Search

PURPOSE Squamous cell carcinoma of the anus (SCCA) incidence and mortality rates are rising in the United States. Understanding state-level incidence and mortality patterns and associations with smoking and AIDS prevalence (key risk factors) could help unravel disparities and provide etiologic clues. METHODS Using the US Cancer Statistics and the National Center for Health Statistics data sets, we estimated state-level SCCA incidence and mortality rates. Rate ratios (RRs) were calculated to compare incidence and mortality in 2014-2018 versus 2001-2005. The correlations between SCCA incidence with current smoking (from the Behavioral Risk Factor Surveillance System) and AIDS (from the HIV Surveillance system) prevalence were evaluated using Spearman's rank correlation coefficient. RESULTS Nationally, SCCA incidence and mortality rates (per 100,000) increased among men (incidence, 2.29-3.36, mortality, 0.46-0.74) and women (incidence, 3.88-6.30, mortality, 0.65-1.02) age ≥ 50 years, but decreased among men age < 50 years and were stable among similar-aged women. In state-level analysis, a marked increase in incidence (≥ 1.5-fold for men and ≥ two-fold for women) and mortality (≥ two-fold) for persons age ≥ 50 years was largely concentrated in the Midwestern and Southeastern states. State-level SCCA incidence rates in recent years (2014-2018) among men were correlated ( r = 0.47, P < .001) with state-level AIDS prevalence patterns. For women, a correlation was observed between state-level SCCA incidence rates and smoking prevalence ( r = 0.49, P < .001). CONCLUSION During 2001-2005 to 2014-2018, SCCA incidence and mortality nearly doubled among men and women age ≥ 50 years living in Midwest and Southeast. State variation in AIDS and smoking patterns may explain variation in SCCA incidence. Improved and targeted prevention is needed to combat the rise in SCCA incidence and mitigate magnifying geographic disparities. [Media: see text]

Background:High-risk human papillomavirus (HR-HPV) infection is a risk factor for anal cancer, yet no anal cancer screening guidelines exist for women with lower genital tract HPV-related disease. We sought to describe the prevalence of anal HR-HPV or cytologic abnormalities in such women.Methods:This cross-sectional study was performed between October 2018 and December 2021. Inclusion criteria were ≥21 years of age and a prior diagnosis of high-grade dysplasia/cancer of the cervix, vagina, or vulva. Participants underwent anal cytology and anal/cervicovaginal HR-HPV testing. Women with abnormal anal cytology were referred for high-resolution anoscopy (HRA).Results:324 evaluable women were enrolled. Primary diagnosis was high-grade dysplasia/cancer of the cervix (77%), vagina (9%), and vulva (14%). Anal HR-HPV was detected in 92 patients (28%) and included HPV-16 in 24 (26%), HPV-18 in 6 (7%), and other HR-HPV types in 72 (78%) patients. Anal cytology was abnormal in 70 patients (23%) and included atypical squamous cells of undetermined significance (80%), low-grade squamous intraepithelial lesion (9%), high-grade intraepithelial lesion (HSIL; 1%), and atypical squamous cells-cannot rule out HSIL (10%). Of these patients, 55 (79%) underwent HRA. Anal biopsies were performed in 14 patients: 2 patients had anal intraepithelial neoplasia (AIN) 2/3, 1 patient had AIN 1, and 11 patients had negative biopsies. Both patients with AIN 2/3 had a history of cervical dysplasia.Conclusions:Our results suggest an elevated risk of anal HR-HPV infection and cytologic abnormalities in women with lower genital tract dysplasia/cancer.Impact:These results add to the growing body of evidence suggesting the need for evaluation of screening methods for anal dysplasia/cancer in this patient population to inform evidence-based screening recommendations.

Supplementary Table from A Cross-Sectional Study of the Prevalence of Anal Dysplasia among Women with High-Grade Cervical, Vaginal, and Vulvar Dysplasia or Cancer: The PANDA Study

PURPOSE Compared with people living without HIV (PWOH), people living with HIV (PWH) and cancer have traditionally been excluded from immune checkpoint inhibitor (ICI) trials. Furthermore, there is a paucity of real-world data on the use of ICIs in PWH and cancer. METHODS This retrospective study included PWH treated with anti–PD-1- or anti–PD-L1-based therapies for advanced cancers. Kaplan-Meier method was used to estimate overall survival (OS) and progression-free survival (PFS). Objective response rates (ORRs) were measured per RECIST 1.1 or other tumor-specific criteria, whenever feasible. Restricted mean survival time (RMST) was used to compare OS and PFS between matched PWH and PWOH with metastatic NSCLC (mNSCLC). RESULTS Among 390 PWH, median age was 58 years, 85% (n = 331) were males, 36% (n = 138) were Black; 70% (n = 274) received anti–PD-1/anti–PD-L1 monotherapy. Most common cancers were NSCLC (28%, n = 111), hepatocellular carcinoma ([HCC]; 11%, n = 44), and head and neck squamous cell carcinoma (HNSCC; 10%, n = 39). Seventy percent (152/216) had CD4+ T cell counts ≥200 cells/µL, and 94% (179/190) had HIV viral load CONCLUSION Among PWH, ICIs demonstrated differential activity across cancer types with no excess toxicity. Safety and activity of ICIs were similar between matched cohorts of PWH and PWOH with mNSCLC.

Background African countries are underrepresented in cancer research, partly because of a lack of structured curricula on clinical research during medical education. To address this need, the MD Anderson and Zambia Virtual Clinical Research Training Program (MOZART) was developed jointly by MD Anderson Cancer Center (MDA) and the Cancer Diseases Hospital in Zambia (CDH) for Zambian clinical oncology trainees. We explored participant perspectives to provide insight for implementation of similar efforts. Materials and Methods The MD Anderson and Zambia Virtual Clinical Research Training Program consisted of weekly virtual lectures and support of Zambian-led research protocols through longitudinal mentorship groups that included CDH faculty and MDA peer and faculty mentors. Participants were contacted via email to take part in semi-structured interviews, which were conducted via teleconference and audio-recorded, transcribed, and coded. Emergent themes were extracted and are presented with representative verbatim quotations. Results Thirteen of the 14 (93%) trainees were interviewed. Emergent themes included (1) participants having diverse educational backgrounds but limited exposure to clinical research, (2) importance of cancer research specific to a resource-constrained setting, (3) complementary roles of peer mentors and local and international faculty mentors, (4) positive impact on clinical research skills but importance of a longitudinal program and early exposure to clinical research, and (5) challenges with executing research protocols. Conclusion To our knowledge, this is the first qualitative study of African clinical oncology trainees participating in a virtual clinical research training program. The lessons learned from semi-structured interviews with participants in MOZART provided valuable insights that can inform the development of similar clinical research training efforts and scale-up.

Background Disparities in mortality in human immunodeficiency virus (HIV)–associated Kaposi sarcoma have been described, particularly in Black men in the southern United States. It is unclear if there are racial/ethnic differences in the seroprevalence of Kaposi sarcoma–associated herpesvirus (KSHV) that may be contributing. Methods This is a cross-sectional study of men who have sex with men (MSM) and transgender women with HIV. Participants were recruited from an outpatient HIV clinic in Dallas, Texas, for a 1-time study visit and were excluded from analysis if they had any history of KSHV disease. Plasma was tested for antibodies to KSHV K8.1 or ORF73 antigens, and KSHV DNA was measured in oral fluids and blood by polymerase chain reaction. KSHV seroprevalence and viral shedding in blood and oral fluids were calculated. Additionally, independent risk factors for KSHV seropositivity were assessed by multivariable logistic regression analysis. Results Two hundred five participants were included in our analysis. Overall, KSHV seroprevalence was high (68%) with no significant difference between racial/ethnic groups. Among seropositive participants, KSHV DNA was detected in 28.6% of oral fluids and 10.9% of peripheral blood specimens, respectively. The factors most strongly associated with KSHV seropositivity were oral–anal sex (odds ratio [OR], 3.02), oral–penile sex (OR, 4.63), and methamphetamine use (OR, 4.67). Conclusions High local seroprevalence of KSHV is likely a key driver of the high burden of KSHV-associated diseases regionally, though it does not explain the observed disparities in KSHV-associated disease prevalence among racial/ethnic groups. Our findings support that KSHV is primarily transmitted via exchange of oral fluids.

More than 80% of global hepatocellular carcinoma (HCC) patients are estimated to occur in sub-Saharan Africa (SSA) and Eastern Asia. The most common risk factor of HCC in SSA is chronic hepatitis B virus (HBV) infection, with the incidence highest in West Africa. HBV is highly endemic in SSA and is perpetuated by incomplete adherence to birth dose immunization, lack of longitudinal follow-up care, and impaired access to antiviral therapy. HBV may directly cause HCC through somatic genetic alterations or indirectly through altered liver function and liver cirrhosis. Other risk factors of HCC in SSA include aflatoxins and, to a lesser extent, African iron overload. HIV plus HBV co-infection increases the risk of developing HCC and is increasingly becoming more common because of improving the survival of patients with HIV infection. Compared with the rest of the world, patients with HCC in SSA have the lowest survival. This is partly due to the late presentation of HCC with advanced symptomatic disease as a result of underdeveloped surveillance practices. Moreover, access to care and resource limitations further limit outcomes for the patients who receive a diagnosis in SSA. There is a need for multipronged strategies to decrease the incidence of HCC and improve its outcomes in SSA.

The aim of the study was to identify prevalence of tobacco use and associated correlates in a cohort of 332 transgender veterans who served in Iraq and Afghanistan. We identified tobacco use, nicotine replacement therapies (NRTs), and clinical comorbidities from veteran medical record databases. We compared differences in use and clinical comorbidities, using nonparametric bivariate analyses. Approximately 67% of veterans were using tobacco, with 25% receiving NRTs. Major depressive disorder, alcohol-use disorders, and drug-use disorders were significantly higher in transgender women tobacco users than in nonusers. Results emphasize future research and clinical intervention necessary to address these health conditions in this vulnerable subgroup.

Despite the overall national decline in Kaposi sarcoma (KS) incidence in the United States among persons living with HIV, previous studies suggest there might be specific subgroups of the US population that are associated with higher KS incidence rates than others. Using the 2001-2018 National Program of Cancer Registries and Surveillance, Epidemiology, and End Results Program database, we assessed KS incidence trends among young men aged 20-34 years by race and ethnicity and geographic region. Statistical significance is 2-sided. The KS incidence rate increased nationally by 1.5% per year in non-Hispanic Black men, whereas the rate decreased statistically significantly by 3.5% per year in non-Hispanic White men. A statistically significant 3.3% per year increase among young non-Hispanic Black men in the South and no change among those living in non-South regions were observed. Targeted HIV prevention and treatment in young non-Hispanic Black men in the South and further research addressing the increased KS incidence and burden in this vulnerable population are needed.

A history of gout, arthritis due to hyperuricemia, has been associated with decreased risk for neurodegenerative diseases such as Parkinson’s disease. We performed a population-based case-control study in the US Department of Veterans Affairs (VA) medical centers nationwide to assess if gout or hyperuricemia is similarly associated with the ocular neurodegenerative condition glaucoma. We used ICD-9 codes to identify a nationwide cohort of patients examined at VA healthcare eye clinics between 2000 and 2015 with a diagnosis of open-angle glaucoma (OAG) or of glaucoma suspect. We used incidence density matching to choose controls. We used multivariable logistic regression to examine associations between a history of gout and uric acid (UA) levels on relative risk of OAG or glaucoma suspect. There were 1,144,428 OAG or glaucoma suspect cases and 1,144,428 matched controls. Veterans with a history of gout had a small significant decreased risk of OAG compared to controls (ORadjusted(adj) = 0.985, 95% CI: 0.974–0.996). Treated gout was similarly associated with small decreased risk (ORadj = 0.963, 95% CI: 0.950–0.976). A small subset of patients (11.9% of cases and 13.2% of controls) had UA labs available; veterans with the highest median UA levels (> 7.29 mg/dL) did not have statistically significant differences in relative OAG risk (ORadj = 1.014, 95% CI: 0.991–1.036). Prospective research in other cohorts is needed to confirm our findings in veterans suggesting a history of gout is associated with a small decreased relative risk of glaucoma.

BackgroundThe incidence of anal squamous cell carcinoma has been increasing, particularly in people living with HIV (PLWH). There is concern that radiosensitizing drugs, such as protease inhibitors, commonly used in the management of HIV, may increase toxicities in patients undergoing chemoradiation. This study examines treatment outcomes and toxicities in PLWH managed with and without protease inhibitors who are receiving chemoradiation for anal cancer.MethodsPatient demographic, HIV management, and cancer treatment information were extracted from multiple Veterans Affairs databases. Patients were also manually chart reviewed. Among PLWH undergoing chemoradiation for anal carcinoma, therapy outcomes and toxicities were compared between those treated with and without protease inhibitors at time of cancer treatment. Statistical analysis was performed using chi-square, Cox regression analysis, and logistic regression.ResultsA total of 219 PLWH taking anti-retroviral therapy undergoing chemoradiation for anal cancer were identified and included in the final analysis. The use of protease inhibitors was not associated with any survival outcome including colostomy-free survival, progression-free survival, or overall survival (all adjusted hazard ratiop-values> 0.05). Regarding toxicity, protease inhibitor use was not associated with an increased odds of hospitalizations or non-hematologic toxicities; however, protease inhibitor use was associated with increased hospitalizations for hematologic toxicities, including febrile neutropenia (p ConclusionThe use of protease inhibitors during chemoradiation for anal carcinoma was not associated with any clinical outcome or increase in non-hematologic toxicity. Their use was associated with increased hospitalizations for hematologic toxicities. Further prospective research is needed to evaluate the safety and efficacy of protease inhibitors for patients undergoing chemoradiation.

Background Immune markers have been correlated with prognosis in a variety of solid tumors, including cervical cancer. Objective To review the literature on hematologic and immune markers and their association with recurrence and survival among patients with cervical cancer treated with chemoradiation. Evidence review This systematic review was conducted in accordance with PRISMA guidelines via searches of Ovid MEDLINE, Ovid Embase, and the Cochrane Library using keywords regarding cervical cancer, immune markers, and HIV. Studies involving patients treated with cisplatin‐based chemoradiotherapy were selected and reviewed by at least two independent reviewers, with disagreements resolved by a third reviewer. Findings A total of 737 studies were identified, of which 314 assessed immune biomarkers in immunocompetent patients (30 included in the final analysis) and 327 studies in immunosuppressed patients (5 included in the final analysis). The strongest prognostic indicators were lymphopenia and elevated neutrophil‐to‐lymphocyte ratio. Other potential markers included HPV‐specific lymphocyte response, cytokine profile, expression of immune‐blocking antigens on cell surfaces, and tumor‐associated lymphocyte, macrophage, and neutrophil infiltration. Studies of immunosuppressed patients described more severe cytopenic changes overall and concluded that viral suppression led to improved outcomes. Conclusions The immunologic interplay at work in cervical cancer development, progression, and treatment is complex. Strong evidence was found in favor of lymphopenia and elevated neutrophil‐to‐lymphocyte ratio being prognostic for worse outcomes with other markers showing potential associations as well. Although the interpretation of immune status with regard to treatment approach remains unclear, future studies should aim to tailor treatment that minimizes possible detrimental immune effects., Immune markers have been correlated with prognosis in a variety of solid tumors, including cervical cancer. In this systematic review of immune markers for cervical cancer patients being treated with chemoradiation, we surveyed the literature for immunologic and hematologic prognostic markers and found the strongest negative prognostic indicators were lymphopenia and elevated neutrophil‐to‐lymphocyte ratio.

Persons living with HIV/AIDS have a higher incidence of virus-related and tobacco/alcohol-related cancers. This study is the first to estimate the effect of HIV versus HIV-negative veterans on the risk of head and neck squamous cell carcinoma incidence in a large retrospective cohort study.The authors constructed a retrospective cohort study using patient data from 1999 to 2016 from the National Veterans Administration Corporate Data Warehouse and the VA Central Cancer Registry. This cohort study included 45,052 veterans living with HIV/AIDS and 162,486 HIV-negative patients matched by age, sex, and index visit (i.e., HIV diagnosis date or clinic visit date). The age-standardized incidence rates and estimated adjusted hazard ratios were calculated with a Cox proportional hazards regression for oropharyngeal and nonoropharyngeal head and neck cancer squamous cell carcinoma (HNSCC). The authors also abstracted human papillomavirus (HPV) status from oropharyngeal HNSCC diagnosed after 2010.Veterans living with HIV/AIDS (VLWH) have 1.71 (95% confidence interval [CI], 1.36, 2.14) times the risk of oropharyngeal cancer and 2.06 (95% CI, 1.76, 2.42) times the hazard of nonoropharyngeal cancer compared with HIV-negative veterans. VLWH with oropharyngeal squamous cell carcinoma (OPSCC) were more likely to be HPV-positive (N = 30 [81.1%]) than the HIV-negative veterans with OPSCC (N = 50 [67.6%]), although this difference was not significant (p = .135). For nonoropharyngeal cancer, the increased risk of oral cavity cancer among VLWH drove the increased risk.The study results suggest that HIV may play a role in virally mediated and nonvirally mediated HNSCC. As the HIV prevalence rises in the United States due to better survival and the incidence of HPV-positive oropharyngeal HNSCC increases, the interaction between HPV and HIV becomes increasingly relevant.

Summary Objectives To assess the methodologies used in the estimation of diagnostic accuracy of SARS-CoV-2 real-time reverse transcription polymerase chain reaction (rRT-PCR) and other nucleic acid amplification tests (NAATs) and to evaluate the quality and reliability of the studies employing those methods. Methods We conducted a systematic search of English-language articles published December 31, 2019-June 19, 2020. Studies of any design that performed tests on ≥10 patients and reported or inferred correlative statistics were included. Studies were evaluated using elements of the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) guidelines. Results We conducted a narrative and tabular synthesis of studies organized by their reference standard strategy or comparative agreement method, resulting in six categorizations. Critical study details were frequently unreported, including the mechanism for patient/sample selection and researcher blinding to results, which lead to concern for bias. Conclusions Current studies estimating test performance characteristics have imperfect study design and statistical methods for the estimation of test performance characteristics of SARS-CoV-2 tests. The included studies employ heterogeneous methods and overall have an increased risk of bias. Employing standardized guidelines for study designs and statistical methods will improve the process for developing and validating rRT-PCR and NAAT for the diagnosis of COVID-19.

Background People living with HIV/AIDS (PLWH) have an excess risk for head and neck squamous cell carcinoma (HNSCC) compared to the general U.S. population, but little is known about HIV‐specific risk factors associated with the incidence and outcomes HNSCC. We aim to identify clinical and HIV‐specific risk factors associated with oropharyngeal and non‐oropharyngeal HNSCC incidence and outcomes separately. Methods We constructed a retrospective cohort study of 45,052 PLWH aged 18 or above from the national Veteran Affairs (VA) Corporate Data from 1999 to 2015. We extracted demographic data and risk factor information, including history of alcohol abuse, smoking, CD4 count (cells/μl), and percent of follow‐up time with undetectable HIV viral load as time‐updated variables. We calculated the age‐standardized incidence rates of oropharyngeal and non‐oropharyngeal HNSCC and estimated adjusted hazard ratios (HR). We also examined overall survival using Kaplan–Meier curves and adjusted HR. Results The standardized incidence rate of oropharyngeal and non‐oropharyngeal HNSCC in this veteran cohort of PLWH is 23.0 (95% confidence intervals (CIs): 17.1‐28.9) and 55.4 (95% CI: 46.5‐64.3) per 100,000 person‐years, respectively. Nadir CD4 count ≤200 was associated with an increased risk of non‐oropharyngeal HNSCC (HR: 1.78; 95% CI: 1.31‐2.30 vs >200). Five‐year overall survival of OPSCC (37.0%) was significantly lower than non‐oropharyngeal HNSCC (49.1%). Conclusions PLWH who receive care in the VA had higher age‐adjusted HNSCC incidence rates than reported in the general population, suggesting that HIV and immunosuppression play a role. Additional studies should be conducted to study the interaction between HPV and HIV., The elevated risk of both oropharynx cancer and non‐oropharyngeal head and neck cancer and poor survival among people living with HIV in the VA healthcare system suggests the host immune system interacts with smoking and HPV.

Background Disparities in access to screening often confound observed differences in human papillomavirus (HPV)-associated female genital tract cancer (FGTC) incidence between women living with human immunodeficiency virus (HIV; WLWH) and their HIV-negative counterparts. We aimed to determine if there have been changes in cancer risk among WLWH during the antiretroviral era in a single-payer health system. Methods We retrospectively selected WLWH and HIV-negative controls receiving care between 1999 and 2016 at the US Department of Veterans Affairs (VA) and identified FGTC diagnoses via Cancer Registry and International Classification of Diseases-9/10 codes. We extracted demographic and clinical variables from the VA’s Corporate Data Warehouse; evaluated incidence rates (IRs), incidence rate ratios, hazard ratios, and 95% confidence intervals (CIs) for cancer risk; and conducted survival analyses. Results We identified 1454 WLWH and compared them with 5816 matched HIV-negative controls. More WLWH developed HPV-associated FGTCs (total n = 28 [2.0%]; cervical = 22, vulvovaginal = 4, and anal/rectal = 2) than HIV-negative women (total n = 32 [0.6%]; cervical = 24, vulvovaginal = 5, and anal/rectal = 5) (log rank P < .0001). Cervical cancer IR was >6-fold higher for WLWH (204.2 per 100 000 person-years [py] [95% CI, 83.8–324.7]) than HIV-negative women (IR = 31.2 per 100 000 py [95% CI, 17.9–44.5]). The IRs for vulvovaginal and anal cancers were also higher in WLWH. Overall, WLWH were more likely to develop HPV-associated FGTCs compared with their HIV-negative counterparts (all log rank P values < .0001). Conclusions Veteran WLWH are more likely to develop HPV-associated FGTCs despite equal access to health care. Even in single-payer health systems, WLWH continue to require special attention to ensure guideline-based high-risk HPV screening for prevention of FGTCs.

Background Women living with HIV (WLHIV) have a high risk of developing invasive anal cancer. Anal cancer may be prevented with early detection and treatment of anal histologic high-grade squamous intraepithelial lesions (HSIL). However, there are limited data on the efficacy of anal HSIL treatment in WLHIV. Study design We conducted a retrospective study of WLHIV treated for anal HSIL under high-resolution anoscopy (HRA) guidance from January 1, 2007 to December 31, 2017 with at least one post-treatment visit at an urban tertiary care hospital. Results Forty-five WLHIV women with at least 1 follow-up evaluation after treatment for anal HSIL were identified. The median age was 46 years (range 35-66 years), 63% were African American, 27% were Hispanic/Latino, and 53% were current smokers. The mean absolute CD4 T-cell count was 516 cells/mm; 50% and 24% of the cohort had a history of cervical or vulvar HSIL respectively. The cumulative probability of anal HSIL recurrence was 29% at 12 months, 52% at 24 months, and 79% at 36 months post-treatment. Conclusion Most WLHIV treated for anal HSIL recurred within 3 years, suggesting need for continued surveillance after treatment. Our data contribute to the information needed to develop effective anal cancer prevention guidelines in WLHIV.

Objectives There are no uniform screening recommendations for anal cancer. Medical practice guidelines are now available on the use of Digital Anal Rectal Examinations (DARE) for the detection of anal cancer; however, because screening can result in more harm than benefit, our objective was to assess the evidence for use of DARE as a public health screening tool. Materials and methods We conducted a current critical appraisal of anal cancer literature using World Health Organization criteria for assessing the potential utility of a public health screening program. Results Digital Anal Rectal Examination satisfies most, but not all, World Health Organization criteria for a public health program that seeks to detect early invasive anal cancer in populations at high risk for anal cancer, most notably HIV-positive men who have sex with men; however, DARE is not appropriate when facilities for treatment are nonexistent. In addition, there are insufficient data on DARE sensitivity and specificity. Conclusions The mildly invasive nature of DARE, limited likelihood of adverse procedure-related events, cost-effectiveness and patient acceptability, as well as wide availability of DARE support consideration of its integration into screening for populations at high risk of anal cancer, especially HIV-positive men who have sex with men.

Recently, John Doe, an undocumented immigrant who was detained by United States Immigration and Customs Enforcement (ICE), was admitted to a hospital off-site from a detention facility. Custodial officers accompanied Mr. Doe into the exam room and refused to leave as physicians examined him. In this analysis, we examine the ethical dilemmas this case brings to light concerning the treatment of patients in immigration detention and their rights to privacy. We analyze what US law and immigration detention standards allow regarding immigration enforcement or custodial officers’ presence in medical exams and documentation of detainee health information. We describe the ethical implications of the presence of officers in medical exam rooms, including its effects on the quality of the patient-provider relationship, patient privacy and confidentiality, and provider's ability to provide ethical care. We conclude that the presence of immigration enforcement or custodial officers during medical examination of detainees is a breach of the right to privacy of detainees who are not an obvious threat to the public. We urge ICE and the US Department of Homeland Security to clarify standards for and tighten enforcement around when officers are legally allowed to be stationed in medical exam rooms and document detainees’ information.

People living with HIV have high rates of obesity and obesity-related comorbidities. Our study sought to evaluate weight trajectory in a retrospective cohort of people living with HIV and matched HIV-negative veterans (controls) and to evaluate risk factors for weight gain.This was a retrospective database analysis of data extracted from the VA Corporate Data Warehouse that included people living with HIV (n = 22 421) and age-matched HIV-negative controls (n = 63 072). The main outcomes were baseline body weight and weight change from baseline at 1, 2, and 5 years after diagnosis (baseline visit for controls).Body weight at baseline was lower in people living with HIV than in controls. People living with HIV on antiretroviral therapy (ART) gained more weight than did controls. In a sub-analysis of ART-exposed people living with HIV, age 50 years, African American race, body mass index (BMI) 25, CD4 ≤200, and HIV diagnosis year after 2000 were associated with more weight gain at year 1. Nucleoside reverse transcriptase inhibitors (NRTI) plus non-NRTIs (NNRTIs) were associated with less weight gain than NRTIs plus protease inhibitors, NRTIs plus integrase inhibitors, or NRTIs plus other agents at year 1.Among US veterans, those living with HIV had lower rates of obesity than age-matched HIV-negative controls; however, primarily in the first 2 years after starting ART, people living with HIV gained more weight than did controls.

To describe risk factors for mortality in HIV-associated Kaposi's sarcoma in an urban population in Dallas, Texas.Retrospective electronic medical record review of patients with HIV-associated Kaposi's sarcoma.Electronic medical records were reviewed from 1 January 2009 to 31 December 2018 for patients with a diagnosis of HIV and Kaposi's sarcoma by ICD-9 or ICD-10 codes. Demographics, HIV history, Kaposi's sarcoma history, treatment, and mortality data were collected. Mortality data was supplemented by an inquiry from the National Death Index (NDI). Survival analyses were performed using Cox proportional hazards analysis to determine independent predictors of mortality.Black patients had higher mortality than white or Hispanic patients (hazard ratio 2.07, 95% confidence interval 1.12-3.82), even after adjusting for covariates. This mortality difference correlates with higher rates of advanced Kaposi's sarcoma disease and KS-IRIS in black patients compared with other groups and is not explained by differences in CD4+ cell count, HIV viral load, engagement in care, or ART adherence at the time of cancer diagnosis.Despite nationwide trends showing decreased incidence and decreased mortality in Kaposi's sarcoma in the ART era, a high number of Kaposi's sarcoma cases and disparities in Kaposi's sarcoma outcomes persist in certain populations in the United States.

The US Centers for Disease Control and Prevention, the US Preventive Services Task Force, and the National Comprehensive Cancer Network recommend offering HIV testing for patients presenting for cancer care. Not recognizing and treating HIV infection adversely affects both cancer treatment and HIV outcomes. Acceptance rates of oncology patients for HIV screening are not known. Our tertiary cancer center inserted language requesting permission to screen for HIV infection into the consent forms for initial presentation for cancer care. Willingness to undergo testing was examined in 29 549 consecutive new patients. These were analyzed by gender and age. Overall, 80.9% of patients agreed to HIV screening. Incorporation of language requesting permission for HIV screening into the consent form provided at presentation for cancer care relieves clinicians from adding this task.

Each year, more than 8000 allogeneic stem cell transplantations (allo-SCT) are performed in the United States, with approximately 30% of these patients age ≥60 years. Allo-SCT recipients are at increased risk for developing human papillomavirus (HPV)-related precancer or second malignancy. It is important to evaluate HPV-related precancer or second malignancy among allo-SCT recipients to develop or enhance screening and preventive practice guidelines to improve patients’ survival and quality of life. In this retrospective matched case-control study, we estimated the cumulative incidence of HPV-related precancer or second malignancy in both male and female Medicare beneficiaries who underwent allo-SCT and compared it with the cumulative incidence in non-SCT controls and noncancer controls. Hematologic cancer patients age ≥18 years who underwent allo-SCT between 2002 and 2011 were matched 1:5 to non-SCT controls and to noncancer controls by age, sex, race/ethnicity, and duration of follow-up. Proportions of HPV-related precancer or second malignancy were estimated and compared between cases and controls using the chi-square test and logistic regression. Kaplan-Meier cumulative incidences were estimated and compared using log-rank tests. We identified 700 allo-SCT cases (median age, 64 years; median follow-up post-transplantation, 4.3 years) matched with 3159 non-SCT controls and 3302 noncancer controls. Approximately 3.7% of allo-SCT cases developed HPV-related precancer or second malignancy post-transplantation, compared with 1.9% of the non-SCT controls and 1.1% of the noncancer controls. The odds ratio of developing HPV-related precancer or second malignancy of allo-SCT cases compared with non-SCT controls and noncancer controls was 2.0 (95% confidence interval [CI], 1.25 to 3.18) and 3.5 (95% CI, 2.1 to 5.8), respectively. Both allo-SCT cases and non-SCT controls had significantly higher proportions and odds of developing HPV-related precancer or second malignancy compared with noncancer controls. The 5-year cumulative incidence in allo-SCT cases was 5%, compared with 2.1% in non-SCT controls and 1.2% in noncancer controls. The cumulative incidence of HPV-related precancer or second malignancy was statistically significantly higher in the allo-SCT than in either of the 2 matched control groups, and the non-SCT controls had a higher cumulative incidence of HPV-related precancer or second malignancy than the noncancer controls. The allo-SCT cases were at increased risk of developing HPV-related precancer or second malignancy compared with the non-SCT controls and noncancer controls. Routine screening of HPV-related precancer or second malignancy in allo-SCT recipients is needed to help prevent HPV-related precancer or second malignancy. © 2021 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.

Cervical cancer, a malignancy caused by persistent human papillomavirus (HPV) infection, develops in more than 500,000 women annually. More than 90% of deaths from cervical cancer occur in low- and middle-income countries. A common epidemiological feature of countries with high cervical cancer incidence is a high burden of intestinal helminth infection. The ability of intestinal helminths to trigger immunoregulation, resulting in a “tolerogenic” systemic immune environment, provides fertile soil for the persistence of oncogenic viruses such as HPV. Animal models have shown that intestinal helminth infection permits the persistence of some viruses, however, HPV-specific and human studies are lacking. Large, well-organized trials evaluating the consequences of intestinal helminth infection on the human immune system and HPV persistence may lead to improved strategies for HPV prevention in helminth-endemic regions of the world. Additionally, such studies would offer insight into the specific ways that intestinal helminth infection contributes to immunomodulation, which could identify new therapeutic targets for a range of diseases, from inflammatory disorders to cancer. In this review, we discuss the evidence for helminth-induced systemic and local immune dysregulation, discuss possible mechanisms by which chronic intestinal helminth infection may facilitate HPV persistence, and suggest novel helminth-related interventions that could offer a high leverage (if somewhat unconventional) approach to HPV and cervical cancer control in resource-constrained regions.

Objectives Oropharyngeal squamous cell carcinoma (OPSCC) incidence is rapidly increasing in the United States and around the world, driven in large part by infection with the human papillomavirus (HPV). HPV associated OPSCC (HPV+OPSCC) has been shown to have improved response to treatment relative to tobacco-associated OPSCC. However, improvement in patient survival has not been uniform. Subsets of OPSCC patients in the US and around the world continue to have poor oncologic outcomes. Although the drivers of this phenomenon remain unclear, there is increasing evidence that tobacco exposure plays an important role in modulating HPV+OPSCC clinical outcomes. Methods We conducted a review of the literature. Results We discuss the potential biological and epidemiological interplay between tobacco and HPV exposure in the context of OPSCC. Multiple retrospective and prospective cohorts show that HPV+OPSCC patients with a history of tobacco exposure have response to treatment and clinical outcomes distinct from HPV+OPSCC non-smokers which poses clinical and scientific challenges to be addressed over the next decade. Conclusions The interaction between tobacco exposure and HPV infection in the context of OPSCC has significant implications for both standard of care treatment regimens and development of novel therapeutic approaches, in particular those which incorporate immunomodulatory agents. Level of evidence 5.

To evaluate the risks of esophageal and stomach carcinomas in people living with HIV (PLWH) compared with the general population and risk factors for these cancers in PLWH.Retrospective cohort study in the Veterans Health Administration.We compared incidence rates for esophageal and stomach cancers in 44,075 HIV-infected male veterans with those in a matched HIV-uninfected cohort (N = 157,705; 4:1 matched on age and HIV-index date). We used Cox regression models to estimate Hazard ratios (HRs) and 95% confidence intervals (CIs) for associations with HIV infection and for cancer risk factors in PLWH.In unadjusted models, HIV infection was associated with increased risks of esophageal squamous cell carcinoma (ESCC; HR, 2.21; 95% CI: 1.47 to 3.13) and gastric cardia cancer (HR, 1.69; 95% CI: 1.00 to 2.85) but associated with lower risk of esophageal adenocarcinoma (EAC; HR, 0.48; 95% CI: 0.31 to 0.74). After adjusting for age, race/ethnicity, smoking and alcohol use, HIV infection remained statistically significantly associated with elevated risk for ESCC [adjusted hazard ratio (aHR), 1.58; 95% CI: 1.02 to 2.47], especially among HIV-infected patients with CD4 count ≤200 (aHR, 2.20; 95% CI: 1.35 to 3.60). HIV infection was not associated with risks of EAC (aHR, 0.82; 95% CI: 0.53 to 1.26), gastric cardia (aHR, 0.80; 95% CI: 0.33 to 1.94), or noncardia (aHR, 1.06; 95% CI: 0.61 to 1.84) cancers. Risk factors for these cancers in HIV-infected patients were otherwise similar to those in general population (eg, Helicobacter pylori for gastric noncardia cancer).HIV-infected individuals with low CD4 count are at highest risk for ESCC, but HIV infection was not independently associated with EAC or gastric cancer after adjusting for confounders.

The aims of this study were to: 1) determine prevalence of anogenital and oral HPV, 2) determine concordance between HPV at anal, perianal, scrotal/penile, and oral sites; and 3) describe factors associated with anogenital HPV types targeted by the 9-valent vaccine. Data were collected from 2012 to 2015 among men who have sex with men 18–26 years of age enrolled in a vaccine trial (N = 145). Penile/scrotal, perianal, anal, and oral samples were tested for 61 HPV types. Logistic regression was used to identify factors associated with types in the 9-valent vaccine. Participants’ mean age was 23.0 years, 55.2% were African-American, and 26.2% were Hispanic; 93% had anal, 40% penile, and 6% oral HPV. Among those with anogenital infection, 18% had HPV16. Concordance was low between anogenital and oral sites. Factors independently associated with a 9-valent vaccine-type HPV were: race (African-American vs. White, OR=2.67, 95% CI=1.11–6.42), current smoking (yes vs. no, OR=2.37, 95% CI=1.03–5.48), and number of recent receptive anal sex partners (2+ vs. 0, OR=3.47, 95% CI=1.16–10.4). Most MSM were not infected with HPV16 or HPV18, suggesting that they may still benefit from HPV vaccination, but anogenital HPV was very common, highlighting the importance of vaccinating men before sexual initiation. Clinical trial number: NCT01209325 Keywords: Adolescents, Clinical trials, Men who have sex with men, Vaccine, Human papillomavirus, HIV

Objective To estimate the prevalence of high-grade anal dysplasia in women with high-grade dysplasia or carcinoma of the cervix, vagina or vulva. Methods In this cross-sectional study, participants underwent anal cytology, anal HPV testing with Cervista HPV16/18 and high-resolution anoscopy (HRA). Patients with HSIL (high-grade squamous cell intraepithelial lesion) or greater on anal cytology or anal biopsy were referred to a colorectal surgery specialist for further evaluation. Results Seventy-five women were enrolled in the study, including 47 with cervical (cervix group), 10 with vaginal (vagina group), 15 with vulvar (vulva group), 1 with cervical and vaginal, and 2 with vulvar and vaginal disease. The median age in the cervix group (40 years (range 26–69)) was substantially younger than in the vagina (60 years (38–69)) and the vulva (59 years (36–75)) groups. Anal HSIL based on composite endpoints of the most severe cytology or histology result was diagnosed in 6 patients (8.0%). Anal cytology revealed HSIL in 2 (2.7%), atypical squamous cells of undetermined significance (ASCUS) in 12 (16.0%), low-grade squamous cell intraepithelial lesion (LSIL) in 2 (2.7%), and was normal in 59 (78.7%) patients. Anal HPV16/18 test was positive in 15 (20.0%), negative in 48 (64.0%) and insufficient in 12 (16.0%) patients. Of the 6 women with high-grade anal dysplasia, three (50%) had a positive anal HPV16/18 test. No case of anal cancer was observed. Conclusion Our results suggest that the prevalence of anal HSIL is elevated among women with HPV-related lower genital tract dysplasia or cancer. To further support the inclusion of this high-risk group into screening guidelines for anal dysplasia, further studies are necessary to determine what screening strategy is suited to this population.

IntroductionSquamous cell carcinoma of the anus is a common cancer among sexual minority men, especially HIV-positive sexual minority men; however, there is no evidenced-based national screening protocol for detection of anal precancers. Our objective is to determine compliance with annual anal canal self-sampling or clinician-sampling for human papillomavirus (HPV) DNA.Methods and analysisThis is a prospective, randomised, two-arm clinical study to evaluate compliance with annual home-based versus clinic-based HPV DNA screening of anal canal exfoliated cells. The setting is primary care community-based clinics. Recruitment is ongoing for 400 HIV-positive and HIV-negative sexual minority men and transgender persons, aged >25 years, English or Spanish speaking, no current use of anticoagulants other than nonsteroidal anti-inflammatory drugs and no prior diagnosis of anal cancer. Participants are randomised to either receive a swab in the mail for home-based collection of an anal canal specimen at 0 and 12 months (arm 1) or attend a clinic for clinician collection of an anal canal specimen at 0 and 12 months (arm 2). Persons will receive clinic-based Digital Anal Rectal Examinations and high-resolution anoscopy-directed biopsy to assess precancerous lesions, stratified by study arm. Anal exfoliated cells collected in the study are assessed for high-risk HPV persistence and host/viral methylation. The primary analysis will use the intention-to-treat principle to compare the proportion of those who comply with 0-month and 12-month sampling in the home-based and clinic-based arms. The a priori hypothesis is that a majority of persons will comply with annual screening with increased compliance among persons in the home-based arm versus clinic-based arm.Ethics and disseminationThe study has been approved by the Medical College of Wisconsin Human Protections Committee. Results will be disseminated to communities where recruitment occurred and through peer-reviewed literature and conferences.Trial registration numberNCT03489707.

This chapter discusses the role of virally mediated and non-virally mediated AIDS-associated and non–AIDS-associated malignancies. The learner will review the epidemiology and role of antiretroviral therapy on the impact of AIDS-defining malignancies. The chapter covers the role of human herpes virus-8 in the development of Kaposi’s sarcoma, the role of Epstein–Barr virus in primary central nervous system lymphoma, and other HIV-associated lymphomas. It reviews and the role of human papillomavirus vaccination in virally mediated anogenital squamous cell cancer. Non-AIDS-defining malignancies, including lung, prostate, oropharyngeal, liver, breast, and pancreatic cancers, are covered. Lastly, the text emphasizes that antiretroviral initiation is of utmost importance for all AIDS-defining malignancies and non-AIDS-defining malignancies and summarizes the National Cancer Center Network Guidelines for HIV malignancies.

PURPOSE/OBJECTIVE(S) Low and middle-income countries (LMICs) are significantly under-represented in cancer research due to a lack of research capacity rooted in historical inequalities. Training in-country physicians in clinical research is one of the most sustainable ways to address the shortage of research in LMICs. As part of an academic partnership between MD Anderson Cancer Center in Houston, TX (MDA) and Cancer Diseases Hospital in Lusaka, Zambia (CDH), an international virtual clinical research course for clinical oncology fellows at CDH was piloted in Fall 2020 to address a significant need for a structured clinical research curriculum. MATERIALS/METHODS The virtual clinical research course took place from August to November 2020 and involved 14 weekly hour-long lectures (13 by MDA faculty, one by CDH faculty) on topics including identifying a research question, study design, clinical trials, research ethics, biostatistics, and scientific writing. The course was attended by 15 clinical oncology fellows. Eight senior fellows were paired with a longitudinal MDA and CDH faculty member and MDA resident/fellow mentor in their area of interest to support a research protocol. Anonymized pre- and post-course surveys were administered with 5-point Likert scale academic self-efficacy inventories and open-ended qualitative questions. Descriptive statistics were used to summarize the findings. RESULTS A total of 12/15 participants (80%) completed the pre-course survey and 11/15 (73%) completed the post-course survey. Average scores pre- and post-course, respectively, for research interest and motivation (5.0, 4.9), comfort reading and evaluating medical literature (3.7, 4.5), developing a study question and design (2.8, 4.0), collecting and managing data (3.3, 4.0), independently performing and publishing research (2.3, 3.7), and satisfaction with mentorship and profession (3.0, 4.2) demonstrated an increase across multiple domains. As of December 2020, there were eight active research proposals led by CDH clinical oncology fellows and there had been 21 meetings and 27 hours of MDA-CDH mentorship time. Positive themes from open-ended feedback included clear lectures, meaningful relationships with mentors, and utility of presenting research proposals for feedback while constructive themes included desire for more teaching on statistical analysis and incorporation of self-assessment modules. CONCLUSION Clinical research is essential to develop effective, evidence-based interventions to the unique cancer care challenges that occur in LMICs. The results from the pilot virtual MDA-CDH research course, which led to improvements in academic self-efficacy scores, support for research proposals led by CDH clinical oncology fellows, and formation of longitudinal mentorship groups demonstrate the feasibility of conducting a virtual longitudinal research workshop model. Continued collaboration and future follow-up will be needed to demonstrate effectiveness and impact.

A history of gout, arthritis due to hyperuricemia, has been associated with decreased risk for neurodegenerative diseases such as Parkinson's disease. We performed a population-based case-control study in the US Department of Veterans Affairs (VA) medical centers nationwide to assess if gout or hyperuricemia is similarly associated with the ocular neurodegenerative condition glaucoma.We used ICD-9 codes to identify a nationwide cohort of patients examined at VA healthcare eye clinics between 2000 and 2015 with a diagnosis of open-angle glaucoma (OAG) or of glaucoma suspect. We used incidence density matching to choose controls. We used multivariable logistic regression to examine associations between a history of gout and uric acid (UA) levels on relative risk of OAG or glaucoma suspect.There were 1,144,428 OAG or glaucoma suspect cases and 1,144,428 matched controls. Veterans with a history of gout had a small significant decreased risk of OAG compared to controls (ORProspective research in other cohorts is needed to confirm our findings in veterans suggesting a history of gout is associated with a small decreased relative risk of glaucoma.