Advances in antiretroviral therapy (ART) have normalized the life expectancy of people living with HIV (PLWH) but have been linked to a premature presentation of age-related comorbidities, including cancer. Telomere length (TL) is a marker of cellular aging and was investigated in blood leukocytes from 78 PLWH on ART, compared with 163 HIV-uninfected controls. The PLWH group was stratified into three subgroups: HIV-only (<em>n</em> = 57), HIV with AIDS-defining cancer (ADC, <em>n</em> = 9), and HIV with NADC (<em>n</em> = 12). Quantitative polymerase chain reaction (qPCR) was used to measure the Relative Telomere Length (RTL), expressed as a T/S ratio. The mean RTL was significantly longer in PLWH (<em>p</em> = 0.0002) and in the HIV/Cancer group (<em>p</em> = 0.0125) than in the control group (<em>n</em> = 163). In addition, the mean RTL was significantly longer in the PLWH group with non-AIDS-defining cancers (NADCs) compared to the control group (<em>p</em> = 0.03). However, no statistical difference between the HIV-only versus the HIV/cancer groups concerning RTL was observed. PLWH with a longer time since diagnosis of HIV infection (>13 years) had a trend towards longer RTL, showing a borderline statistical significance (<em>p</em> = 0.06). Analysis by cancer type showed ADCs were mainly Kaposi’s sarcoma (44.5%) and cervical cancer (33.3%), while NADCs were most commonly anal cancer (25%) and breast cancer (16.7%). These findings support the thesis that long-term ART may be associated with telomere elongation in PLWH, challenging the general perception of telomere shortening in this population. The significantly longer RTL in the NADC group suggests that telomere elongation confers greater cellular replicative potential, which might contribute to the elevated cancer risk in PLWH.

Background/Objectives: Human papillomavirus (HPV) is a major cause of cervical, penile, anal, and oropharyngeal cancers. HPV vaccination is the most effective public health strategy for its prevention. Understanding the factors influencing vaccination intentions is critical for developing effective public health policies and improving population-level vaccine uptake. Therefore, in this scoping review, we aimed to examine HPV vaccination research conducted in Korea, identify common trends and gaps in study populations and influencing factors, and provide evidence-based recommendations for public health policies. Methods: We systematically searched four Korean databases—Research Information Sharing Service (RISS), DBpia, Korean Studies Information Service System (KISS), and National Digital Science Library (NDSL)—for studies published from their respective inception dates to January 2025, using “human papillomavirus,” “HPV,” “vaccination,” and “intention” as keywords. Thirty-six studies were ultimately included. Study characteristics, populations, theoretical frameworks, and key variables were extracted and analyzed using descriptive statistics and content analysis. Results: Of the included studies, 61.1% and 38.9% targeted vaccination-eligible individuals (adolescents and adults) and parents/guardians, respectively, with 50% focusing exclusively on women. The major factors influencing HPV vaccination intention were attitude (47.2%), subjective norms (38.9%), and perceived behavioral control (30.9%). Attitude and knowledge were critical for vaccination-eligible individuals (Direct group), whereas subjective norms were key for parents/guardians (Indirect group). Conclusions: Korean HPV vaccination intention research has predominantly focused on women and parents, with insufficient attention to adolescents and men. Public health strategies must employ multilevel interventions tailored to each group’s decision-making structures, including school-based programs for adolescents, gender-inclusive policies for men, and community-based approaches to address social norms among parents. These findings provide evidence for policy development aligned with the WHO cervical cancer elimination goals.

Based on evidence-based medicine, the National Health Commission (NHC) Clinical Practice Guidelines for Colorectal Cancer in China (2025 Edition) integrates international cutting-edge advances with clinical practice in China, further developing and expanding on previous editions. This article is an abbreviated version of the Guidelines, retaining the core diagnosis and treatment framework while highlighting newly added content such as "surgical treatment of anal canal cancer" and "new technologies and advances in diagnosis and treatment". It systematically summarizes the core points of five major sections-surgery, internal medicine, radiotherapy, imaging, and pathology-facilitating clinicians in quickly grasping the essence of the Guidelines and promoting the standardization, precision, and homogenization of colorectal cancer diagnosis and treatment.

Sexual Toxicity After Chemoradiation for Anal Cancer Among Men Who Have Sex With Men: A Mixed-Methods Analysis

Anal squamous cell carcinoma, caused by human papillomavirus disproportionately affects people living with HIV (PLWH), particularly gay, bisexual, and other men who have sex with men (GBM). New guidelines recommend screening and treatment of pre-cancerous lesions. We aimed to estimate anal cancer incidence by HIV status, sex, and GBM status in British Columbia, Canada. Using administrative health databases, we assessed anal cancer stratified by HIV-status, sex, and sexual orientation from 1990 to 2019. A phenotypic algorithm was used to classify GBM status. We evaluated the comparative incidence of anal cancer using Fine and Gray's competing risks sub-distribution hazards model. Hazard ratios were estimated and adjusted for age, healthcare utilization, urbanicity, and Charlson co-morbidity index. Among 571 anal cancer diagnoses assessed, the incidence was highest among GBM with HIV (78.09 per 100,000 person-years [PY]; 95% confidence interval [CI] = 61.24-99.58) followed by heterosexual males with HIV (44.49 per 100,000 PY; 95% CI = 29.56-66.95), and females with HIV (12.05 per 100,000 PY; 95% CI = 4.52-32.11). GBM with HIV experience a 76-fold increased anal cancer risk compared with heterosexual men without HIV (aHR 76.08; 95% CI 55.14-104.97). There is an unmet need in anal cancer prevention among PLWH. Screening strategies that are sensitive, specific, acceptable, and cost-effective are necessary. This study provides the first population-based estimates of anal cancer incidence by HIV and GBM status in British Columbia, highlighting disparities and rising trends. These findings support prioritizing targeted screening programs and improving access to care.

Abstract BACKGROUND Recent data suggest that inflammatory bowel disease (IBD) in people living with HIV (PLWH) often follows a less aggressive course and is managed with fewer advanced therapies. Both HIV infection and IBD independently increase cancer risk, yet it is unclear whether the combined burden further amplifies that risk. METHODS We queried the U.S. TriNetX collaborative network (comprising >100 million patient records). Using ICD 10 codes, we identified Adults (≥18 y) with ≥3 IBD encounters who received an IBD therapy. We compared IBD in PLWH compared to IBD alone. A propensity score matching (PSM) was performed for age, sex, race, and key comorbidities. Outcomes included risks of colorectal or anal cancer, colorectal cancer alone, anal cancer, anal cancer or dysplasia, colectomy, and risk of skin cancers. Hazard ratios (HR) with corresponding 95% confidence intervals were estimated; P value < 0.05 suggested statistical significance. RESULTS After PSM, 1,329 patients were included in each group. The median follow-up duration was 3.9 years in the IBD-HIV cohort, compared to 4.4 years in the controls. HIV co-infection was not associated with higher hazards of combined colorectal or anal cancer (HR 1.30, 95% CI 0.84–2.03, p = 0.22) or colorectal cancer alone (HR 1.10, 0.68–1.78, p = 0.41). In contrast, anal cancer (HR 4.80, 1.82–12.61, p = < 0.001) and anal cancer or dysplasia risks (HR 11.54, 6.53–20.39, p = 0.007) were markedly increased. Colectomy occurred less often with HIV (HR 0.52, 0.32–0.85, p = 0.008). Cutaneous melanoma/skin cancer was not different between the groups (HR 1.43, 0.92–2.23, p = 0.63). CONCLUSION In this large, matched cohort, HIV did not increase colorectal cancer risk in IBD but was strongly associated with anal cancer and anal dysplasia while appearing protective against colectomy. These findings argue for better screening strategies in PLWH with IBD while maintaining standard colorectal dysplasia screening. Prospective studies are needed to clarify the mechanisms underlying these observations and to verify whether the relatively milder IBD course activity in PLWH persists long term. Limitations of this study include the retrospective nature, reliance on ICD codes, and potential for residual confounding. Thus, further research is warranted to validate these findings.

Proton therapy (PT) offers dosimetric advantages over conventional X-ray-based radiotherapy (XRT), aiming to reduce toxicity and better spare healthy tissues. The Agency for Health Quality and Assessment of Catalonia (AQuAS), commissioned by the Spanish Ministry of Health, conducted a Health Technology Assessment to evaluate the safety and clinical effectiveness of PT for cancer indications not yet approved for PT in Spain. This article summarizes the main findings regarding PT's safety and clinical performance in adults compared with XRT. The assessment was based on a systematic review of primary studies published between 2012 and 2024, following Cochrane methodological standards, PRISMA guidelines, and the GRADE approach. Eligibility criteria were defined using the PICO-DT framework, focusing on adult cancer patients, comparative study designs, and primary outcomes including serious adverse events, mortality, overall survival, and progression-free survival. Risk of bias was evaluated with RoB 2.0 and ROBINS-I depending on study design. Searches covered major biomedical databases. Of 6958 records screened, 76 were included (five randomized trials and 71 observational studies) across 16 tumour types. Overall, evidence certainty was low or very low, limited by few randomized trials, methodological concerns, and heterogeneity. For some indications, including leptomeningeal metastases, lung cancer, and anal cancer, evidence suggests that PT may be equivalent or superior to XRT, although certainty remains limited. PT shows variable, cancer-specific results and does not consistently outperform XRT. Some indications appear promising, but substantial evidence gaps persist, emphasizing the need for high-quality comparative studies and systematic clinical data collection.

Induction chemotherapy followed by chemoradiotherapy in patients with locally advanced anal cancers: The PRODIGE 85-FFCD 1804-KANALRAD trial.

Objectives: Among people with HIV (PWH), the epidemiology of malignant tumors has shifted from AIDS-defining malignancies (ADMs) to non-AIDS-defining malignancies (NADMs). This study examined temporal changes in the standardized incidence ratio (SIR) of malignant tumors in an HIV cohort in Japan. Methods: A retrospective cohort study was conducted of 3793 men treated for HIV at Osaka National Hospital between 2007 and 2024. Diagnoses of malignant tumors were identified from medical records and the expected numbers of cases were calculated using cancer incidence rates for the general male population of Japan. SIRs and 95% confidence intervals (CIs) were calculated and temporal changes across four periods (2007-2011, 2012-2016, 2017-2020, and 2021-2024) were evaluated using the p for trend. Results: The overall SIR for malignant tumors decreased from 5.12 (95% CI: 4.02-6.43) in 2007-2011 to 0.86 (95% CI: 0.64-1.14) in 2021-2024, mainly owing to a decline in ADMs (SIR: 111.93 to 5.70), including Kaposi's sarcoma (SIR: 4269.39 to 547.26) and AIDS-related lymphoma (SIR: 62.18 to 3.13). The overall SIR for NADMs was similar to that of the general population (1.04; 95% CI: 0.89-1.22), and decreased from 1.64 to 0.69, but the risks of anal cancer (SIR 40.63) and oral/pharyngeal cancer (SIR 3.16) remained high. Conclusions: Among men with HIV in Japan, the overall risk of ADMs and NADMs has decreased; however, the risk of specific NADMs remains high. Cancer prevention strategies for PWH need to focus on high-risk NADMs.

BackgroundAnal cancer incidence is increasing in the United States with an estimated 9,540 new cases in 2024. People with HIV (PWH) face the highest risk. The ANCHOR trial demonstrated that treating high-grade squamous intraepithelial lesions (HGSIL) in PWH significantly reduces anal cancer risk compared to controls. Screening with anal cytology (Pap smear) and high-resolution anoscopy (HRA), when indicated, is recommended for PWH but remains inadequate globally, including in the US. This study evaluates anal cancer screening in a region where HRA access requires at least one-hour travel.Figure 1.Percentages of Anal Pap Smears Recommended and PerformedSexual orientation influences whether an anal Pap smear is recommended and performed.Figure 2.Anal Pap Smear ResultsMost individuals had negative anal Pap smear results, but this difference did not reach statistical significance (p value = 0.171).MethodsThis retrospective study included two Ryan White-funded HIV clinics in Tucson, Arizona. Eligible participants, based on International Anal Neoplasia Society guidelines, were men who have sex with men (MSM) and transgender women (TGW) aged 35–75, and heterosexual men and women aged 45–75, with at least one clinical encounter between March 1, 2022, and January 14, 2025, and an anal Pap smear performed. Charts from five of twelve providers who reported not performing anal Paps were excluded. Proportions were compared using chi-square or Fisher’s exact tests, as appropriate.Figure 3.Percentages of HRA Recommended and Performed38.5% of individuals who were recommended HRA had it performed.Figure 4.HRA vs Anal Pap Smear ResultsAnal Pap results did not predict HRA results.ResultsOf 377 eligible individuals, 266 (70.6%) were MSM, 58 (15.4%) heterosexual men, 48 (12.7%) women, 4 (1.1%) TGW, and 1 (0.3%) transgender man. Anal Paps were recommended for 174/270 (64.4%) MSM and TGW and performed in 128 (47.4%) compared to lower rates in other groups (p value < 0.001) (Fig. 1). Most results were negative; atypical squamous cells of undetermined significance (ASCUS), with or without HPV, was the second most common finding (Fig. 2). No HGSIL was detected. Regardless of sexual orientation, 20/35 individuals underwent HRA when recommended (Fig. 3). Anal Pap results showed poor correlation with HRA findings (Fig. 4).ConclusionAnal cancer screening is challenging particularly when patients perceive their risk for anal cancer is low. Individuals at higher risk for anal cancer (MSM and TGW) were more likely to be recommended and pursue screening than heterosexual individuals. Ryan White funding, as we used, can help pay for HRA and transportation to it. However, local HRA, planned for Tucson in 2025, is needed to improve screening uptake and outcomes in all groups.DisclosuresAll Authors: No reported disclosures

In the previously completed NCI9673 (part A) single-arm study, the antiprogrammed death (PD)-ligand-1 antibody nivolumab demonstrated efficacy for patients with metastatic anal cancer. In NCI9673 (Part B), we evaluated the anticytotoxic T-cell lymphocyte antigen-4 (CTLA-4) antibody ipilimumab in combination with nivolumab for patients with incurable anal cancer. In this phase II NCI ETCTN trial, 100 patients with refractory, incurable anal cancer were randomly assigned to receive nivolumab (480 mg IV once every 4 weeks) alone or with ipilimumab (1 mg/kg IV once every 8 weeks). The primary end point was progression-free survival (PFS). Secondary endpoints included radiographic response, overall survival (OS), and grade ≥3 adverse events. A log-rank test was used to compare survival between arms, with a one-sided alpha of 0.1 and power of 90%. Immune biomarkers were analyzed from baseline and on treatment tissue and blood collections. The median PFS for nivolumab versus nivolumab plus ipilimumab were 2.9 months (90% CI, 1.9 to 3.8) and 3.7 months (90% CI, 2.0 to 5.6), respectively (hazard ratio [HR], 0.86 [95% CI, 0.60 to 1.23]; P = .25). Response rates were similar for nivolumab (17.4%) and nivolumab plus ipilimumab (21.5%; P = .89). The median OS was 15.9 months for nivolumab and 20.0 months for nivolumab plus ipilimumab (HR, 0.98 [90% CI, 0.63 to 1.51]). Grade ≥3 treatment-related AEs occurred in 6 patients (12%) receiving nivolumab alone and in 12 patients (25%) receiving nivolumab plus ipilimumab. At week 9, circulating TIGIT+ CD8+ cells (P < .001) increased with nivolumab plus ipilimumab treatment relative to baseline. The addition of ipilimumab to nivolumab did not statistically improve overall response rate, PFS, or OS but may harbor increased toxicity. Paired blood samples identified TIGIT expression on peripheral T cells as a compensatory change unique to dual PD-1 plus CTLA-4 blockade.

Human Papilloma Virus (HPV) is a causative agent in several cancers including cervical cancer, head and neck cancer, anal cancer, penile, vulvar and vaginal cancers. HPV through its virus-encoded protein E6 and the cellular E6-Associated Protein (E6-AP) target the tumor suppressor p53 protein for degradation thereby contributing to cancer development after HPV infection. As viruses cause cancer, the author previously hypothesized that SARS-COV-2 virus may be associated with cancer. More recent insights on the present hypothesis have come from studies suggesting (1) Spike protein of SARS-COV-2 may suppress p53 function, (2) cancer has been associated with mRNA vaccines that produce Spike, and (3) a case mentioned by Dr. Patrick Soon Shiong of a patient who survived HPV-associated head and neck cancer, but the tumor recurred after COVID mRNA vaccination including with liver metastases. Thus, the present hypothesis is that virally encoded proteins such as HPV-E6 or SARS-COV-2 Spike may cooperate in suppressing host defenses including tumor suppressor mechanisms involving p53. The hypothesis can be further explored through epidemiologic and laboratory studies.

Systemic complement protein levels as biomarkers of chemoradiotherapy response in anal squamous cell carcinoma.

Pelvic exenteration (PE) is the only curative option for extensive pelvic cancers. Advances have facilitated increasingly complex resectional and reconstructive components, including per-operative oncological adjuncts such as intraoperative radiotherapy. Cumulatively, these components increase operative duration beyond what is feasible within a single conventional operating day. Two-day/two-stage PE addresses this, but little is known about this approach. This study aims to evaluate the feasibility, safety and medium-term outcomes of a two-day/two-stage PE. Consecutive patients (2010-2025) from a prospectively maintained high-volume PE unit database (n = 373) undergoing two-day/two-stage PE were compared against a matched control cohort of single-day cases lasting ≥15 h. EQ5D-5L and decision regret scores were longitudinally collected after 2021. Surgical, oncological and health-related quality-of-life outcomes were evaluated. Twenty-seven patients underwent two-day/two-stage PE, and 38 had one-day PE; more anal cancers were in the two-day/two-stage group (p = 0.012); median follow-up was 24.2 months. No 90-day mortalities occurred; 3-year overall survival was 54.4% for two-day/two-stage PE and 70.5% for one-day PE (p = 0.31); and R0-resection rates were 82% and 76%, respectively (p = 0.76). Major morbidity occurred in 56% and 47% (p = 0.62), with a median length of stay of 37 and 27 days (p = 0.07) and intensive care days of 5 and 3 (p = 0.08). 12-month EQ5D-5L utility scores were 0.79 and 0.81 (p = 0.96), with low 12-month decision regret in both groups (p = 0.15). Two-day/two-stage PE is safe and feasible, potentially representing the only option for highly selected patients needing high-complexity PE with multiple components. Although equivalent R0-resections were obtained, medium-term oncological outcomes were poorer in patients undergoing two-day/two-stage interventions.

Anal cancer mortality has increased across high-income countries, yet subnational patterns remain poorly characterized. This study provides the first comprehensive, sex-stratified, spatiotemporal analysis of anal cancer (ICD-10 C21) mortality in Spain from 1999 to 2023. We conducted an ecological, descriptive, province-level analysis of mortality using data from the National Institute of Statistics. Sex-stratified Bayesian hierarchical models were applied to estimate smoothed relative risks (RRs) by province and year, incorporating spatial, temporal, and interaction effects. Model selection was guided by the Deviance Information Criterion and Widely Applicable Information Criterion. Posterior probabilities (PP) were used to identify high-risk provinces (PP > 0.95). Among 160 candidate models, optimal structures differed by sex: males showed intrinsic Conditional Autoregressive (iCAR) spatial prior with RW1 temporal prior and Type IV interaction; females showed iCAR with RW2 temporal prior and Type III interaction. Mortality rose in both sexes: male RR increased steadily to 1.39 in 2023; female RR followed a nonlinear trajectory with delayed surge to 1.30. Variance decomposition indicated male mortality was mainly temporal (80.2%), female mortality largely spatial (58.1%). Male hotspots clustered in southern/insular provinces (e.g., Las Palmas RR=1.22, Cádiz 1.18, Valencia 1.18); female hotspots were more dispersed (e.g., Las Palmas 1.34, Málaga 1.33, Barcelona 1.26). Anal cancer mortality in Spain is rising, revealing persistent sex-specific and geographic inequalities beyond national temporal trends. Precision prevention-via gender-neutral HPV vaccination, targeted screening, and prioritization of hotspot provinces-is urgently needed.

Objectives: Human papillomavirus (HPV) is an infectious disease transmitted sexually. It is the direct cause of cervical cancer, and it incriminates in oropharyngeal, anal, and genital cancers. Vaccination is the main control measure to exclude infection. Awareness and knowledge regarding HPV in Saudi Arabia still need improvement. Vaccination acceptance suffers from some hesitancy. This systematic review aimed to assess awareness and knowledge of HPV and HPV vaccine among young adults (18–30 years) and evaluate obstacles that prevent vaccination. Methods: According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses principles, a systematic search strategy was constructed through PubMed, Science Direct, Google Scholar, Scopus, and Web of Science. The search involved studies published between January 2020 and June 2025. Cross-sectional and quantitative studies that evaluate HPV and HPV vaccine among young adults (18–30) in Saudi Arabia were included. After completion of data extraction, selected studies were qualified to determine the level of bias. Results: Ten studies achieved the eligibility criteria; they showed a variable degree of awareness (43–59.6%) with sample sizes ranging from 114–580 respondents. A knowledge shortage regarding high-risk genotypes of HPV, modes of transmission, and vaccination was observed among medical students and the public. Barriers toward vaccination varied between lack of awareness, ignorance about the eligibility of the age of vaccination, and issues related to culture, with a noticeably higher degree of awareness among females than among males. Conclusion: Enhancement of education programs is needed; future investigations should be directed to improve the educational campaigns to promote public awareness of HPV. The development of the medical curriculum is a necessity.

Temporalities of interembodiment: Insights from clinical and community health practices.

ABSTRACT This study assessed the impact and cost-effectiveness of gender-neutral immunization with the nonavalent human papillomavirus (HPV) vaccine in South Korea. An established dynamic transmission model of HPV epidemiology was adapted to the South Korean population. Vaccinating both girls and boys with the nonavalent HPV vaccine was compared to the currently administered program of vaccinating girls only with the quadrivalent vaccine. Compared to vaccination of girls only with the quadrivalent HPV vaccine, gender-neutral vaccination with the nonavalent HPV vaccine was projected to prevent 1,282,415 cases of cervical intraepithelial neoplasia grade 1 (CIN1), 918,384 cases of CIN2/3, 36,248 cases of cervical cancer, and 9,313 cervical cancer deaths in females over 100 years. Gender-neutral vaccination was projected to reduce HPV-related vaginal, vulvar, anal, and head & neck cancers in females by 4.8–8.2%, in addition to reductions of 14.6% and 15.8% in genital warts and recurrent respiratory papillomatosis, respectively. In males, gender-neutral vaccination was projected to prevent 666,182 cases of genital warts, 7,422 cases of RRP, 995 cases of anal cancer, 2,441 cases of head & neck cancer, and 122 cases of penile cancer. The incremental cost-effectiveness ratio (ICER) was ₩38.9 million per quality-adjusted life year (QALY), which is below the accepted cost-effectiveness threshold in South Korea. These findings suggest that gender-neutral vaccination with the nonavalent HPV vaccine would reduce the public health burden of HPV disease in both females and males in South Korea and would be cost-effective under base case assumptions about vaccine price and coverage of boys.

The National Health Commission of the People's Republic of China Guidelines for Diagnosis and Treatment of Colorectal Cancer (2025 edition), based on evidence-based medicine, integrates cutting-edge international advances with Chinese clinical practice, and supplements and completes the previous versions. This version of the guidelines, retains the core diagnostic and treatment framework, highlights new contents such as "Surgical treatment of anal canal cancer" and "New technologies and advances in diagnosis and treatment", and systematically summarizes the core points in the surgical treatment, medical oncology treatment, radiation oncology treatment, imaging, and pathology treatment. It is designed to help clinicians quickly grasp the key points of the guidelines and promote the standardization, precision, and consistence of colorectal cancer diagnosis and treatment.

Anal gland adenocarcinoma is an extremely rare malignancy, with squamous cell carcinoma being the most common type of anal canal cancer. Due to its rarity, there are no well-defined diagnostic criteria or standardized treatment protocols for this condition. This study describes a rare instance of adenocarcinoma in the anal canal, which initially manifested as an anal fistula. The patient received a multifaceted treatment plan encompassing surgical intervention, chemotherapy, and radiotherapy. The study investigates the methods of diagnosis, characteristics of tumours, and the selected treatment approach. This case highlights the challenges in diagnosing and managing anal canal adenocarcinoma. Given its rarity, further studies are needed to establish standardized diagnostic and treatment guidelines.