Construct validity and responsiveness of a health-related symptom index for persons either treated or monitored for anal high-grade squamous intraepithelial lesions (HSIL): AMC-A01/-A03.

PURPOSE: To determine whether treatment of anal high-grade squamous intraepithelial lesions (HSIL), vs active monitoring, is effective in reducing incidence of anal cancer in persons living with HIV, the US National Cancer Institute funded the Phase III ANal Cancer/HSIL Outcomes Research (ANCHOR) clinical trial. As no established patient-reported outcomes (PRO) tool exists for persons with anal HSIL, we sought to estimate the construct validity and responsiveness of the ANCHOR Health-Related Symptom Index (A-HRSI). METHODS: The construct validity phase enrolled ANCHOR participants who were within two weeks of randomization to complete A-HRSI and legacy PRO questionnaires at a single time point. The responsiveness phase enrolled a separate cohort of ANCHOR participants who were not yet randomized to complete A-HRSI at three time points: prior to randomization (T1), 14-70 (T2), and 71-112 (T3) days following randomization. RESULTS: Confirmatory factor analysis techniques established a three-factor model (i.e., physical symptoms, impact on physical functioning, impact on psychological functioning), with moderate evidence of convergent validity and strong evidence of discriminant validity in the construct validity phase (n = 303). We observed a significant moderate effect for changes in A-HRSI impact on physical functioning (standardized response mean = 0.52) and psychological symptoms (standardized response mean = 0.60) from T2 (n = 86) to T3 (n = 92), providing evidence of responsiveness. CONCLUSION: A-HRSI is a brief PRO index that captures health-related symptoms and impacts related to anal HSIL. This instrument may have broad applicability in other contexts assessing individuals with anal HSIL, which may ultimately help improve clinical care and assist providers and patients with medical decision-making.

Linguistic validation of the Spanish version of the Anal Cancer High-Grade squamous intraepithelial lesions outcomes Research Health-Related Symptom Index (A-HRSI): AMC-A04.

OBJECTIVES: The Anal Cancer High-grade squamous intraepithelial lesions (HSIL) Outcomes Research (ANCHOR) Health-Related Symptom Index (A-HRSI) is a 25-item measure that assesses physical symptoms and impacts, and psychological symptoms. To promote generalizability and equity in the capture of these concepts in Spanish-speaking participants, we linguistically validated a Spanish version of A-HRSI. METHODS: Following independent forward translation and reconciliation of A-HRSI from English to Spanish, two rounds of cognitive interviews were completed with ANCHOR participants who had been diagnosed with anal HSIL in the prior nine months and preferred delivery of their healthcare in Spanish. Interviews were coded to highlight any items and concepts that were reported as being difficult for any reason by ≥ 3 participants, with such items revised during a research team panel discussion and tested in a second round of interviews if applicable. RESULTS: Seventeen participants representing 8 nationalities were enrolled (Round 1 n=10, Round 2 n=7); 7 participants reported not completing high school (41.2%). No difficulties were reported with respect to the theoretical concepts measured by A-HRSI. We made modifications to the Spanish translation of eight items and two response option terms in cases where participants had difficulty understanding a term, experienced problems in discriminating between terms, or preferred the use of an alternative term to represent the concept(s). CONCLUSION: The Spanish version of A-HRSI is a linguistically valid tool that can be used to assess physical symptoms, impacts, and psychological symptoms related to anal HSIL. Language is a tremendous barrier to enrolling patients to clinical trials. The anal cancer high-grade squamous intraepithelial lesions (HSIL) outcomes research [ANCHOR] trial is a randomized clinical trial that recently established that the treatment of anal HSIL, versus active monitoring, is effective in reducing incidence of anal cancer in persons living with HIV (PLWH). The ANCHOR Health-Related Symptom Index (A-HRSI) is a 25-item patient-reported outcomes measure that was developed to assess physical symptoms, physical impacts, and psychological symptoms related to anal HSIL. As approximately 10% of ANCHOR participants preferred the delivery of their healthcare in Spanish, the purpose of the present study was to linguistically validate a Spanish version of A-HRSI. Based on feedback from interviews with 17 participants from the ANCHOR trial who had been diagnosed with anal HSIL in the prior nine months and preferred delivery of their healthcare in Spanish, we made modifications to the Spanish translation of eight items and two response option terms in cases where participants had difficulty understanding a term, experienced problems in discriminating between terms, or preferred the use of an alternative term to represent the concept(s). The Spanish version of A-HRSI is a linguistically valid tool that can be used to assess physical symptoms, impacts, and psychological symptoms related to anal HSIL as part of clinical trials or routine care.

Treatment of Anal High-Grade Squamous Intraepithelial Lesions to Prevent Anal Cancer.

BACKGROUND: The incidence of anal cancer is substantially higher among persons living with the human immunodeficiency virus (HIV) than in the general population. Similar to cervical cancer, anal cancer is preceded by high-grade squamous intraepithelial lesions (HSILs). Treatment for cervical HSIL reduces progression to cervical cancer; however, data from prospective studies of treatment for anal HSIL to prevent anal cancer are lacking. METHODS: We conducted a phase 3 trial at 25 U.S. sites. Persons living with HIV who were 35 years of age or older and who had biopsy-proven anal HSIL were randomly assigned, in a 1:1 ratio, to receive either HSIL treatment or active monitoring without treatment. Treatment included office-based ablative procedures, ablation or excision under anesthesia, or the administration of topical fluorouracil or imiquimod. The primary outcome was progression to anal cancer in a time-to-event analysis. Participants in the treatment group were treated until HSIL was completely resolved. All the participants underwent high-resolution anoscopy at least every 6 months; biopsy was also performed for suspected ongoing HSIL in the treatment group, annually in the active-monitoring group, or any time there was concern for cancer. RESULTS: Of 4459 participants who underwent randomization, 4446 (99.7%) were included in the analysis of the time to progression to cancer. With a median follow-up of 25.8 months, 9 cases were diagnosed in the treatment group (173 per 100,000 person-years; 95% confidence interval [CI], 90 to 332) and 21 cases in the active-monitoring group (402 per 100,000 person-years; 95% CI, 262 to 616). The rate of progression to anal cancer was lower in the treatment group than in the active-monitoring group by 57% (95% CI, 6 to 80; P = 0.03 by log-rank test). CONCLUSIONS: Among participants with biopsy-proven anal HSIL, the risk of anal cancer was significantly lower with treatment for anal HSIL than with active monitoring. (Funded by the National Cancer Institute; ClinicalTrials.gov number, NCT02135419.).

Risk Factors for Anal Dysplasia in Transgender Women: A Retrospective Chart Review.

OBJECTIVE: The aim of the study was to assess risk factors for anal human papillomavirus (HPV) infection and anal dysplasia among a cohort of transgender women (TGW). METHODS: A retrospective chart review was conducted based on electronic medical records of TGW patients seen in the University of Miami Health System between 2010 and 2016. Outcome measures included risk factors of anal dysplasia, including HIV infection, receptive anal intercourse, and smoking history. Descriptive statistical analysis and χ testing were used. RESULTS: Sixty-nine TGW patients' charts were reviewed. Patients' ages ranged from 18 to 72 (mean = 38 [15]). Twenty-two (30%) were older than 50 years; 10 (15%) were black/African descent; 20 (29%) reported a smoking history; 6 (9%) were HIV positive, and 28 (72%) among those with known partner preference (n = 39) reported male partners. Male partner preference was significantly associated with being black/African descent (p = .009) and being single (p = .048). Older age was significantly associated with HIV-positive status (p = .023). The average number of risk factors per person was 2.10 (0.97). Sixty-one years or older had the highest average number of risk factors (2.90 [0.88]). CONCLUSIONS: Because rates of HIV, dangerous sexual behaviors, and other risk factors for anal dysplasia continue to persist among TGW, this study reinforces the need to increase the focus on anal health in the care of TGW and the need for further research to guide patient care and anal dysplasia screening strategies among those individuals.

Exploring the Perceptions of Anal Cancer Screening and Behaviors Among Gay and Bisexual Men Infected With HIV.

BACKGROUND: The incidence of anal cancer is on the rise among HIV-infected men who have sex with men (MSM). Given the increasing availability of screening, this study explored anal cancer screening awareness and behaviors among MSM infected with HIV. METHODS: In-depth interviews were conducted with 58 MSM infected with HIV. RESULTS: Other than 2 participants treated for anal cancer and 3 treated for precancerous anal lesions, the majority of participants had never heard of anal cancer. Men reported lack of awareness and recommendations from their health care professionals as the greatest barriers to screening. Upon learning about their risk for anal cancer and the availability of screening, the men were eager to discuss screening with their physicians. Participants provided numerous recommendations for future interventions, including training health care professionals to promote screening, disseminating information pertaining to anal cancer through social networks, and creating media campaigns to raise awareness about the need to screen for this type of cancer. CONCLUSIONS: Future intervention work should focus on ensuring that health care professionals, particularly among HIV/primary care specialists, promote screening for anal dysplasia. It is critical that intervention methods use a community-based approach to raise awareness about the need to screen for anal cancer, especially among MSM infected with HIV.

HPV in HIV-Infected Women: Implications for Primary Prevention.

BACKGROUND: There is growing evidence that human immunodeficiency virus (HIV)-infected women might have a different human papillomavirus (HPV) type distribution in cervical dysplasia specimens as compared to the general population. This has implications for primary prevention. OBJECTIVE: We aimed to obtain preliminary data on the HPV genotypes prevalent in histological samples of HIV-infected women with cervical intraepithelial neoplasia (CIN) 3/CIS of the cervix in Miami, FL, USA. METHODS: Retrospective data were collected on HIV-infected women referred to the University of Miami-Jackson Memorial Hospital colposcopy clinic between years 2000 and 2008. The histology slides of CIN 3/CIS biopsies underwent pathological review and sections were cut from these archived specimens for HPV DNA extraction. HPV genotyping was then performed using the GeneSquare™ HPV genotyping assay. We report on our first set of 23 samples. RESULTS: Eight high-risk HPV types were detected. Types in decreasing order of frequency were 16, 35, 45, 52, 59, 31, 58, and 56. Most cases had multiple infections. HPV type 16 was the most common (45%) followed by HPV-35 and -45 with equal frequency (40%). No samples contained HPV-18. CONCLUSION: Our preliminary results suggest that cervical dysplasia specimens of HIV-infected women more likely (55%) contain non-16 and -18 high-risk HPV types. We show that this held true for histologically confirmed severe dysplasia and carcinoma-in situ. Epidemiological studies guide vaccine development, therefore HPV type prevalence in CIS and invasive cervical cancer among HIV-infected women should be more rigorously explored to ensure that this highly vulnerable population receives appropriate primary prevention.

Human papillomavirus awareness among HIV-infected drug users in two urban areas.

Human papillomavirus (HPV) is the cause of cervical and anal cancer. Human immunodeficiency virus (HIV) infection and cocaine use are associated with increased risk for HPV infection and associated diseases, but little is known about HIV-infected drug users' awareness of HPV. We investigate HPV awareness among HIV-infected, sexually-active crack cocaine users from two inner-city hospitals in Florida and Georgia during their inpatient stays. Multivariate logistic regression analysis was used to examine potential correlates of HPV awareness. We interviewed 215 participants (110 women; 105 men) about their awareness of HPV infection. Overall, only 25% of respondents reported having heard of HPV. The odds of having heard of HPV were greater for respondents having a high-school degree or higher, having ever gone to an HIV provider for HIV care, and having two or more sexual partners. Despite increased susceptibility to HPV infection and HPV-related cancers, our study findings suggest that sexually-active HIV-infected crack cocaine users have little awareness of HPV and highlight the need for programmes targeting HPV education for HIV-infected crack cocaine drug users.

Clinical and epidemiological characteristics of individuals with very high rapid plasma reagin.

The objective of the study was to identify clinical and epidemiological characteristics of patients with infectious syphilis who presented with a high rapid plasma reagin (RPR) titre (≥1: 512) during the year of 2009 at the Miami Dade County Health Department (MDCHD) STD clinic. Potential cases were identified by a search in the electronic database. Among 519 individuals identified with reactive RPR, 190 individuals met criteria for infectious syphilis and 32 of them had at least one RPR titre of ≥1: 512. We found that the majority of individuals with high RPR were men who have sex with men (82%), from ethnic minorities (91%), and HIV infected (75%) but only 3 of them were on antiretroviral therapy. Overall, 50% of these patients with very high RPR titres were symptomatic, and the most common symptom was skin rash (93%).

Increase in lymphogranuloma venereum cases in South Florida.

The purpose of the study was to evaluate the clinic prevalence and clinical characteristics of patients with LGV since 2007 when active clinic surveillance started. We review all the reports of rectal Chlamydia trachomatis and LGV testing of those samples. Chlamydia trachomatis LGV DNA was detected by Nucleic Acid Amplification/ompA gene sequencing. Medical records of all patients with LGV were reviewed. Prevalence of rectal CT among tested individuals was relatively stable during the study period: 2007 (15%), 2008 (15%), 2009 (12%) and 2010 (14%). Eight cases of LGV were identified during the study period, one in 2009 and seven in 2010. All individuals were male and all except one had sex with only men. Most of them were also infected with HIV (62.5%). We concluded that this is the first report of LGV cases in South Florida and shows a rapid increase in the number of cases in the last year.

Description of a pilot anal pap smear screening program among individuals attending a Veteran's Affairs HIV clinic.

Despite the higher risk of anal cancer among HIV-infected individuals currently there are no national or international guidelines for anal dysplasia screening. We assessed acceptance and feasibility of screening for anal intraepithelial neoplasia (AIN), the rate of abnormalities, and relationship between the presence of AIN and a history of receptive anal intercourse. Eighty-two percent of HIV-patients approached during routine clinic visit agreed to participate in the study with anal Pap smear collection; 53% had abnormal cytology results and among those undergoing high-resolution anoscopy with biopsy, 55% had high-grade AIN, including 2 cases of carcinoma in situ. Anal cytology was well accepted and it was feasible to be incorporated into HIV primary care practice. Abnormal cytology was not significantly associated with history of anal intercourse (p = 0.767). The high rate of abnormal results reinforces the need for further evaluation of the role of systematic anal Pap smear screening for HIV patients.

Addressing anal health in the HIV primary care setting: a disappointing reality.

The increased risk of anal cancer among individuals living with HIV suggests that anal health (e.g., anal symptoms, anal practices, examination of the anus) should be an issue of priority for HIV care providers to discuss with their HIV-infected patients. We investigated the prevalence of HIV-infected individuals discussing anal health with their HIV primary care provider and factors associated with this discussion. We surveyed 518 adult patients from 5 HIV primary care clinics in Miami, Florida, from May 2004 to May 2005. Overall, only 22% of women, 32% of heterosexual men, and 54% of men who have sex with men (MSM) reported discussing anal health with their HIV providers in the prior 12 months. In a multivariable logistic regression, when adjusting for other factors, heterosexual men and MSM were 2.31 and 5.56 times, respectively, more likely to discuss anal health with their HIV providers compared to their women counterparts. Other factors associated with anal health discussion were the patients' better perception of engagement with HIV providers and having had a sexually transmitted disease exam in the past 12 months. Reporting of unprotected sex with HIV-negative or unknown HIV status was inversely related to discussion of anal health with primary care providers (odds ratio [OR] = 0.53). Efforts are greatly needed to increase the focus on anal health in the HIV primary care setting for both men and women.