Search Results (235)

Human papillomavirus (HPV) significantly contributes to anogenital cancers, with elevated risks among people living with HIV (PWH), particularly men who have sex with men (MSM). This study assessed anal HPV prevalence and associated risk factors in PWH in Mexico, focusing on the role of antiretroviral therapy (ART). Methods: A cross-sectional study at an HIV clinic in Mexico City (October 2023–December 2024) enrolled 214 MSM with HIV. The participants completed a validated risk factor questionnaire and provided anal samples for real-time PCR testing of 28 HPV genotypes. Logistic regression analyzed associations between HPV infection, ART regimens, and clinical/behavioral factors. Results: HPV prevalence was 89.3%, with HPV-16 (20.1%) being the most common high-risk genotype. Integrase inhibitor (INSTI) use was inversely associated with HPV-16 infection (OR: 0.42; 95% CI: 0.21–0.83; p = 0.011), while protease inhibitor use increased HPV-16 (OR: 2.16; 95% CI: 1.09–4.29; p = 0.025) and HPV-6 risks. Higher CD4+ counts (≥500 cells/mm³) and undetectable HIV viral load (<40 copies/mL) were protective against multiple HPV genotypes. Lower education and smoking increased HPV risk. Conclusions: This first Mexican study in the ART and HPV vaccination era highlights high anal HPV prevalence in PWH and suggests that INSTI-based regimens may reduce HPV-16 risk, informing ART selection for HPV prevention. Full article

Anal cancer is a rare malignancy with rising incidence. Definitive treatment with radiation and concurrent chemotherapy represent the standard of care for patients with non-metastatic disease. Advances in radiation delivery through the use of intensity-modulated radiotherapy have significantly reduced the toxic effects of treatment. Adaptive radiotherapy (ART) has emerged as a strategy to further enhance treatment precision and individualize therapy in response to patient-specific changes during the course of chemoradiotherapy. The rationale for ART in anal cancer stems from the recognition that significant anatomic and tumor changes can occur throughout the 5–6-week treatment course, including tumor shrinkage, weight loss, and variable rectal/bladder filling. This review discusses the role of ART in contemporary anal cancer management. We overview the principles of ART, delineate the technical workflows (including both computed tomography (CT) and MR-guided approaches), and examine how adaptive techniques are applied in treatment planning and delivery. We also review the clinical evidence to date, including dosimetric studies and emerging clinical trial data on ART in anal cancer, particularly its impact on outcomes and toxicity. Full article

Background: Infectious proctitis remains an underrecognized entity, although sexually transmitted diseases, especially bacterial infections, exhibit a marked increase in their incidence. Methods: Here, we report a case of a 44-year-old man who presented to the emergency department with lower abdominal and rectal pain, tenesmus, fever and night sweats for the past 6 days. Results: The computed tomography initially revealed a high suspicion of metastatic rectal cancer. The endoscopic findings showed a 5 cm rectal mass, suggestive of malignancy. The histologic examination showed, however, no signs of malignancy and lacked the classical features of an inflammatory bowel disease, so an infectious proctitis was further suspected. The patient reported to have had unprotected receptive anal intercourse, was tested positive for Treponema pallidum serology and received three doses of intramuscular benzathine penicillin G. A control rectosigmoidoscopy, imaging at 3 months and histological evaluation after antibiotic treatment showed a complete resolution of inflammation. Conclusions: Syphilitic proctitis may mimic various conditions such as rectal cancer or inflammatory bowel disease and requires a high degree of suspicion. Clinicians need to be aware of infectious proctitis in high-risk populations, while an appropriate thorough medical history may guide the initial diagnostic steps. Full article

Background: Human papillomavirus (HPV) is the most common sexually transmitted infection in the United States (U.S.) and a major contributor to several cancers, including cervical, anal, penile, and oropharyngeal cancers. Although a safe and effective vaccine is available, HPV vaccination rates remain suboptimal, particularly among racial, ethnic, and immigrant minority groups. This study explored multiple factors, such as cultural, social, and structural influences, influencing HPV vaccine decision-making among Cape Verdean immigrant parents in the U.S., a population currently underrepresented in HPV research. Methods: Qualitative study using individual, in-depth interviews with Cape Verdean immigrant parents of children aged 11 to 17 years living in the U.S. Interviews were transcribed verbatim and analyzed thematically using the social ecological model (SEM) to identify barriers and facilitators at the intrapersonal, interpersonal, organizational, community, and policy levels. Results: Forty-five Cape Verdean parents (27 mothers, 18 fathers) participated. Fathers were significantly older than mothers (50.0 vs. 41.1 years, p = 0.05). Most were married or partnered (60%), had at least a high school education (84.4%), and reported annual household incomes of US$50,000 or more (66.7%), with no significant gender differences. Nearly all spoke Creole at home (95.6%). Fathers had lower acculturation than mothers (p = 0.05), reflecting less adaptation to U.S. norms and language use. Most parents had limited knowledge of HPV and the vaccine, with gendered beliefs and misconceptions about risk. Only seven mothers (25.9%) reported receiving a provider recommendation; all indicated that their children had initiated vaccination (1 dose or more). Mothers were the primary decision-makers, though joint decision-making was common. Trust in providers was high, but poor communication and the lack of culturally and linguistically appropriate materials limited informed decision-making. Stigma, misinformation, and cultural taboos restricted open dialogue. Trusted sources of information included schools, churches, and Cape Verdean organizations. While parents valued the U.S. healthcare system, they noted gaps in public health messaging and provider engagement. Conclusions: Findings revealed that HPV vaccine uptake and hesitancy among Cape Verdean immigrant parents in the U.S. were influenced by individual beliefs, family dynamics, healthcare provider interactions, cultural norms, and structural barriers. These findings highlight the need for multilevel strategies such as culturally tailored education, community engagement, and improved provider communication to support informed vaccination decisions in this population. Full article

Background: Pathological complete response (pCR) following neoadjuvant therapy and surgery for locally advanced rectal cancer is associated with improved prognosis. Accurately predicting who will achieve pCR could theoretically eliminate the need for surgery for these patients. We aimed to compare pCR and non-pCR rectal cancer patients following neoadjuvant therapy, searching for clinical predictors for pCR and comparing oncological outcomes between these groups. Methods: This is a single-center retrospective analysis of all patients who underwent a curative-intent rectal resection between 2010 and 2020 for primary non-metastatic rectal cancer following neoadjuvant therapy. The cohort (263 patients) was divided into two groups according to the pathological results from surgery: the pCR group (53 patients) and the non-pCR group (210 patients). Results: The groups were similar in terms of baseline characteristics, clinical presentation, and staging, but tumors of the pCR group were significantly higher in the rectum (mean distance from the anal verge 7.92 cm versus 6.9 cm respectively, p = 0.04), and more of them were located at the posterior rectal wall (37.7% versus 24.3%, p = 0.049). Multivariate analysis found posterior location and tumor height to be significantly associated with pCR (OR 2.23, 95% CI 1.11–4.45, p = 0.023), (OR 1.14, 95% CI 1.03–1.27, p = 0.015). The 5-year overall survival was 95.6% in the pCR group compared with 87.5% in the non-pCR group (p = 0.09), and the 5-year disease-free survival was 92.7% versus 64.5%, respectively (p < 0.001). Conclusions: Tumor location at the posterior wall of the rectum and higher tumor location were found to be associated with pCR. Patients achieving pCR demonstrate improved prognosis compared with non-pCR patients. Full article

Human papillomavirus (HPV) is a leading cause of several cancers, most notably cervical cancer, but also anal, penile, vulvar, vaginal, and oropharyngeal malignancies. While vaccines and screening technologies offer highly effective prevention, the global burden of HPV-induced cancers remains disproportionately high in low- and middle-income countries (LMICs). This literature review provides a comprehensive synthesis of the types, mechanisms, treatments, and prevention strategies associated with HPV-related cancers, while also highlighting regional disparities in healthcare access and infrastructure. It critically examines the barriers LMICs face in adopting life-saving interventions, such as limited healthcare infrastructure, vaccine hesitancy, funding gaps, and cultural stigma. The review further explores recent scientific and policy advances—including single-dose vaccination, self-sampling HPV tests, and senolytic therapies—that have the potential to reduce global health inequities. By connecting molecular biology with public health systems, this paper underscores the need for interdisciplinary solutions and equity-centered approaches to combat HPV-induced cancers worldwide. The findings emphasize that eliminating cervical cancer and other HPV-related diseases is not only a scientific goal but also a moral imperative requiring global collaboration and local action. Full article

Introduction: Anal squamous cell carcinoma (ASCC) is a rare but increasingly common gastrointestinal malignancy, mainly associated with oncogenic human papillomaviruses (HPVs). The role of non-coding RNAs (ncRNAs) in tumorigenesis is recognized, but the impact of viral ncRNAs on host gene expression remains unclear. Methods: We re-analyzed total RNA-Seq data from 70 anal biopsies: 31 low-grade squamous intraepithelial lesions (LGSIL), 16 high-grade SIL (HGSIL), and 23 ASCC cases. Microbial composition was assessed taxonomically. Novel viral miRNAs were predicted using vsRNAfinder and linked to host targets using TargetScan and expression correlation analyses. Results: Microbial profiling revealed significant differences in abundance, with Alphapapillomaviruses types 9, 10, and 14 enriched across lesion grades. We identified 90 novel viral miRNAs and 177 significant anti-correlated miRNA–mRNA interactions. Target genes were enriched in pathways related to cell cycle, epithelial–mesenchymal transition, lipid metabolism, immune modulation, and viral replication. Discussion: Our findings suggest that HPV-derived miRNAs, including those from low-risk types, may contribute to neoplastic transformation by modulating host regulatory networks. Conclusion: This study highlights viral miRNAs as potential drivers of HPV-related anal cancer and supports their utility as early biomarkers and therapeutic targets in ASCC. Full article

Radical chemoradiotherapy has been used as a frontline treatment for squamous cell cancer of the anus for the last 30–40 years. Considerable acute and chronic adverse effects have been observed following radiotherapy using 2D and 3D techniques. A case of very late-onset severe chronic toxicity in a patient 26 years after radiotherapy is presented. The patient underwent radical chemoradiotherapy for squamous anal cancer stage T3N3M0 in 1998. In the anal region, cumulative doses up to 77.6 Gy (including electron boost) were administered. Durable complete regression of the disease was achieved. Fourteen years after treatment, the patient developed vast fibroatrophy of the anus and perineum, progressing within the subsequent four years to necrosis and sphincter loss. Twenty years after treatment, the asymptomatic osteonecrotic foci in the left femur appeared on MRI scans. Despite two courses of hyperbaric oxygen treatment, the fibroatrophy and subsequent necrosis of soft tissues remained progressive, but the osteonecrosis was stable. Twenty-six years after treatment, the progressive changes induced symptomatic osteomyelitis of the ischium and pubic bone. The patient now requires permanent supportive treatment. The presented case is exceptional in the very late-onset typical chronic adverse effects developing after non-conformal radiotherapy administered at high doses as part of contemporary treatment protocols. There is little evidence regarding the late onset of chronic adverse effects, since the follow-up period is usually shorter than that of the case presented. Moreover, a significant portion of patients do not survive to reach the late-onset period of adverse effects. The presented case shows that there may be long-term survivors of anal cancer in the population who were treated with outdated techniques and who still carry a risk of late-onset severe, progressive adverse effects. Full article

Human papillomaviruses (HPVs), like many other viruses, are able to integrate their genomes into the host cellular genome. This integration can activate viral oncogenes or alter the function of cellular oncogenes and tumor suppressor genes, thereby increasing the likelihood of HPV-associated tumor development. In particular, HPV types 16 and 18 are responsible for over 70% of all cervical, anal, and oropharyngeal cancers worldwide, with rising incidence. Even more, high-resolution mapping of preferred integration sites using LR-Seq technologies offers deep insights into the molecular mechanisms of HPV integration. LR-Seq enables the detection of complex integration patterns, where the viral genome can be replicated and amplified into virus–host concatemers, including events within large structural variations or highly repetitive genomic regions. Furthermore, aligning LR-Seq data to the latest T2T reference genome (hs1) is necessary to provide new information about viral integration in genomic regions that were previously inaccessible, such as centromeres and other structurally complex repeat-rich loci. In this review, we provide insights into HPV genomic integration revealed by LR-Seq technologies, with a particular focus on how the use of the complete T2T reference genome enhances the detection of integration events in previously uncharacterized, repeat-rich regions of the human genome. Full article

Background: Anal cancer screening has allowed for the diagnosis of early-stage anal cancers; however, guidelines for the treatment of early anal cancers remain mixed given the scarcity of clinical trials and data. Management ranges from chemoradiation therapy to local surgical excision. Methods: This paper’s objective is to clarify the definition of early anal cancer and its management. Approval for this systematic review was obtained through PROSPERO [CRD42022304327]. Three independent reviewers screened the studies and performed data analysis, with conflicts resolved by a fourth reviewer. All information is presented according to the Preferred Reporting Item for Systematic Reviews and Meta-Analysis (PRISMA). The Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) criteria were used to assess the certainty of the evidence. Results: The MEDLINE, EMBASE and Cochrane databases were queried with 628 articles screened. A total of 15 articles were selected for inclusion. Early anal cancer was most often defined as T1-2N0M0 anal cancer but also included Superficially Invasive Squamous Cell Carcinoma (SISCCA). There were various treatments assessed for outcomes including local excision, chemoradiation, and radiation. The studies reported overall survival, cancer-specific survival, recurrence-free survival, and/or colostomy-free survival, leading to significant heterogeneity amongst the studies. No meta-analysis was possible. Conclusions: Poor-quality studies exist for the evaluation of the most effective treatment modality for early anal cancer. Surgical excision alone with adequate margins has equivocal results, but data is poor. Chemoradiation is successful but may be overtreatment. Randomized controlled studies are needed, as screening will result in earlier anal cancer diagnoses. Full article

While locally advanced rectal cancer is the first clinical suspicion for severe rectal stenosis, in extremely unusual cases a lower bowel obstruction may be related to bladder metastasis. We present the case of a 64-year-old male who was admitted for occlusive rectal tumor (4 cm from the anal verge), for which an emergency loop-colostomy was performed. After two inconclusive endoscopic biopsies, a transanal rectal tru-cut biopsy allowed for the detection of high-grade urothelial carcinoma with signet ring cells. Furthermore, primary origin was detected in a small bladder tumor. In imaging reassessment after neoadjuvant chemotherapy, regression of the lesions both from the bladder and rectum was observed. Radical surgery with total pelvic exenteration was considered in the absence of other secondary tumors, but the patient declined and continued with radiotherapy. Subsequently he developed malignant chylous ascites and unfortunately died three months later. Reviewing the literature, we found twenty-five cases of urothelial metastasis to the rectum, originating from the bladder, including this newly present case. Rectal metastasis of urothelial origin poses a two-fold challenge in terms of both diagnosis and treatment. Determining the specific features of this uncommon manifestation of a common disease will improve future approaches. Full article

Background/Objectives: The improved long-term survival of rectal cancer patients has led to a major increase in the prevalence of functional complications. Understanding which patients are prone to develop major LARS is important for their preoperative counselling and follow-up. Herein, we aimed to assess the risk factors for LARS. Methods: This is a retrospective cohort study on rectal cancer patients. All patient and tumour variables, management plan, type of neoadjuvant therapy, radiation dose to anal sphincter, and perioperative outcomes were collected from the hospital electronic databases. We quantified LARS and compared the score before and after surgery (mean follow-up of 42.2 ± 32 months). Results: A total of 182 patients were included for the final analysis. LARS was present in 43.4% (n = 79) of patients, with 14.8% (n = 27) having minor LARS and 28.5% (n = 52) having major LARS. Age (p = 0.03), male gender (p < 0.00001), smoking (p = 0.04), neoadjuvant radiotherapy (p = 0.02), rectal stump length (p = 0.008), end-to-end anastomosis (p = 0.008), and ileostomy (p = 0.002) were found to significantly increase the rate of LARS. A logistic regression model based on the above variables was able to predict major LARS with good predictive value (AUC 0.700). Conclusions: LARS is highly common after sphincter-preserving surgery, and it is significantly more common in young, male patients with a history of smoking, having mid-lower rectal cancers with neoadjuvant radiotherapy, and undergoing TME surgery with end-to-end low anastomosis and ileostomy. Full article

Anal cancer is a rare diagnosis, but incidence has been increasing over the past decade. Anal cancer is associated with the human papilloma virus (HPV), specifically the high-risk subtypes of 16 and 18. In addition, the precursor lesion for anal cancer is high-grade squamous intraepithelial lesions (HSILs) and its treatment and surveillance has been emphasized over the last 5 years. The current standard of care for anal cancer includes the Nigro protocol, concurrent chemoradiation, typically radiation with systemic mitomycin and 5-fluorouracil (5-FU). The protocol’s efficacy laid the foundation for sphincter preservation and non-operative management. This review will detail the essential clinical trials in the treatment and surveillance of premalignant lesions and anal squamous cell cancer, including alterations in radiation dosing, systemic chemotherapy, and immunotherapy over the last several decades. Full article

Inflammatory bowel disease (IBD), comprising ulcerative colitis (UC) and Crohn’s disease (CD), is a chronic condition marked by persistent intestinal inflammation of unknown etiology. Disease onset involves genetic predisposition and environmental factors that disrupt the intestinal immune homeostasis. The intestinal microbiome and immune response play pivotal roles in disease progression. Advances in molecular therapies and early interventions have reduced surgery rates; however, colorectal cancer (CRC) remains a significant concern, driven by chronic inflammation. In UC, the risk of UC-associated neoplasia (UCAN) increases with disease duration, while CD patients face elevated risks of small intestine, anal fistula, and anal canal cancers. Endoscopic surveillance is advised for UCAN, but optimal screening intervals remain undefined, and no established guidelines exist for CD-associated cancers. UCAN morphology often complicates detection due to its flat, inflammation-blended appearance, which differs pathologically from sporadic CRC (sCRC). UCAN is frequently surrounded by dysplasia, with p53 mutations evident at the dysplasia stage. IBD-associated gastrointestinal cancers exemplify inflammation-driven carcinogenesis with distinct molecular mechanisms from the adenoma-carcinoma sequence. This review explores the epidemiology, risk factors, clinical and pathological features, current surveillance practices, and molecular pathways underlying inflammation-associated cancers in IBD. Full article

The impact of the microbiota on radiation (RT)-induced toxicity and cancer response to radiotherapy is an emerging area of interest. In this review, we summarize the available preclinical and clinical evidence concerning microbiota modulation of RT toxicity and efficacy in the main gastrointestinal (GI) districts. A huge amount of data supports the clinical application of microbiota modulation, particularly through prebiotics and probiotics, to prevent or mitigate radiotherapy-induced toxicity in rectal cancer. Preclinical and clinical studies also support the observation of microbiota modulation to impact the toxicity and efficacy of treatment in esophageal cancer, hepatocellular carcinoma (HCC), and anal squamous cell carcinoma (ASCC). However, insufficient evidence remains to endorse microbiota modulation as a strategy to enhance tumor radiosensitivity in clinical practice. Well-designed studies focusing on prebiotics, probiotics, and fecal microbiota transplantation are needed across all GI sites to evaluate their potential to improve treatment efficacy, as suggested by promising preclinical findings. The impact of pre-treatment microbiota analyses should be addressed in prospective studies to verify the efficacy of patient-level tailored strategies. Additionally, the repurposing of radioprotective agents with innovative delivery systems, such as encapsulated amifostine, holds significant promise for mitigating small bowel toxicity, thereby enabling more effective RT treatment. Full article