OBJECTIVES:Assess the distribution of oral HPV genotypes and examine their associations with age and HIV-related factors among men living with HIV. METHODS:This cross-sectional study analyzed baseline data from a randomized, double-blinded, placebo-controlled Phase III trial ('ULACNet-201'; NCT04255849) assessing the 9vHPV vaccine's efficacy in PLWH. Participants included men aged 20-50 years from Brazil, Mexico, and Puerto Rico, on antiretroviral therapy for ≥6 months. Oral HPV genotypes were assessed using the SPF10 PCR-DEIA-LIPA25 on oral gargles. Demographics and HIV-related characteristics were collected via questionnaires, and clinical assessments were conducted. ANOVA and chi-square tests assessed associations with age groups and HPV infection. RESULTS:Among 700 participants, oral HPV was detected in 27.9%, with HR-HPV detection at 11.0%. 4vHPV and 9vHPV types were detected in 4.9% and 8.9% participants, respectively. The most detected HR-HPV types were HPV 16 (2.4%), HPV 33 (2.0%), and HPV 52 (2.0%). No significant age-specific differences in oral HPV detected were observed. Higher detection rates of any HPV and HR-HPV were observed among participants with baseline CD4 counts below 200 cells/mm³ or a history of AIDS-defining conditions. CONCLUSIONS:Oral HPV genotyping in men with HIV reveals distinct oncogenic patterns, underscoring the need to monitor long-term OPSCC risk.

Minor histocompatibility antigen (mHAg)-specific alloreactive donor T cells cause graft vs. host disease (GVHD) in matched related donor allogeneic hematopoietic cell transplantation (HCT). In a phase I trial, we expanded and infused (on day -2) mHAg-specific donor regulatory T cells (Treg) together with sirolimus-based pharmacologic prophylaxis to examine safety and preliminary efficacy of this GVHD prevention approach. We employed a 3+3 phase I design escalating Treg dose in 4 levels: 0.5 x 105/kg, 1 x 105/kg, 2 x 105/kg, and 4 x 105/kg. Dose-limiting toxicity (DLT) included grade 4-5 related infusion reaction, grade 4-5 unexpected organ toxicity, grade III-IV acute GVHD, or treatment-related death. Secondary and exploratory measures examined acute and chronic GVHD, survival outcomes, and Treg clone (TCR-Seq) expansion in culture, and in-vivo longevity and expansion post-HCT. 15 subjects were included (N=3 each per dose levels 1-3, and N=6 in dose level 4). No DLT were observed, and 4 x 105/kg Treg was identified as MTD. Median follow up for survivors was 41.7 months (range 14.5-72.8). The day 100 cumulative incidence of grade II-IV acute GVHD was 13% (95% CI 2-35%). NIH moderate/severe chronic GVHD by 1 year was 6.7% (95% CI 0.36-27%) and by 3 years was 20% (95%CI 4.4-44%). Overall survival was 73% (95% CI 54-100%). Treg clones expanded in culture, and demonstrated post-HCT lineage fidelity, persistence, and in-vivo expansion. This translational trial supports mHAg-specific expanded donor Treg as a novel GVHD prevention strategy, and demonstrates expanded donor Treg clones can persist and expand through one-year post-HCT. NCT01795573.

Prolonged or indefinite systemic therapy remains standard for advanced clear cell renal cell carcinoma (ccRCC), often resulting in cumulative toxicities and treatment burden. We conducted a single-arm phase 2 trial (ClinicalTrials.gov identifier: NCT02964078) of a fixed-duration regimen of anti-PD1 pembrolizumab plus high-dose interleukin-2 in treatment-naive advanced ccRCC. Primary objectives of safety and response were previously reported. The study met its primary endpoint with an overall response rate exceeding the pre-specified threshold of 45%. Here we report long-term follow-up (median follow-up of 76.4 months) including overall response, progression-free survival, treatment-free interval, and correlative analysis. Among 26 patients treated, the objective response rate was 73%, with complete responses in 42% of patients. Median overall survival was >84 months with a 5-year restricted mean survival time of 48.6 months. Median progression-free survival was 19.3 months, and median treatment-free interval was 23.8 months. 42% of patients remained treatment-free at the 5-year timepoint. No grade 5 adverse events occurred, and no patients with durable disease control experienced persistent grade ≥2 toxicities. Correlative analyses identified exploratory immune patterns associated with durable benefit, including enrichment of CD16⁺ natural killer cells, suppression of PD-1⁺ T-cell frequencies, and coordinated chemokine, complement, and PKC/TGF-β pathway activation.

PURPOSE:We report long-term survival and comprehensive molecular biomarker analyses of a phase II trial evaluating the combination of cetuximab and nivolumab in recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). PATIENTS AND METHODS:The long-term follow-up data were obtained from a phase II trial (NCT03370276). Archived tumors and serially collected plasma cell-free DNA were characterized by comprehensive genomic analyses. Immune markers were measured in tumor cores and margins by multiplex IHC. RESULTS:At a median follow-up of 47.4 months, the median overall survival (OS) and 2-year OS rate were 12.7 months and 32% in all evaluable patients (n = 88) and 17.5 months and 35% in patients who had no prior therapy for R/M HNSCC (n = 43). The survival efficacy was similar between patients with p16-negative and p16-positive tumors, but the response rate was significantly higher in patients with p16-negative tumors. The clonal tumor mutational burden, hypoxia score, and EGFR pathway score were significantly higher in p16-negative compared with p16-positive tumors. Loss of heterozygosity of MHC class I was significantly more frequent in nonresponders, and APOBEC-associated mutagenesis was elevated in responders. Gene expression profiling and multiplex IHC analyses revealed a more inflamed tumor microenvironment in responders regardless of p16 status. CONCLUSIONS:Our long-term follow-up study indicates that the combination of cetuximab and nivolumab is efficacious and tolerable and that patients with p16-negative R/M HNSCC may have greater benefit from this combination.

The restricted mean survival time (RMST) analysis has been used extensively in clinical research involving time-to-event endpoints. The threshold time up to which the restricted mean survival is calculated has a critical impact on the analysis results. However, identifying an optimal threshold time for treatment comparison, which corresponds to the greatest restricted mean lifetime difference between groups, remains unclear in practice, and no analytical method has been developed on this topic. We present a novel method for determining the threshold time in the RMST analysis to compare two groups. Simulation studies indicate that this method leads to high statistical power and controlled type I error rate compared with existing methods. The proposed method is illustrated in two applications: (1) a clinical oncology study for non-small-cell lung cancer treatments comparison given a programmed death-ligand 1 biomarker measurement, and (2) a gerontology study of instrumental activities for care recipients with dementia.

Data modeling in biomedical research often operates in the small-sample regime, where the number of observations is small relative to the data dimensionality; the detrimental effects of limited sample sizes are well documented in cancer studies. Synthetic data offers a potential solution to data shortfalls provided that the data generated is an adequate facsimile of the underlying distribution; the adequacy of such synthetic data remains an open-ended problem. In this work, we evaluate a synthetic generator proposed previously. The generator applies a series of transformations to the observed data to accommodate the small-sample size resulting in an uncoupled representation, where uncorrelated marginal distributions are modeled with optimized univariate kernel density estimation. In this report, (1) we develop a nonparametric method for assessing multivariate similarity based on the Cramér-Wold theorem and random projection testing, (2) investigate when the absence of bivariate correlation approximates independence in a non-normal setting, and (3) evaluate artifacts induced by data compression. The presentation is primarily methodological; low-dimensional data were used so each stage of the generation process could be analyzed explicitly. A formal testing framework was developed by comparing random projection level outcomes with a two-sample test, modeling these outcomes as Bernoulli trials, aggregating replicate outcomes within each projection direction, and pooling outcomes across many directions, yielding a scalable standardized normal test-statistic. The key innovation was decoupling the two-sample test significance level from that governing finalized normal inference. We showed the same projection framework also evaluates the full multivariate covariance structure. The generator produced high-fidelity multivariate synthetic data when the bivariate correlation approximates independence in the non-normal setting; in highly compressed data, residual modes were best modeled as normally distributed regardless of their intrinsic distributional form. Ongoing work includes applying these methods to higher-dimensional, diverse data.

Alcohol consumption is recognized as a risk factor for oropharyngeal cancer. However, its role in oral human papillomavirus (HPV) infection among people living with HIV (PLWH) remains unclear. This cross-sectional study analyzed baseline data from 699 men living with HIV (MLWH) enrolled in the multicenter ULACNet-201 trial (NCT04255849) to assess oral HPV infection by drinking behavior, examine the association between alcohol consumption and HPV infection, exploring smoking as a potential effect modifier. Oral gargle specimens were tested for high-risk (HR-HPV) and low-risk (LR-HPV) HPV genotypes using SPF10 PCR-DEIA-LiPA25. Logistic regression estimated adjusted odds ratios (ORs, 95% CIs) controlling for key covariates and explored heterogeneity by smoking status. Alcohol use in the past month was reported by 76.4% of participants, with 6% classified as heavy drinkers and 27% as binge drinkers. Oral HPV infection was similar between drinkers and nondrinkers (27.7% vs. 28.5%), with comparable rates for HR-HPV (11% vs. 10.9%) and LR-HPV (18.7% vs. 19.7%). Alcohol consumption was not associated with HR-HPV overall, and exploratory analysis found no evidence of effect modification by smoking status. A possible interaction between alcohol consumption and smoking status was observed for LR-HPV, but these findings should be interpreted cautiously. Further longitudinal studies are needed.

EGFR inhibitor (EGFRi) therapies have been FDA-approved for metastatic colorectal cancer (CRC). However, extended RAS/RAF testing required in the drug labels, identifies only non-responders, and only 50

Background:Human papillomavirus (HPV)-related oropharyngeal cancer arises from persistent high-risk HPV (HR-HPV) oral infection. Smoking is a risk factor for oral HPV, but alcohol's role is unclear. We investigated the association between alcohol consumption and oral HPV infection. Methods:This cross-sectional analysis used baseline data from the HIM Study. Oral HPV was detected with SPF10 PCR-DEIA-LiPA25 on oral gargle specimens. Associations between alcohol consumption and oral HPV were assessed using adjusted logistic regression models, exploring effect modification by smoking. Findings:Among 3121 males (median age 33 years, interquartile range [IQR] 25, 41), 39% were from Brazil (n = 1229), 32% from Mexico (n = 1014), and 28% from the United States (n = 878); 76% (n = 2365) reported alcohol use in the past month (median 8 drinks, IQR 0, 24). Oral HPV was detected in 20% (n = 469) participants reporting alcohol use, including 6.1% (n = 145) with HR-HPV and 14% (n = 324) low-risk HPV (LR-HPV). HR-HPV detection increased with alcohol intake, peaking at 7.6% (n = 75) among those consuming ≥16 drinks/month (p = 0.005). Consuming ≥16 drinks/month was independently associated with HR-HPV after adjustment (adjusted odd ratio [aOR] 1.60, 95% confidence interval [CI] 1.07, 2.40), whereas consuming 3-15 drinks was not (aOR 1.15, 95% CI: 0.76, 1.76). Exploratory stratified analyses showed aOR 2.57 (95% CI: 1.37, 4.96) in males who had never smoked and 1.12 (95% CI: 0.67, 1.88) in those who currently or formerly smoked, with no evidence of effect modification. Interpretation:Higher monthly alcohol consumption was modestly associated with oral HR-HPV in this cross-sectional analysis; longitudinal studies are needed to assess extension to oral HPV persistence, a recognized precursor of cancer. Funding:National Institute of Health, American Cancer Society.

9553 Background: Metastatic uveal melanoma (mUM) has a poor prognosis with modest response to immune checkpoint blockade (ICB). Inactivating mutations in BRCA-1 associated protein 1 ( BAP1 ) are common in mUM leading to deficient homologous recombinant DNA repair and increasing reliance on alternate repair pathways, including poly[ADP-ribose] polymerase (PARP). We investigated if the PARP inhibitor olaparib could improve objective response to pembrolizumab (PEM) in mUM (NCT05524935). Methods: Key eligibility included mUM with measurable disease, ECOG 0-1, and adequate organ function. Prior liver directed therapy was allowed. Patients (pts) received PEM 200mg IV every 21 days plus oral olaparib 300mg BID till progression, toxicity, or completion of 2 years of treatment. In a Simon 2-stage optimal design, > 1 response by RECIST 1.1 in 12 evaluable patients would permit accrual to expand to 37 pts. Results: Twelve eligible mUM pts, 6 male and 6 female, median age 59 years (42, 84) were treated in stage 1 of this trial. Most pts (11/12; 92%) had both liver and extra-hepatic metastatic disease; 5 pts had elevated serum LDH at baseline. Seven pts (58%) were naïve to prior systemic therapy; 4 had prior liver directed therapy. There was no objective response observed; best response was stable disease (SD, n=5), remainder (n=7) with progression; disease-control rate was 42%. One patient continues treatment at 13 months with ongoing SD. Of 4 pts who received prior tebentafusp, three had SD lasting greater than 6 months. At median follow-up of 13 months, the median progression-free survival (PFS) was 3.6 months (95% CI: 2.2, 8.3), and median overall survival (OS) was 13.8 months (95% CI: 2.5, 24.3). Six-month PFS and OS were 0.42 (95% CI: 0.15, 0.67) and 0.83 (95% CI: 0.48, 0.96) respectively; one year OS was 0.73 (95% CI: 0.37, 0.91). Most common (≥ 25%) all grade treatment related adverse events (AEs) were fatigue, arthralgia, diarrhea, nausea/vomiting, dyspnea, anemia, abdominal pain, bloating, anorexia, muscle weakness, pruritus, rash, vitiligo, dyspnea, cough, hypertension, muscle weakness, ↑ AST, ↑ alkaline phosphatase, ↓ lymphocyte count, ↑ glucose, ↑ potassium and ↓ albumin. Grade 3 AEs were infrequent; nausea, anorexia, dehydration, hypotension, and muscle weakness (all n=1); there was no treatment related death. 5/12 (42%) pts required a dose reduction for olaparib. Conclusions: The addition of olaparib to pembrolizumab was well tolerated but did not result in any objective response in molecularly unselected mUM. Landmark survival results appear clinically meaningful and likely related to disease control with stable metastatic burden. Ongoing biomarker studies of tumor tissue (BAP1, PD-L1, PARP1, TIL) and blood may help discern which patients could benefit from this combination regimen. Optimal sequencing of ICB with tebentafusp in HLA-A*02:01+ mUM should be explored further. Supported by Merck, Inc. Clinical trial information: NCT05524935 .

3099 Background: Prognosis in mUM is poor with limited efficacy of currently available therapies. The melanocortin-1 receptor (MC1R) is an attractive target for radiopharmaceutical therapy given high expression in UM. 225 Ac-MTI-201 is a novel alpha particle emitting MC1R bound radiopharmaceutical with high biostability, affinity, and MC1R-specific cytotoxicity with defined dosimetry and pharmacokinetics in pre-clinical studies. Methods: In this first-in-human study (NCT05496686) of a single IV dose of 225 Ac-MTI-201, we enrolled mUM patients (pts) who had disease progression on at least 1 prior therapy. Pts had adequate organ and functional status; prior radiotherapy to >25% of bone marrow was exclusionary. The primary objective was safety and toxicity of 225 Ac-MTI-201 with secondary endpoints of pharmacokinetics (PK) and clearance of 225 Ac-MTI-201, response rate, progression-free survival (PFS), and overall survival (OS). Up to 12 dose levels [from 4.7 microcurie (µCi) to 1327 µCi] for 225 Ac-MTI-201 were planned per a modified continual re-assessment method (CRM) with a cohort size of one based on dose limiting toxicity (DLT) assessment within 28 days of drug administration using CTCAE v5.0. Response was assessed by RECIST 1.1. Results: Sixteen pts (8 male, 8 female), median age 63 years (43, 84) have been treated. Median number of prior systemic regimens was 2 (0,4), 8 pts had prior liver directed treatment. Dose of 225 Ac-MTI-201 was escalated to level 6 (152 µCi) when one DLT (G4 thrombocytopenia and G4 neutropenia) was observed requiring de-escalation per CRM. A second DLT (G4 neutropenia) at level 5 (76 µCi) required expansions at levels 4 (38 µCi; n=5) and 5 (n=6) where all remaining pts were treated without further DLT with 1 pt currently pending final DLT assessment. Adverse events (AEs) were mostly G1-2 including leucopenia, lymphopenia, neutropenia, thrombocytopenia, anemia, nausea, fatigue and ↑ AST. Reversible myelosuppression [lymphopenia (7), neutropenia (5), thrombocytopenia (2)] was the most common > G3 AE. No non-hematological DLT was seen. Best response was stable disease (4/15; 27%); seen at dose levels 4 and 5. The median PFS was 2.30 months (95% CI: 1.84, 3.65); 6-month PFS was 0.07 (95% CI: 0.0, 0.26) and 12-month OS was 0.39 (95% CI: 0.13, 0.64). Median distribution phase half-life (n=15) was 6.19 minutes followed by a slower median elimination phase half-life of 74.06 minutes with significant positive correlation between fast and slow half-lives (Spearman = 0.696, p= 0.0039), independent of dose level. Conclusions: Single dose administration of 225 Ac-MTI-201 with dose escalation to 76 µCi appears safe and feasible in mUM. Disease stability in this difficult to treat population is encouraging and a multi-dose study of 225 Ac-MTI-201 in mUM is planned pending final pt DLT assessment. 225 Ac-MTI-201 has Orphan Drug designation for mUM. Clinical trial information: NCT05496686 .

136 Background: Androgen deprivation therapy (ADT), used for advanced prostate cancer (PC), has shown mixed associations with dementia in previous studies. We evaluated whether ADT for PC raises the risk of dementia in a large, real-world sample, hypothesizing that patients receiving ADT for PC would have higher odds of dementia compared with PC patients not treated with ADT. Methods: A de-identified open-claims real-world database (NorstellaLinq) included patients age ≥40 years, diagnosed with PC between August 1, 2015, through December 31, 2021, with follow-up data through March 31, 2023. We used target trial emulation, treating the date of PC diagnosis as day 0 and examining whether receiving ADT within 180 days was associated with risk of dementia at ≥365 days. Death was inferred for patients with no claims for ≥12 months. We used competing risk analyses, accounting for death as a competing risk. Covariates included age, presence of metastatic PC, other non-PC cancers, medical comorbidities, and race, derived using an algorithm based on Bayesian Improved Surname Geocoding. Results: Of the 1,495,181 patients who met the study criteria, 9.4% received ADT within 180 days after PC diagnosis; 16% died during the study. Dementia diagnoses after day 365 were observed among 4.2% of ADT recipients and 4.2% of patients not treated with ADT. Using ADT within 180 days after PC diagnosis was not associated with dementia (aHR [adjusted hazard ratio]=0.993, 95% CI 0.97–1.02, p=0.639); ADT was associated with higher adjusted risk of death (aHR=1.268, 95% CI 1.25–1.28, p=3.5e –285 ). Sensitivity analyses found similar results. Compared with White patients, Black (aHR=1.40, 95% CI 1.34–1.46, p=8.9e −54 ) and Hispanic patients (aHR=1.26, 95% CI=1.21–1.32, p=6.7e −23 ) had higher risk of dementia. In analyses examining dementia risk among patients receiving various classes of ADT, patients receiving gonadotropin-releasing hormone agonists had higher risk of dementia (aHR=1.05, 95% CI 1.02–1.090) compared to patients not receiving ADT, and patients who received androgen receptor inhibitors (aHR=0.91, 95% CI 0.86–0.95) or androgen synthesis inhibitors (aHR=0.85, 95% CI 0.77–0.95) had lower risk of dementia than patients not receiving ADT. Conclusions: Contrary to our hypotheses, we found no increased risk of dementia among PC patients treated with ADT compared with those not treated with ADT in this large, real-world sample. However, future studies should further examine the findings of higher dementia risk among Black and Hispanic patients and among patients receiving gonadotropin-releasing hormone agonists.

Background: Former and current smokers in lung cancer screening remain at elevated risk for lung cancer despite smoking cessation. We and others have shown that curcumin (CUR) exhibits anti-inflammatory and antiproliferative effects but is limited by poor bioavailability. However, since CUR is lipophilic, co-administration with ω-3 FAs represents a mechanistically rational strategy to enhance delivery and target complementary pathways, including signal transducer and activator of transcription 3 (STAT3) and the transcription factor NF-κB (NF-κB) signaling for lung cancer chemoprevention. Methods: We conducted a randomized, single-blind, placebo-controlled Phase II pilot study evaluating CUR combined with ω-3 FAs in high-risk former and current smokers with CT-detected pulmonary nodules. Participants received intervention agents with active-dose groups (low dose = 3; high dose = 9) or a placebo (n = 7) for 6 months. Primary endpoints included radiologic changes in nodule size, number, and density. Secondary endpoints included safety, adherence to the study agent and exploratory biomarker analyses. Correlation analyses of imaging-derived metrics were performed to assess relationships among LDCT parameters. Results: Nineteen participants were enrolled (intervention, n = 12; placebo, n = 7). Eighteen (11 intervention, 7 placebo) subjects completed post-intervention imaging. One subject was unable to complete follow-up and study-related procedures. Data from the treatment arms were pooled for analysis and comparison with the placebo arm. No statistically significant between-group differences were observed in primary imaging endpoints. The intervention was well tolerated, with predominantly grade 1 adverse events. Exploratory analyses demonstrated consistent positive correlations among established imaging biomarkers, with clustering of size-based metrics (mean diameter, volume, sum of longest diameters) and density-based parameters. Multidimensional scaling supported this structure, indicating internal coherence among imaging-derived endpoints. Conclusions: Although no statistically significant treatment effect on the image biomarkers was observed, this pilot study demonstrates feasibility challenges and identifies coherent imaging biomarkers that may serve as intermediate endpoints in early-phase chemoprevention trials. These results support further investigation of strategies utilizing agent combinations with enhanced bioavailability and safety and refinement of trial design in high-risk lung cancer patient populations.

Background The immunologic features of tumor-infiltrating lymphocyte (TIL) infusion products and their interactions with the tumor microenvironment that govern clinical responses in metastatic melanoma remain incompletely characterized. Methods We performed integrated immunophenotypic and spatial transcriptomic profiling of TIL infusion products and matched tumor microenvironments from patients treated on early-phase clinical trials. Results The durable objective response rate was 36%, with a median progression-free survival of 8 months among patients treated with TIL therapy with or without additional therapies. Responders exhibited infusion products enriched for CD8+ T cells, stem-like memory subsets, and LAG-3-expressing CD8+ T cells, together with enhanced peripheral TIL persistence. The abundance of infused LAG-3+ TILs correlated with tumor reactivity and prolonged progression-free survival. Prior immune checkpoint inhibitor exposure was associated with reduced CD8+ stem cell memory T cell frequency and diminished co-stimulatory receptor expression, suggesting impaired TIL fitness. Tumors enriched for tertiary lymphoid structures and spatial immune programs characterized by antigen presentation, interferon signaling, and B cell activation were independently associated with clinical benefit. Conclusions These findings define an integrated framework linking TIL composition and the tumor microenvironment to therapeutic response and identify potential biomarkers and biological features that may guide patient selection and optimization of TIL therapy. Funding This work was funded by Iovance Biotherapeutics, the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation, the Melanoma Research Alliance, the Donald A. Adam Melanoma & Skin Cancer Center of Excellence, American Cancer Society-Leo and Anne Albert Charitable Foundation Research Scholar Grant, and Melanoma SPORE (P50CA168536).

Background: Androgen deprivation therapy (ADT) is widely used in the management of prostate cancer (PCa) and remains a cornerstone of treatment across multiple disease settings. Although ADT contributes substantially to disease control, it also induces significant adverse metabolic and body composition changes. These alterations include loss of lean mass, increased fat mass, and deterioration in muscle quality, together contributing to a clinical phenotype consistent with sarcopenic obesity (SO). Importantly, ADT-induced SO is characterized not only by reductions in skeletal muscle mass but also by impaired muscle quality, particularly the fatty infiltration of skeletal muscle, or myosteatosis, an underrecognized but defining feature of this syndrome. Methods: This narrative review examines current evidence regarding interventions aimed at mitigating sarcopenic obesity in men treated with ADT for prostate cancer, identifies key gaps in the literature, and proposes a mechanism-driven path forward for intervention development. Results: Several exercise- and nutrition-based interventions have been evaluated in men receiving ADT and demonstrate improvements in selected outcomes such as muscle strength, body composition, and metabolic parameters. However, most studies have been limited by small sample sizes, short intervention durations, and a focus on isolated intervention components. Importantly, muscle quality and intramuscular fat infiltration (myosteatosis), a central component of sarcopenic obesity, have rarely been incorporated as biomarkers or endpoints in intervention trials targeting men receiving ADT. Conclusions: Future interventions designed to mitigate SO and its associated metabolic abnormalities should evaluate comprehensive, bundled strategies initiated early during ADT and sustained long enough to capture clinically meaningful changes. Outcomes should include biomarkers of muscle mass, strength, and quality, including imaging-based measures of myosteatosis, along with metabolic syndrome markers, inflammatory mediators, functional outcomes, adherence, and quality of life. These changes should evaluate the correlation with underlying biological mechanisms such as NF-κB signaling and pro-inflammatory cytokines. Such data may inform future phase III trials and ultimately support clinical strategies to mitigate ADT-related sarcopenic obesity and its downstream cardiometabolic and oncologic consequences.

Supplementary Table S3: Association of physical activity and hazard of cancer-specific death among 895 cancer patients treated with immune checkpoint inhibitors.

HPV-related oropharyngeal squamous cell carcinoma (OPSCC) has increased significantly among men, especially among men living with HIV. HPV vaccines have proven efficacy in preventing persistent anogenital HPV infections. However, less is known regarding vaccine efficacy against persistent oral HPV infection, the obligate precursor of OPSCC. In 2020, the 9-valent HPV (9vHPV) vaccine received accelerated approval from the FDA for the indication of prevention of HPV-related OPSCC and other head and neck cancers, pending confirmation of clinical benefit in further trials. Currently a Phase III trial is ongoing to evaluate efficacy of the 9vHPV vaccine in preventing persistent oral HPV infection in immunocompetent men (NCT04199689); however, no trials have been conducted in people living with HIV. Here we describe the rationale, design, and study population characteristics of the first randomized (1:1), double-blind, placebo-controlled trial evaluating the efficacy and immunogenicity of the 9vHPV vaccine in preventing persistent oral HPV infection in men aged 20-50 living with HIV. The primary objective is to demonstrate that the 9vHPV vaccine when given in a 3-dose regimen (Day 1, Months 2 and 6) reduces the incidence of persistent (≥6 months) oral HPV infection with 9vHPV vaccine types 6, 11, 16, 18, 31, 33, 45, 52, and 58 in men living with HIV who are oral HPV negative to the relevant HPV type at enrollment, compared with placebo. The trial began in February 2021 and completed enrollment of 700 men at clinical sites in Brazil, Mexico, and Puerto Rico in February 2024. The secondary objectives are to evaluate the vaccine-induced serum anti-HPV 6, 11, 16, 18, 31, 33, 45, 52, and 58 responses, and the safety and tolerability of the 9vHPV vaccine in men living with HIV. Results from this study may inform policy regarding vaccination strategies for people living with HIV. ClinicalTrials.gov Identifier: NCT04255849.

Supplementary Table S1: Univariable and multivariable associations of physical activity and hazard of death among 930 cancer patients treated with immune checkpoint inhibitors.

Supplementary Figure S1: Temporal sequence of analyzed variables.

In response to the growing burden of HPV-associated oropharyngeal cancer, this study investigated clearance of oral HPV, the obligate precursor, in a longitudinal cohort of men from the US, Brazil, and Mexico. Oral gargles collected every 6 months from the HPV Infection in Men Study were HPV genotyped using SPF10 PCR-DEIA-LiPA25. Oral HPV infection clearance and associated factors were assessed using Kaplan-Meier curves and Cox proportional hazards models, respectively. Median follow-up was 44.8 months with 403 and 186 men with an incident and prevalent oral HPV infection, respectively; and lower probability of clearance observed in prevalent infections. Infections were less likely to clear in the presence of increased sexual behaviors; and among prevalent infections, older men were less likely to clear their infection. Here, we report differences in prevalently and incidently detected infections with sexual behavior as a key factor and older age as a potential factor associated with clearance.