The unique case study presented here explores an exceptionally rare occurrence in an HIV-positive female-synchronous diagnoses of anal squamous cell carcinoma and diffuse large B cell lymphoma (DLBCL) of the stomach. With limited existing literature on such clinical scenarios, this case serves as an unprecedented insight into the complexities of managing such synchronous malignancies in HIV-positive patients. The article also examines the heightened risk of specific cancer types in individuals living with HIV compared to those without the virus, focusing on AIDS-defining cancers such as Kaposi sarcoma, various lymphomas (including Burkitt lymphoma, immunoblastic lymphoma, and primary central nervous system lymphoma), and invasive cervical cancer. Additionally, it highlights an increased incidence and severity of other cancers amongst HIV-positive individuals, including Hodgkin lymphoma, anal cancer, testicular cancer, melanoma, various skin and superficial eye cancers, and leiomyosarcoma. The article discusses the challenges in the treatment plan, the impact of HIV status on the patient\'s condition, and the evolving landscape of cancer risk in people living with HIV. Despite significant progress in HIV care, cancer remains a paramount health concern for this population, necessitating tailored approaches and further research to ensure improved outcomes for individuals facing this dual challenge. The case highlights the need for greater inclusivity of PLWH in cancer clinical trials and reinforces the importance of equitable cancer care for this unique patient demographic.

Immunotherapy has revolutionised cancer treatment over the past decade. Long-term durable responses can be achieved in some cancer patient populations that were previously facing terminal disease. In this chapter, we summarise current phase 3 clinical trial evidence for the use of immunotherapy in gastrointestinal cancers (oesophageal squamous cell carcinoma, oesophago-gastric adenocarcinoma, pancreatic cancer, biliary cancer, hepatocellular carcinoma, colorectal cancer, and squamous cell cancer of the anus). We discuss meaningful biomarkers used in clinical trials to select patients most likely to benefit from immunotherapy, such as mismatch-repair deficiency (MMRd)/microsatellite instability (MSI) and programmed-death-ligand-1 (PD-L1) immunohistochemistry (IHC) expression. Clinical questions are arising regarding the role of immunotherapy in the adjuvant/perioperative setting, optimal timing of surgery in patients who respond to immunotherapy, and toxicities specific to patients with gastrointestinal malignancies. We outline the current landscape and future horizon of immunotherapy in gastrointestinal cancers, such as strategies to increase effectiveness of checkpoint blockade through combinations with other checkpoint inhibitors, cytotoxic chemotherapy, targeted agents, radiotherapy, CAR-T therapy, and cancer vaccines.

BACKGROUND: The objectives were to evaluate the safety and immunogenicity of the nonavalent human papillomavirus (nHPV) vaccine in adult Spanish women living with HIV (WLHIV); the prevalence of anal and cervical dysplasia and nHPV vaccine genotypes in the anus and cervix; and risk factors for high-risk HPV (HR-HPV) infection in anal mucosa.
METHODS: In this single-center, open-arm, non-randomized clinical trial, the nHPV vaccine was administered at 0, 2, and 6 months to WLHIV enrolled between February 2020 and November 2023, measuring vaccine antibody titers pre-vaccination and at 2, 6, and 7 months after the first dose. Cervical and anal cytology and HPV PCR genotyping studies were performed. Women with abnormal cytology and/or anal or cervical HPV infection at baseline underwent high-resolution anoscopy and/or colposcopy.
RESULTS: A total of 122 participants were included with mean age of 49.6 years: 52.5% smoked; 10.7% had anal-genital condylomatosis; 38.5% were infected by HR-HPV in the anus and 25.4% in the cervix, most frequently HPV 16; 19.1% had anal intraepithelial neoplasia 1-(AIN1); and 3.1% had cervical intraepithelial neoplasia 1 and 2 (CIN1/CIN2). Vaccine administration did not modify viral-immunological status (CD4 [809 ± 226.8 cells/uL vs. 792.35 ± 349.95; p = 0.357]) or plasma HIV load (3.38 ± 4.41 vs. 1.62 ± 2.55 cop/uL [log]; p = 0.125). Anti-HPV antibodies ([IQR: 0-0] vs. 7.63 nm [IQR: 3.46-19.7]; p = 0.0001) and seroconversion rate (8.2% vs. 96.7% [p = 0.0001]) were increased at 7 versus 0 months. There were no severe vaccine-related adverse reactions; injection-site pain was reported by around half of the participants. HR-HPV infection in the anus was solely associated with a concomitant cervix infection (HR 5.027; 95% CI: 1.009-25.042).
CONCLUSIONS: nHPV vaccine in adult WLHIV is immunogenic and safe.

BACKGROUND: Managing patients with obstructing rectal cancer is challenging due to the risks of gastrointestinal obstruction and perforation. This study evaluates the outcomes of pre-emptive laparoscopic colostomy creation in patients with locally advanced rectal and anal cancer to prevent symptoms and facilitate therapy initiation.
METHODS: This retrospective cohort study includes patients with locally advanced rectal or anal cancer assessed by our Colorectal Multidisciplinary Team from January 2017 to February 2024. Patients who underwent pre-emptive laparoscopic colostomy were compared to a control group of non-obstructing rectal cancer patients who started direct oncological treatment. The primary endpoint was the time from diagnosis to the initiation of oncological treatments. The secondary endpoints were the rate and timing of subsequent radical resection, surgical morbidity and hospital stay. A Weibull regression was used to evaluate the time differences between the groups.
RESULTS: There were 37 patients who received pre-emptive laparoscopic colostomy, compared to 207 control patients. The mean time from diagnosis to the start of neoadjuvant therapy was 38.3 ± 2.3 days. Despite higher rates of malnutrition and more advanced stages in the colostomy group, no significant differences were observed in the time to start therapy (p = 0.083) or time to radical resection (p = 0.187) between the groups. The laparoscopic procedure showed low rates of postoperative complications and acceptable lengths of stay.
CONCLUSIONS: Pre-emptive laparoscopic colostomy is a feasible approach for managing obstructing rectal or anal cancer. Treatment timelines were not extended compared to timelines for non-obstructing cases, despite differences in nutritional status and staging. Further prospective studies with larger cohorts are needed to validate these findings and refine treatment protocols for obstructing gastrointestinal malignancies.

UNASSIGNED: Squamous cell carcinoma of the anus (SCCA) can recur after chemoradiotherapy (CRT). Early prediction of treatment response is crucial for individualising treatment. Existing data on radiological biomarkers is limited and contradictory. We performed an individual patient data meta-analysis (IPM) of four prospective trials investigating whether diffusion-weighted (DW) magnetic resonance imaging (MRI) in weeks two to three of CRT predicts treatment failure in SCCA.
UNASSIGNED: Individual patient data from four trials, including paired DW-MRI at baseline and during CRT, were combined into one dataset. The association between ADC volume histogram parameters and treatment failure (locoregional and any failure) was assessed using logistic regression. Pre-defined analysis included categorising patients into a change in the mean ADC of the delineated tumour volume above and below 20%.
UNASSIGNED: The study found that among all included 142 patients, 11.3 % (n = 16) had a locoregional treatment failure. An ADC mean change of <20 % and >20 % resulted in a locoregional failure rate of 16.7 % and 8.0 %, respectively. However, no other ADC-based histogram parameter was associated with locoregional or any treatment failure.
UNASSIGNED: DW-MRI standard parameters, as an isolated biomarker, were not found to be associated with increased odds of treatment failure in SCCA in this IPM. Radiological biomarker investigations involve multiple steps and can result in heterogeneous data. In future, it is crucial to include radiological biomarkers in large prospective trials to minimize heterogeneity and maximize learning.

High-risk human papillomavirus (HR-HPV) is associated with the development of different types of cancer, such as cervical, head and neck (including oral, laryngeal, and oropharyngeal), vulvar, vaginal, penile, and anal cancers. The progression of premalignant lesions to cancer depends on factors associated with the host cell and the different epithelia infected by HPV, such as basal cells of the flat epithelium and the cells of the squamocolumnar transformation zone (STZ) found in the uterine cervix and the anal canal, which is rich in heparan sulfate proteoglycans and integrin-like receptors. On the other hand, factors associated with the viral genotype, infection with multiple viruses, viral load, viral persistence, and type of integration determine the viral breakage pattern and the sites at which the virus integrates into the host cell genome (introns, exons, intergenic regions), inducing the loss of function of tumor suppressor genes and increasing oncogene expression. This review describes the role of viral integration and the molecular mechanisms induced by HR-HPV in different types of tissues. The purpose of this review is to identify the common factors associated with the role of integration events in the progression of premalignant lesions in different types of cancer.

Anal squamous cell carcinoma (ASCC) incidence is increasing globally. International consensus guidelines published in 2024 include HPV and/or cytology testing of anal swabs in those at greatest risk of ASCC. Self-collected anal swabs may be important for increasing screening uptake, but evidence is needed as to their equivalence to clinician-collected swabs. We searched Medline, Embase, Cochrane Library, and CINAHL databases for publications to 13 June 2023. Studies were included if reporting data on HPV testing, cytology testing, or acceptability, for both self- and clinician-collected anal swabs. Risk of bias was assessed using the QUADAS-2 assessment tool. The primary outcome was HPV and cytology sampling adequacy. Secondary outcomes were HPV and cytology results, and acceptability of collection methods. Thirteen papers describing 10 studies were eligible. Sample adequacy was comparable between self- and clinician-collected swabs for HPV testing (meta-adequacy ratio: 1.01 [95% CI 0.97-1.05]) but slightly lower for cytology by self-collection (meta-adequacy ratio: 0.91 [95% CI 0.88-0.95]). There was no significant difference in prevalence (meta-prevalence ratio: 0.83 (95% CI 0.65-1.07) for any HR-HPV, 0.98 (95% CI 0.84-1.14) for any HPV, and 0.68 (95% CI 0.33-1.37) for HPV16), or any cytological abnormality (meta-prevalence ratio 1.01 [95% CI 0.86-1.18]). Only three papers reported acceptability results. Findings indicate self-collection gives equivalent sample adequacy for HPV testing and ~ 10% inferior adequacy for cytological testing. Meta-prevalence was similar for HPV and cytology, but confidence intervals were wide. Larger studies are required to definitively assess use of self-collected swabs in anal cancer screening programs, including acceptability.

OBJECTIVE: To assess the risk and natural history of developing advanced anal disease after diagnosis of anal condyloma in people living with HIV (PLWH).
METHODS: This was a single-centre retrospective cohort study of PLWH and anal condyloma from 2001 to 2021. Patients who developed advanced anal disease (AAD; anal high-grade squamous intraepithelial lesions and/or anal cancer) were compared to those who did not progress (non-AAD). We assessed the potential association between AAD and condyloma location, recurrence, and treatment modality. AAD-free survival was calculated utilizing Kaplan-Meier methods.
RESULTS: A total of 118 PLWH and anal condyloma were included. Mean overall follow-up time was 9.3 years. A total of 31% of patients developed AAD (n = 37). Average time to AAD from condyloma diagnosis was 5.6 years. On multivariate analysis, risk for AAD development was associated with perianal location of condyloma (OR 4.39, p = 0.038) and increased time from initial condyloma diagnosis (OR 1.12, p = 0.008). Higher CD4/CD8 ratios were associated with lower risk of AAD (OR 0.15, p = 0.029). Condyloma recurrence and treatment type were not associated with development of AAD. AAD-free survival was longer in those with intra-anal only condyloma versus those with either perianal disease alone or combined intra-anal/perianal disease (mean survival times: 22.8 vs. 8.7 vs. 10.7 years, p = 0.017).
CONCLUSIONS: Our study demonstrates the need for careful, long-term follow-up of PLWH and condyloma, particularly in the setting of perianal disease and low CD4/CD8 ratio. Risk of anal disease progression is present even in the setting of condyloma regression following treatment.

The perianal disease affects up to one-third of individuals with Crohn\'s disease (CD), causing disabling symptoms and significant impairment in quality of life, particularly for those with perianal fistulising CD (PFCD). The collaborative effort between gastroenterologists and surgeons is essential for addressing PFCD to achieve fistula closure and promote luminal healing. Limited fistula healing rates with conventional therapies have prompted the emergence of new biological agents, endoscopic procedures and surgical techniques that show promising results. Among these, mesenchymal stem cells injection is a particularly hopeful therapy. In addition to the burden of fistulas, individuals with perianal CD may face an increased risk of developing anal cancer. This underscores the importance of surveillance programmes and timely interventions to prevent late diagnoses and poor outcomes. Currently, there is no established formal anal screening programme. In this review, we provide an overview of the current state of the art in managing PFCD, including novel medical, endoscopic and surgical approaches. The discussion also focuses on the relevance of establishing an anal cancer screening programme in CD, intending to propose a risk-based surveillance algorithm. The validation of this surveillance programme would be a significant step forward in improving patient care and outcomes.

UNASSIGNED: This study aimed to assess the association of body mass index (BMI) with anal high-risk human papillomavirus (HR-HPV) and biopsy-confirmed histologic anal high-grade squamous intraepithelial lesions (HSIL) among a clinic-based sample of Hispanics in Puerto Rico.
UNASSIGNED: This cross-sectional study evaluated medical records of adults who received services at the Anal Neoplasia Clinic of the University of Puerto Rico Comprehensive Cancer Center between October 2014 and December 2022. The study included 543 records with complete clinical information regarding anal HR-HPV and anal HSIL status. Chi-square and logistic regression analyses were performed.
UNASSIGNED: Mean age of participants was 44.10 ± 13.24 years, 65.2% were men, 71.7% were HIV-infected, 74.4% had anal HR-HPV infection, and 37.9% had biopsy-confirmed HSIL. Regarding BMI, 2.4% were underweight, 31.9% normal weight, and 39.0 % overweight; while 17.3 % had class I, 5.2% class II, and 4.2% class III obesity. No significant association was observed between BMI and anal HR-HPV infection in adjusted analyses. Lower odds of anal HSIL were observed among overweight individuals (OR: 0.63, 95% CI: 0.41 - 0.99) and those with class II/III obesity (OR: 0.48, 95% CI: 0.22 - 1.01) compared to adults with underweight/normal BMI, after adjusting for potential confounders. No significant association was observed for class I obesity.
UNASSIGNED: BMI was not associated with anal HR-HPV infection. Overweight and obese individuals had lower odds of having anal HSIL than adults with underweight/normal BMI. This finding could suggest underdiagnosis of HSIL among overweight/obese individuals, or reduced risk in this group.