the United States. Cytology screening can detect the anal cancer precursor, anal intraepithelial neoplasia (AIN). Little is known about self-collected samples for AIN screening, and few community-based AIN estimates exist. Objective: To compare the sensitivity of self-collected versus clinician-collected anal cytology specimens to detect biopsy-confirmed AIN and the prevalence estimate of AIN in a community sample. Design: Cross-sectional study. Participants were mailed anal cytology self-collection kits with instructions. Clinicians repeated anal cytology and performed high-resolution anoscopy with biopsies as the diagnostic reference standard. Setting: San Francisco, California. Patients: Community-based sample of men who have sex with men. Measurements: Prevalence of anal HPV and AIN. Sensitivity and specificity of self-collected and clinician-collected anal cytology specimens to diagnose AIN were calculated. Results: Biopsy-proven AIN was diagnosed in 57% of HIV-positive and 35% of HIV-negative participants (P = 0.04), and 80% provided adequate self-collected specimens for interpretation. The sensitivity of cytology to detect AIN in HIV-positive men was 75% (95% CI, 51% to 93%) when self-collected and 90% (CI, 68% to 99%) when clinician-collected; respective values in HIV-negative men were 48% (CI, 26% to 70%) and 62% (CI, 38% to 82%). The specificity of cytology to detect AIN in HIV-positive men was 50% (CI, 22% to 78%) when self-collected and 64% (CI, 36% to 86%) when clinician-collected; respective values in HIV-negative men were 86% (CI, 71% to 94%) and 85% (CI, 72% to 93%). Limitations: The study sample was from a narrowly defined geographical area. Participants self-reported HIV status. Conclusion: In a community-based sample, a high proportion of HIV-positive and HIV-negative men who have sex with men have AIN. The sensitivity of cytology to detect AIN is higher for clinician-collected versus self-collected specimens and for HIV-positive versus HIV-negative men. The specificity of cytology to detect AIN is higher in HIV-negative versus HIV-positive men. However, the probability of AIN in a patient with a negative cytology result may not be low enough (23% for HIV-negative men and 45% for HIV-positive men with a patient-collected specimen) for clinicians to be comfortable recommending no anoscopy for those with a negative cytology result if done as a one-time test. These data raise the question of whether the optimal population screening strategy is cytology screening with anoscopy only for those who test positive or whether anoscopy should be recommended for everyone in these risk groups. Given limited resources and the limited number of clinicians trained in anoscopy, cytology screening may be the best current approach to identifying disease in the at-risk population.

Background: Infection with human papillomavirus (HPV) is causally linked to the development of anal and cervical cancer. In the United States, the incidence of anal cancer among men who have sex with men (MSM) is higher than the incidence of cervical cancer among women. Anal squamous intraepithelial lesions (ASILs) are anal cancer precursors comprising low-grade squamous intraepithelial lesions (LSILs) and high-grade squamous intraepithelial lesions (HSILs). The prevalence of cervical cancer precursor lesions peaks at around 30 years of age. The age-related prevalence of ASILs in HIV-negative MSM is unknown. Methods: We conducted a cross-sectional analysis of the prevalence and determinants of ASILs in 1262 HIV-negative MSM aged 18-89 years recruited from four U.S. cities. Anal cytology and behaviorai data were obtained. Anal HPV infection status was assessed by polymerase chain reaction. Independent predictors of ASILs were identified using logistic regression. All statistical tests were two-sided. Results: The prevalences of LSILs and HSILs were 15% and 5%, respectively, and did not change with age. In a multivariable analysis, the risk of LSILs was associated with having more than five male receptive anal sex partners (P = .03), any use of poppers (alkyl nitrites) in the previous 6 months [odds ratio (OR) = 1.6, 95% confidence interval (CI) = 1.1 to 2.5; P= .03] or use of injection drugs two or more times per month during the previous 6 months [OR = 19, 95% CI = 1.3 to 277; P = .03], older age at first receptive anal intercourse (P = .004), and infection with a greater number of HPV types (P

Background: Little is known in human immunodeficiency virus (HIV)-positive women about how the combination of plasma HIV RNA level and CD[4.sup.+] T-cell count is associated with the natural history of human papillomavirus (HPV) infection or about HPV reactivation--whether it occurs and with what frequency in HIV-positive women. Methods: HIV-positive (n = 1848) and -negative (n = 514) women were assessed at semiannual visits (total person-years = 5661) for cervicovaginal HPV with polymerase chain reaction assays and for squamous intraepithelial lesions (SILs) by Pap smear. We studied the prevalent detection of HPV and SILs with generalized estimating equations and the incident detection and persistence of HPV and SILs with multivariable Cox models. All statistical tests were two-sided. Results: We observed a strong interaction between the associations of CD[4.sup.+] and plasma HIV RNA strata with both prevalent ([P.sub.interaction] = .002) and incident ([P.sub.interaction] = .001) detection of HPV. Indeed, the hazard ratio for incident HPV detection peaked between 4.0 and 5.0, with either a CD[4.sup.+] count of less than 200 cells per [mm.sup.3] or an HIV RNA level of more than 100000 copies per mL. Although incident HPV detection in all women was associated with the number of recent sex partners ([P.sub.trend]

An attempt is made to determine the incidence and predictors of genital warts and vulvar intraepithelial neoplasia among women with the human immunodeficiency virus. The incidence of warts among women who are human immunodeficiency virus seronegative is 1.31 versus 5.01 per 00 person-years among women who are seropositive, whereas the incidence of vulvar intraepithelial neoplasia is 1.31 versus 4.67 per 100 person-years.

Background: The impact of highly active antiretroviral therapy (HAART) on the natural history of HPV infection and anal squamous intraepithelial lesions (SIL) in HIV-infected men who have sex with men (MSM) is poorly documented. Goal: The goal of this study was to evaluate the prevalence of anal HPV infection and SIL inpatients under HAART. Study Design: Forty-five HIV-infected protease inhibitor-experienced MSM were enrolled in a cross-sectional study. Each patient provided anal samples for anal cytology, histology, and human papillomavirus (HPV) DNA testing. Results: The patients had previously received HAART for a median of 32 months. Anal cytology was abnormal in 32 of 45 (71%) patients, including high-grade SIL in 10 patients (22%), low-grade SIL in 19 patients (42%), and atypical squamous cells of undetermined significance in 3 patients (7%). HPV DNA was detected 36/45 men (80%). The prevalence of anal SIL and HPV infection were similar in patients exhibiting a significant increase in CD4+ cell count after HAART initiation compared with those who did not. Conclusion: Our results demonstrate a high prevalence of anal SIL, including high-grade SIL, and anal HPV infection in HIV-infected MSM despite immune restoration under HAART.

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 (

Background: A few recent studies have suggested that other sexually transmitted infections may increase the likelihood of a human papillomavirus (HPV) infection progressing to high-grade cervical neoplasia and cancer. Goal: The goal was to assess whether exposures to Chlamydia trachomatis, human T-cell lymphotrophic virus type 1 (HTLV-I), and/or human simplex virus type 2 (HSV-2) are greater in colposcopy patients with cervical intraepithelial neoplasia grade 3 or cancer (CIN3+) than in patients with low-grade cervical neoplasia (CIN1). Study Design: Sequential patients (n = 447) attending a colposcopy clinic in Kingston, Jamaica, a country with high cervical cancer rates and high HTLV-I prevalence, were tested for (1) HPV DNA by L1 consensus primer (MY09/11) polymerase chain reaction assays, (2) C trachomatis DNA by ligase chain reaction, (3) C trachomatis antibodies by both microimmunofluorescence and a peptide (VS4) enzyme linked immunosorbent assay (ELISA), (4) HTLV-I antibodies by ELISA confirmed by western blotting, and (5) HSV-2 antibodies by a recombinant HSV-2-specific ELISA. Odds ratios and 95% confidence intervals were estimated with use of multinomial logistic regression models. Results: HPV DNA detection was associated with grade of cervical neoplasia but other evaluated sexually transmitted infections were not. Conclusions: HTLV-I, C trachomatis, and/or HSV-2 were not associated with severity of cervical neoplasia in Jamaican women.

Background: Anal cancer and its precursor lesion, anal squamous intraepithelial lesions (SILs), are associated with human papillomavirus (HPV) infection. Anal HPV infection and anal SIL are common in HIV-positive men who have sex with men; receptive anal intercourse is presumed to be the mode of acquisition of HPV. Objective: To assess the prevalence and risk factors for anal HPV infection and anal SIL in HIV-positive men with no history of anal intercourse. Design: Cross-sectional study. Setting: Hopital Europeen Georges Pompidou outpatient clinic, Paris, France. Patients: 118 HIV-infected men. Measurements: 50 HIV-positive heterosexual male injection drug users with no history of anal intercourse and 67 HIV-infected men who had sex with men were evaluated by using anal cytologic, anal histologic, and anal HPV DNA testing. Results: 23 of the 50 heterosexual injection drug users (46%) had anal HPV infection. Low-grade SIL (LSIL) was found in 8 patients (16%) and high-grade SIL (HSIL) in 9 patients (18%). Among the 67 men who had sex with men, anal HPV infection was found in 57 patients (85%), LSIL in 33 patients (49%), and HSIL in 12 patients (18%). In univariate analysis, risk factors for abnormal anal cytologic or histologic findings in injection drug users included CD4+ cell counts less than 250 x 10(super 6) cells/L (odds ratio, 5.7 [95% CI, 1.6 to 20.4]), plasma HIV RNA viral load greater than 1.7 log copies/mL (odds ratio, 8.9 [CI, 1.1 to 76.0]), previous AIDS-defining event (odds ratio, 4.3 [CI, 1.2 to 15.6]), and anal HPV detection (odds ratio, 5.7 [CI, 1.6 to 20.4]). Risk factors among men who had sex with men included having more than 10 lifetime receptive anal intercourse episodes (odds ratio, 5.6 [CI, 1.6 to 19.8]) and anal HPV detection (odds ratio, 8.7 [CI, 1.9 to 39.0]). Conclusions: Anal HPV infection and anal SIL may be acquired in the absence of anal intercourse in HIV-positive men. The prevalence of HSIL is high among HIV-positive injection drug users. All HIV-positive men with CD4+ cell counts less than 500 x 10(super 6) cells/L, regardless of history of anal intercourse, should be considered for anal cytologic screening; however, additional studies are needed to determine the efficacy of this procedure to prevent anal cancer in these populations.

Women infected with HIV are more likely to have an abnormal Pap smear than non-infected women. In a study of 1,713 HIV-infected women and 482 non-infected women, 38% of the HIV-infected women had an abnormal Pap smear compared to 16% of the non-infected women. However, only 2.5% of the HIV-infected women had precancerous changes. Low CD4 T cell counts, high blood viral levels, human papillomavirus infection and many sexual partners were all risk factors for an abnormal Pap smear.

HIV-positive homosexual men may be at higher risk for anal squamous intraepithelial lesions (ASIL) and possibly for anal cancer than HIV-negative homosexual men. ASIL are cellular changes that may develop into cancer. Researchers examined 346 HIV-positive and 262 HIV-negative homosexual men for evidence of anal diseases. Twenty percent of HIV-positive men developed high-grade intraepithelial lesions, compared to 8% of HIV-negative men, during the two years they were studied. Infection with human papillomavirus increased the risk of ASIL, regardless of HIV status.

HIV-positive homosexual men may be at higher risk than HIV-negative men of developing cellular changes in the anus that could lead to anal cancer. Researchers examined 346 HIV-positive and 262 HIV-negative homosexual and bisexual men for evidence of anal squamous intraepithelial lesions (ASIL). ASIL was detected in 36% of men with HIV and 7% of men without HIV infection. Anal infection with human papillomavirus and a history of receptive anal intercourse increased the risk of ASIL, regardless of HIV status. Screening of homosexual men for ASIL may prevent anal cancer.

Anal cytology may be a useful technique in the diagnosis of anal squamous intraepithelial lesions (ASIL) in gay men. ASIL are a precursor of anal squamous cell cancer in the same way that cervical squamous intraepithelial lesions (CSIL) are precursors of cervical cancer in women. Researchers used a technique similar to a Pap smear to analyze anal cells taken from 407 HIV-positive and 251 HIV-negative gay men. A positive test identified 69% of the HIV-positive men subsequently shown to have ASIL on biopsy. It was less effective in identifying HIV-negative men with ASIL.

Infection with human papillomavirus (HPV) is a risk factor for developing cervical neoplasia (tumors) that often develops into cancer. These tumors are presently screened for by the Pap smear, but this test is fairly insensitive, detecting only 50 to 80 percent of the cases of cervical neoplasia. A test that would identify those infected with HPV could be used to detect those at high risk for these tumors, who could then undergo the more time-consuming and more costly, but more accurate, colposcopy exam for these abnormalities. A test that identifies HPV DNA (hybridization) has been developed to detect infection with HPV. Studies have shown that not all infected with the virus have abnormal Pap smear results and vice versa. It is thought that a Pap smear in combination with an HPV DNA test may be most useful in determining who should be further examined by colposcopy. This study examined the association between HPV DNA results and Pap smear results to see if rescreening is useful for those that are HPV-positive. The tests were performed in 125 women. HPV results were not known by those examining the Pap smear results, two pathologists and a private cytologic laboratory. HPV DNA test results were positive for 24 subjects (19 percent). The private cytology laboratory read 6 of the 24 Pap smears from HPV-positive women as abnormal, but only 3 of 101 from HPV-negative individuals were read as abnormal. On the other hand, one pathologist read 15 of the 24 Pap smears from HPV-positive patients as abnormal, while 8 of 101 smears from HPV-negative individuals were considered atypical. A second pathologist read 11 of the 24 and 7 of the 101, respectively, as abnormal. Cervical epithelial neoplasia was diagnosed in none of the HPV-positive Pap smears by a private laboratory, in 40 percent by the first pathologist, and in 20 percent by the second. These results indicate that rescreening the Pap smear results of those who test positive for HPV-infection is useful and is likely to uncover a significant number of additional cases of cervical intraepithelial neoplasia. (Consumer Summary produced by Reliance Medical Information, Inc.)

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 [is less than] .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. [J Natl Cancer Inst 2001;93:843-9]

Background: Human papillomavirus (HPV) infection is associated with precancerous cervical squamous intraepithelial lesions commonly seen among women infected with human immunodeficiency virus-1 (HIV). We characterized HPV infection in a large cohort of HIV-positive and HIV-negative women participating in the Women's Interagency HIV Study to determine the prevalence of and risk factors for cervicovaginal HPV infection in HIV-positive women. Methods: HIV-positive (n = 1778) and HIV-negative (n = 500) women were tested at enrollment for the presence of HPV DNA in a cervicovaginal lavage specimen. Blood samples were tested for HIV antibody status, level of CD4-positive T cells, and HIV RNA load (copies/mL). An interview detailing risk factors was conducted. Univariate and multivariate analyses were performed. Results: Compared with HIV-negative women, HIV-positive women with a [CD4.sup.+] cell count of less than 200/[mm.sup.3] were at the highest risk of HPV infection, regardless of HIV RNA load (odds ratio [OR] = 10.13; 95% confidence interval [CI] = 7.32-14.04), followed by women with a [CD4.sup.+] count greater than 200/[mm.sup.3] and an HIV RNA load greater than 20 000 copies/mL (OR = 5.78; 95% CI = 4.17-8.08) and women with a [CD4.sup.+] count greater than 200/[mm.sup.3] and an HIV RNA load less than 20 000 copies/mL (OR = 3.12; 95% CI = 2.36-4.12), after adjustment for other factors. Other risk factors among HIV-positive women included racial/ethnic background (African-American versus Caucasian, OR = 1.64; 95% CI = 1.192.28), current smoking (yes versus no; OR = 1.55; 95% CI = 1.20-1.99), and younger age (age [is less than]30 years versus [is greater than or equal to]40 years; OR = 1.75; 95% CI = 1.23-2.49). Conclusions: Although the strongest risk factors of HPV infection among HIV-positive women were indicators of more advanced HIV-related disease, other factors commonly found in studies of HIV-negative women, including racial/ethnic background, current smoking, and age, were important in HIV-positive women as well. [J Natl Cancer Inst 1999;91:226-36]