Objectives Sexual gender minority (SGM) populations are at risk for human papillomavirus (HPV)–related cancers of the anogenital tract and oropharynx and often face barriers to health care. The goals of this document are to clarify language to provide inclusive care for SGM populations and to provide recommendations for screening and prevention of HPV-related cancers in SGM populations. Materials and Methods An expert committee convened by the American Society for Colposcopy and Cervical Pathology performed a narrative review of the literature through February 2023. A comprehensive MEDLINE database search was performed for relevant studies. The literature review was divided into categories by organ/topic and by SGM population. Given the variability in available data for several of the categories, recommendations were made based on national guidelines where appropriate or expert opinion where there were less data to support risk-based guidelines. Results Definitions and terminology relevant to SGM populations are presented. The authors advocate the adoption of sexual orientation gender identity data collection and an organ-based screening approach, which is possible with knowledge of patient anatomy, sexual behaviors, and clinical history. This includes screening for cervical cancer per national recommendations, as well as screening for anal, vulvar, vaginal, penile, and oral cancers based on risk factors and shared clinical decision making. The authors recommend consideration of HPV vaccination in all SGM individuals up to age 45 years old who are at risk. Conclusions An organ-based screening approach is part of a global strategy to create an inclusive care environment and mitigate barriers to screening and prevention of HPV-mediated cancers in SGM populations.

Background: This is a Phase I trial demonstrating safety and tolerability of intravaginal curcumin for future use in women with cervical neoplasia. Objective: The objective of this study was to assess the safety, tolerability, and pharmacokinetics of intravaginal curcumin in healthy women. Study design: We conducted a 3+3 dose-escalation Phase I trial in a group of women aged 18–45 years. Thirteen subjects were given one of four doses of curcumin powder (500 mg, 1,000 mg, 1,500 mg, and 2,000 mg) packed in gelatin capsules, which was administered intravaginally daily for 14 days. The primary end point for this study was safety based on severe adverse events regarding laboratory toxicity, clinical findings, and colposcopic abnormalities. We administered an acceptability questionnaire to assess product experience and attributes. Results: No dose-limiting toxicities (0/13) were experienced (95% confidence interval: 0.0%– 22.8%) in this study. The pharmacokinetics data demonstrated that curcumin and curcumin conjugates were not measurable in the serum and negligible in the urine of the study participants. Although 23 adverse events occurred during the course of the trial, all events were grade I based on the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 and were resolved by the end of the study in an average of 9 days. Fifty-six percent of the adverse events were related to the study drug, which included genital pruritus (23% of subjects), vaginal discharge (100%), vaginal dryness (15%), abnormal prothrombin (23%), and hypokalemia (8%). Conclusion: Intravaginal curcumin was well tolerated by all subjects and safe. In this Phase I trial, there were no severe adverse events observed at any of the administered dose levels. All adverse events were grade I and did not result in early termination of the study. There was no evidence of systemic absorption or significant local absorption of intravaginally administered curcumin.

BACKGROUND: From 1999 through 2009, African American women in the United States had the second highest incidence rates of cervical cancer and were more likely to die from cervical cancer than women of other races. Con Amor Aprendemos (CAA) is an intervention created to educate the Latino community to reduce their risk for cervical cancer and diseases related to human papilloma virus (HPV). CAA was adapted to With Love We Learn (WLWL) to prevent cervical cancer and HPV in African American communities. COMMUNITY CONTEXT: Health ministries of 2 churches in the Atlanta area partnered with the Spirit Foundation Inc to adapt CAA to WLWL by tailoring the curriculum to the African American faith-based community. METHODS: The National Cancer Institute's Research to Reality (R2R) mentorship program pair collaborated with program staff on an adaptation summary form, a tool to document and assist with adapting the program curriculum with fidelity. Trainers, faith leaders, and participants adapted the program in 4 phases: 1) review of the CAA curriculum, 2) a focus group discussion to determine changes for the WLWL curriculum, 3) train-the-trainer sessions on program delivery, and 4) a pilot intervention and follow-up focus group to evaluate the new curriculum. OUTCOMES: The CAA/WLWL curriculum was adapted and piloted in a faith-based setting. Adaptations to the CAA program included pictures, games, statistics on cervical cancer, dialogues, and delivery of curriculum. INTERPRETATION: Community engagement in the adaptation of WLWL through various methods was critical to tailoring an evidence-based program to a new population and setting.

Cervical cancer screening using Papanicolaou's smear test has been highly effective in reducing death from this disease. However, this test is unaffordable in low- and middle-income countries, and its complexity has limited wide-scale uptake. Alternative tests, such as visual inspection with acetic acid or Lugol's iodine and human papillomavirus DNA, are sub-optimal in terms of specificity and sensitivity, thus sensitive and affordable tests with high specificity for on-site reporting are needed. Using proteomics and bioinformatics, we have identified valosin-containing protein (VCP) as differentially expressed between normal specimens and those with cervical intra-epithelial neoplasia grade 2/3 (CIN2/CIN3+) or worse. VCP-specific immunohistochemical staining (validated by a point-of-care technology) provided sensitive (93%) and specific (88%) identification of CIN2/CIN3+ and may serve as a critical biomarker for cervical-cancer screening. Future efforts will focus on further refinements to enhance analytic sensitivity and specificity of our proposed test, as well as on prototype development.

Objective: To evaluate the natural history of treated and untreated cervical intraepithelial neoplasia-2 (CIN2) among HIV-positive women. Methods: Participants were women enrolled in the Women's Interagency HIV Study between 1994 and 2013. One hundred four HIV-positive women diagnosed with CIN2 before age 46 were selected, contributing 2076 visits over a median of 10 years (interquartile range 5-16). The outcome of interest was biopsy-confirmed CIN2 progression, defined as CIN3 or invasive cervical cancer. CIN2 treatment was abstracted from medical records. Results: Most women were African American (53%), current smokers (53%), and had a median age of 33 years at CIN2 diagnosis. Among the 104 HIV-positive women, 62 (59.6%) did not receive CIN2 treatment. Twelve HIV-positive women (11.5%) showed CIN2 progression to CIN3; none were diagnosed with cervical cancer. There was no difference in the median time to progression between CIN2-treated and CIN2-untreated HIV-positive women (2.9 vs. 2.7 years, P = 0.41). CIN2 treatment was not associated with CIN2 progression in multivariate analysis (adjusted hazard ratio 1.82; 95% confidence interval: 0.54 to 7.11), adjusting for combination antiretroviral therapy and CD4+ T-cell count. In HIV-positive women, each increase of 100 CD4+ T cells was associated with a 33% decrease in CIN2 progression (adjusted hazard ratio 0.67; 95% confidence interval: 0.47 to 0.88), adjusting for CIN2 treatment and combination antiretroviral therapy. Conclusions: CIN2 progression is uncommon in this population, regardless of CIN2 treatment. Additional studies are needed to identify factors to differentiate women at highest risk of CIN2 progression.

Background: HIV-positive women are at substantial risk of HPV-associated cervical neoplasia caused by high-risk (HR) HPVs. Methylation of the HPV genome is associated with cervical intraepithelial neoplasia grade 3 (CIN3) in HIVnegative women, yet it is unknown whether this holds true for HIV-positive women. Methods: We designed a case–control study within the Women's Interagency HIV Study (WIHS) cohort comparing HIV-positive CIN3 cases (N = 72) to HIV-positive controls without detectable CIN2þ. The unit of analysis and matching was HPV-type infection. Cases with 2HR-HPV types (N=23; 32%) had a separate control for each HR-HPV type. We developed and utilized next-generation sequencing (NGS) methylation assays for 12 different HR-HPVs, focusing on CpG sites in the L1/L2 regions. Results: Significant case–control differences in individual CpG site methylation levels were observed for multiple alpha-9 (HPV16/31/35/58) and alpha-7 HPV (HPV18/39/ 45) types, based on dichotomization of tertile levels (T3 vs. T1 and T2). Analyses combining homologous CpG sites [e. g., HPV16-L1-5608/HPV31-L1-5521/HPV35-L2L1-5570; OR = 7.28; 95% confidence interval (CI): 2.75–19.3], and (e.g., HPV18-L1-7062/HPV45-L1-7066; OR = 6.94; 95% CI: 1.23–39.3) were significant in separate case–control comparisons. In cases with multiple HR-HPVs, we tested and confirmed the hypothesis that one HR-HPV type would have higher methylation than other types detected, consistent with there being a single HR-HPV causally related to a lesion. Conclusions: CIN3 is associated with elevated L1/L2 CpG methylation levels in HIV-positive women. Impact: HPV DNA CpG methylation is a promising triage option in HIV-positive women testing positive for HR-HPV types and provides risk attribution in women with multiple HPV type infections.

Invasive cervical cancer (ICC) is the third most common female malignancy and fourth most common cause of cancer death in women globally. The risk of ICC is several-fold higher in HIV-positive women than in HIV-negative women, as are the prevalence, incidence, and persistence of oncogenic human papillomavirus (oncHPV), the infectious cause of most ICC. Although use of effective highly-active antiretroviral therapy (HAART) has been associated with reduced oncHPV prevalence and incidence and increased regression of cervical lesions, the overall incidence of ICC has not decreased in HIV-positive women during the HAART era. By increasing survival, HAART may increase lifetime oncHPV infections, allowing accumulation of somatic mutations and epigenetic changes necessary for oncogenesis. Currently, no anti-viral medications are clinically approved to treat cervical HPV infections. In vitro studies have shown that lopinavir (LPV), an HIV-1 protease inhibitor (PI) used in some HAART regimens, may have activity against oncHPV through inhibition of viral oncogene E6. Most recently, an early phase clinical trial conducted in Nairobi, Kenya studied topical application of LPV to the cervix; preliminary results showed that 21 of 23 women initially diagnosed with high-grade disease returned to normal on subsequent Papanicolaou (Pap) smears and showed visible regression of cervical lesions. We therefore assessed the hypothesis that oral LPV use may be associated with decreased prevalence and increased clearance of oncHPV compared to other antiretroviral (ARV) regimens.

Objective Anal cancer rates are increasing among HIV-infected persons. Although an efficacious human papillomavirus (HPV) vaccine is available, HPV vaccination rates remain low. Therefore, providers perform anal cancer screening, but there is no consensus on the optimal methods or timing of screening. This study was performed to determine the prevalence of and factors associated with anal squamous intraepithelial lesions in sexually active HIV-infected young men who have sex with men and transgender women. Materials and Methods We performed a single-center, retrospective study of sexually active HIV-infected young men who have sex with men and transgender women aged 13 to 24 years at an HIV clinic in Atlanta GA from 2009 to 2016. We used analysis of variance and χ2 tests of independence to evaluate bivariate associations and identify demographic, behavioral, and clinical risk factors. Results Of 314 subjects with a mean (SD) age of 20.4 (2.1) years at initial anal cytology testing, 5% had completed the HPV vaccine series at or before the time that cytology was obtained. Ninety-five percent of the anal cytology tests obtained were abnormal, and 72 (29%) of those subjects returned for diagnostic testing either by intraoperative biopsy or high-resolution anoscopy. Fifty-seven percent of those who underwent biopsy had histologic high-grade squamous intraepithelial lesions including 2 cases of carcinoma in situ. A history of greater than 20 lifetime sexual partners was associated with abnormal histology (probability < 0.001, p =.017). Conclusions Our study highlights the value of early, standardized screening to avoid missing anal dysplasia or cancer, particularly in unvaccinated persons with high numbers of sexual partners.

Objectives: Women living with HIV (WLWH) have a greater risk of anal cancer than women without HIV; however, there are limited studies that examine awareness of anal cancer risk among WLWH and "high-risk"HIV-negative women. This study examines risk factors for anal cancer, perceptions of risk for anal cancer, and perceptions of anal cancer screening among a cohort of WLWH and high-risk HIV-negative women. Materials and Methods: From the Atlanta, GA, and Bronx, NY, sites of the Women's Interagency HIV Study, 155 WLWH and HIV-negative women were enrolled and the Champion Health Belief Model Scale questionnaire measuring risk perceptions to anal cancer was administered to each participant. Results: The WLWH perceived anal cancer to be less serious and perceived facing fewer barriers to anal cancer screening than HIV-negative women (both p =.01). Older women (≥50 years) felt that they had less barriers to anal cancer screening (p =.047). Moreover, women who had less than a high school education felt more susceptible to anal cancer (p =.001), as did women who reported a history of anal intercourse (p =.017). Conclusions: Despite being at an increased risk for anal cancer, perceptions of susceptibility to anal cancer and seriousness of anal cancer were low among WLWH. These findings highlight opportunities for provider and patient educational interventions to improve awareness of anal cancer risk among WLWH.

Over the past two decades, anti-vaccine activism in the USA has evolved from a fringe subculture into an increasingly well organised, networked movement with important repercussions for public health. The COVID-19 pandemic has exacerbated this evolution and magnified the reach of vaccine misinformation. Anti-vaccine activists, who for many years spoke primarily to niche communities hesitant about childhood vaccinations, have used traditional and social media to amplify vaccine-related mistruths about COVID-19 vaccines while also targeting historically marginalised racial and ethnic communities. These efforts contributed to COVID-19 vaccine hesitancy and expanded the movement, with early indications suggesting that this hesitancy could now also be increasing hesitancy that existed pre-pandemic towards other vaccines. It is important to understand the implications of this recent evolution of anti-vaccine activism on vaccination uptake and the promotion of sound public health strategies. In this Viewpoint, we summarise the latest developments in US-based anti-vaccine activism and propose strategies for confronting them.