Screening of Anal HPV Precancerous Lesions: A Review after Last Recommendations.

Over the last decades, the incidence of anal cancer has increased worldwide. The discovery of the HPV virus as its primary cause and the natural progression of the disease, involving precancerous lesions, have resulted in significant interest in screening for anal cancer. The use of cytology testing, high-risk HPV DNA research, high-resolution anoscopy, and their combination has been adopted with variable success in detecting anal HPV precancerous lesions. Various studies have been carried out to evaluate the sensitivity and specificity of these techniques in different populations. High-risk populations for developing anal cancer have been identified through study of incidence and prevalence. Therefore, different scientific societies and experts worldwide have provided different recommendations for screening, but a universal approach has not yet been established. The inhomogeneity of different risk groups, the variable accessibility to specifical techniques, and the lack of data regarding the cost-benefit ratio of screening are the main problems to address in order to define a consensus guideline acceptable worldwide. The purpose of this paper is to provide a comprehensive review of the literature on HPV precancerous lesions and its screening, particularly after the release of recent recommendations.

Topical Protease Inhibitor Increases Tumor-Free and Overall Survival in CD4-Depleted Mouse Model of Anal Cancer.

Patients with immunodeficiencies and older age are at an increased risk of anal cancer. Transgenic K14E6/E7 mice with established high-grade anal dysplasia were treated topically at the anus with the protease inhibitor saquinavir (SQV) in the setting of CD4+ T-cell depletion to mimic immunodeficiency. To ensure tumor development, specific groups were treated with a topical carcinogen (7,12-Dimethylbenz[a]anthracene (DMBA)). The treatment groups included the vehicle (control), DMBA only, topical SQV, and topical SQV with DMBA, as well as the same four groups with CD4 depletion. The mice were monitored weekly for tumor development. Upon reaching 20 weeks of treatment, the mice were sacrificed, and their anal tissue was harvested for histological analysis. None of the mice in the SQV or control groups developed overt anal tumors, except three mice that were CD4-depleted. The CD4-depleted mice treated with DMBA had significantly increased tumor-free survival and overall survival as well as decreased tumor-volume growth over time when treated with SQV. These data suggest that topical SQV, in the setting of CD4 depletion and high-grade anal dysplasia, can increase tumor-free and overall survival; thus, it may represent a viable topical therapy to decrease the risk of progression of anal dysplasia to anal cancer.

Factors Influencing Outcomes and Survival in Anal Cancer.

BACKGROUND: We aim to ascertain prognostic factors in the current management of anal cancer within this study. METHODS: We reviewed the management and outcomes of anal cancer cases over a seven-year period, inclusive (2016-2023). The primary objectives were to assess the demographic characteristics, clinical presentation, and outcomes of all anal cancer patients within our institution. Kaplan-Meier survival analysis was used to estimate survival differences between cohorts, with statistical significance determined using log-rank testing. Cox proportional hazards regression was utilised to identify prognostic factors. Cox regression hazard ratios were reported along with confidence intervals and p-values. RESULTS: The median follow-up time for the study was 29.8 months. Seventy-five patients with anal cancer were included in this study, with 88% (66/75) being squamous cell carcinoma (SCC) and the majority having regional disease (82.7% (62/75)). The median age at diagnosis was 63.4 years (36-94). There was a female preponderance (57.3% (43/75)). In total, 84% (63/75) underwent definitive chemoradiation (dCRT), with 7/63 (11.1%) requiring a salvage abdomino-perineal resection (APR) for residual or recurrent disease. Adverse prognostic indicators include those with T4 disease hazard ratio = 3.81, (95% CI 1.13-12.83, * p = 0.04), poorly differentiated tumour disease HR = 3.37, (95% CI 1.13-10.02, * p = 0.04), having N2 nodal status HR = 5.03, (95% CI 1.11-22.8, * p = 0.04), and having metastatic disease at diagnosis HR = 5.8, (95% CI 1.28-26.42, * p = 0.02). CONCLUSION: Presenting characteristics including stage, nodal, and differentiation status remain key prognostic indicators in those diagnosed with anal malignancy.

Anal carcinoma - exploring the epidemiology, risk factors, pathophysiology, diagnosis, and treatment.

Anal carcinoma is a relatively rare tumor that accounts for approximately 2% of gastrointestinal malignancies and less than 7% of anorectal cancers. Most anal tumors originate between the anorectal junction and the anal verge. Risk factors for the disease include human papillomavirus infection, human immunodeficiency virus, tobacco use, immunosuppression, female sex, and older age. The pathogenesis of anal carcinoma is believed to be linked to human papillomavirus-related inflammation, leading to dysplasia and progression to cancer. Squamous cell carcinoma is the most common type of anal tumor, with an annual incidence of approximately 1 to 2 per 100000 persons. Treatment regarding anal cancer has emerged over time. However, chemoradiation therapy remains the mainstay approach for early localized disease. Patients with metastatic disease are treated with systemic therapy, and salvage surgery is reserved for disease recurrence following chemoradiation. This article aims to provide background information on the epidemiology, risk factors, pathology, diagnosis, and current trends in the management of anal cancer. Future directions are briefly discussed.

Association of Neoadjuvant Immunotherapy With Postoperative Major Morbidity After Oncologic Surgery.

BACKGROUND: Despite increasing use of immunotherapy in the treatment of various cancer types, understanding of its impact on postoperative complications still is limited. This study aimed to characterize the association between neoadjuvant immunotherapy and surgical outcomes for rectal, colon, anal, esophageal, lung (non-small cell), and oral cavity cancers. METHODS: Using the National Cancer Database (NCDB), the study selected patients ages 18-90 years who underwent non-palliative oncologic surgery between 2010 and 2020. The primary outcome was major morbidity, defined as hospital length of stay within the top decile of each surgery subtype, unplanned 30-day readmission, or 30-day mortality. Multivariable logistic regressions for major morbidity were performed to assess neoadjuvant immunotherapy effects by cancer type while controlling for patient demographics, Charlson-Deyo comorbidity index, cancer staging, procedure type, surgical approach, and other treatment (e.g., chemotherapy or radiotherapy). RESULTS: Of 1,348,334 cases with any of the six cancer types, the study sample included 953,612 cases. Of these cases, 4771 (0.5 %) involved neoadjuvant immunotherapy, and 948,841 (99.5 %) did not. The pooled odds ratio was 0.98 (95% confidence interval [CI] 0.81-1.19). Neoadjuvant immunotherapy was not significantly associated with major morbidity after surgery for rectal (adjusted odds ratio [aOR], 0.83; 95% CI 0.60-1.16), colon (aOR, 1.27; 95% CI 0.87-1.85), anal (aOR, 1.90; 95 % CI 0.16-23.15), esophageal (aOR, 0.35; 95% CI 0.08-1.49), lung (non-small cell) (aOR, 1.06; 95% CI 0.65-1.73), or oral (aOR, 1.10; 95% CI 0.61-2.00) cancer. CONCLUSIONS: Neoadjuvant immunotherapy is not significantly associated with postoperative complications across several cancer types. As the largest study on neoadjuvant immunotherapy postoperative complications, this study suggests that surgery in the setting of neoadjuvant immunotherapy is safe.

Hotspots of Anal Cancer Screening in a High-risk Population: A Clinical Study on Free Provision, Best Method, Self-sampling, and Independent Risk Factors.

BACKGROUND/AIM: As of 2024, anal cancer (AC) has been steadily increasing worldwide but, due to insufficient evidence, anal cancer screening (ACS) has yet to be standardized. Furthermore, most high-risk people in the world have no help paying for it. Therefore, our primary endpoint was to assess the best screening method for these subjects through a provision that was free of charge (all costs were covered by the Italian public health service). Awareness-raising campaign, determination of risk factors, education on anal self-examination, and sampling (ASS) were secondary objectives. PATIENTS AND METHODS: Screening was on a voluntary basis. Engaging in receptive anal intercourse and having a history of cervical dysplasia were the main inclusion criteria. Level 1 ACS tools included digital ano-rectal examination, anoscopy, anal Pap, and anal human papillomavirus (HPV) DNA test (both through self- and proctologist- sampling); high-resolution anoscopy (HRA) with (HRAB) or without biopsy comprised level 2 screening. High-risk people were enrolled until the available funds were exhausted. RESULTS: Fifty high-risk people (40 men who had sex with men -MSM-, 9 women, and 1 heterosexual man) were enrolled. AC was found in one HIV-seropositive MSM, high-grade squamous intraepithelial lesion in 10 (20%) MSM, low-grade squamous intraepithelial lesion LSIL in 13 cases (12 MSM and 1 woman). The combination of HRAB and Pap smear screening achieved the highest values for sensitivity, specificity, and accuracy. ASS HPV DNA test provided excellent results comparable to clinician retrieval. Overweight and college education were identified as independent factors for the risk of and prevention of AC, respectively. CONCLUSION: A free ACS not only appears justified but also recommended to people screened for AC. Excess weight represents a further risk for this population.

Impact of Ascending HPV Infection on Colorectal Cancer Risk: Evidence from a Nationwide Study.

Colorectal cancer (CRC) is a prevalent and escalating health issue in Taiwan. This nationwide study delves into the relationship between Human Papillomavirus (HPV) infection and CRC risk, employing population datasets from 2007 to 2017. Cox regression analyses revealed a statistically significant hazard ratio (HR) of 1.73 (95% CI: 1.63-1.83) for CRC in HPV-positive patients, indicating a considerably elevated risk compared to non-infected individuals. Further, stratification by sex showed males with HPV have a higher CRC risk (HR = 1.49, 95% CI: 1.40-1.58) compared to females. Age-related analysis uncovered a progressive increase in CRC risk with advancing age (HR = 34.69 for over 80 years). The study of specific CRC subtypes showed varying risks: HR = 1.74 for the colon, HR = 1.64 for the rectum, and a notably higher HR = 4.72 for the anus. Comorbid conditions such as hypertension (HR = 1.26), diabetes mellitus (HR = 1.32), and abnormal liver function (HR = 1.18) also correlate with significantly increased CRC risks. These findings suggest that HPV is a significant risk factor for CRC, with disparities in risk based on anatomical location, demographic characteristics, and comorbidities, highlighting the need for intervention strategies and targeted prevention.

Prognostic implications of HIF-1α expression in anal squamous cell carcinoma treated with intensity-modulated radiotherapy (IMRT).

Background: Hypoxia-inducible factor-1α (HIF-1α) is a crucial transcription factor activated under hypoxic conditions, known to regulate genes associated with tumor survival, progression, and response to therapy. This study aimed to evaluate the prognostic significance of HIF-1α expression in patients with anal squamous cell carcinoma (ASCC) undergoing chemoradiation therapy. Methods: We conducted a retrospective analysis of 28 ASCC patients treated with intensity-modulated radiotherapy (IMRT) at our center from 2009 to 2022. HIF-1α expression was assessed via immunohistochemistry on formalin-fixed paraffin-embedded tissue specimens. Quantitative analysis of HIF-1α expression was performed, and its relationship with clinical outcomes, including disease-free survival (DFS), locoregional relapse-free survival (LRRFS), and overall survival (OS), was examined using Cox regression models. Furthermore, ASCC tissue specimens from 17 patients were analyzed for potential PIK3CA mutations using Sanger sequencing. Results: High HIF-1α expression was significantly associated with poorer DFS (p = 0.005), LRRFS (p = 0.012), and OS (p = 0.009). HIF1α expression was marginally significantly higher in males compared to females (p = 0.056) while there was no significant difference found based on tumor stage or p16 status. However, a positive correlation was identified between BMI and HIF-1α levels (Pearson correlation r = 0.5, p = 0.0084), suggesting a link between metabolic status and tumor hypoxia. Only one patient exhibited a PIK3CA mutation, preventing a reliable assessment of its correlation with HIF-1α expression. Conclusion: Our findings underscore the importance of HIF-1α as a potential biomarker for predicting survival outcomes in ASCC patients treated with chemoradiation. The association between higher BMI and increased HIF-1α expression may provide insights into the interplay between metabolic health and tumor biology in ASCC. Further studies with larger cohorts are needed to validate these findings and explore targeted therapies focusing on HIF-1α modulation.

Emerging trends and demographic disparities in anal cancer mortality across the United States census regions: An analysis of National Center for Health Statistics mortality data.

AIMS: Anal cancer, despite its rarity, is a matter of serious concern in the United States, with an uptrend in recent years and marked racial disparities in mortality rates. The aim of this work was to investigate anal cancer mortality trends and sex race disparities in the United States from 1999 to 2020. METHOD: This is a retrospective study using data from the CDC WONDER database (1999-2020). We investigated deaths attributed to anal cancer, identified by the ICD-10 code C21.1, and excluded individuals aged 14 years and under. The Mann-Kendall trend test was used to investigate temporal trends and a t-test was used to compare continuous variables. RESULTS: Both male and female age-adjusted mortality attributed to anal cancer increased significantly during the study period across all subgroups, including race (Black and White), US Census region (Northeast, Midwest, South and West) and age (15-64 and ≥65 years) (p < 0.001 for all comparisons). For each subgroup, women demonstrated significantly higher rates of mortality than men, except in the Black population, where Black men had higher rates than Black women (0.40 vs. 0.29, p < 0.001). Additionally, Black men had significantly higher mean mortality rates than White men (0.40 vs. 0.27, p < 0.001). The highest rates of anal cancer mortality were among geriatric individuals, especially women aged ≥65 years, at 1.18 per 100 000. CONCLUSION: The rise in anal cancer mortality and racial and sex disparities present a significant challenge for healthcare providers and policy makers. Further studies are required to devise evidence-based strategies to effectively tackle this challenge.

Video vignette: incisional perineal hernia repair-perineal approach.

A 51-year-old man with a medical history of recurrent anal carcinoma after chemoradiation underwent abdominoperineal resection in 2015. The patient presents with a bulging mass in the perineal zone, associated with pain. Physical examination and MRI during the workup reveal a large mass in the perineal region.

Carboplatin and Paclitaxel Chemoradiation for Localized Anal Cancer in Patients Not Eligible for Mitomycin and 5-Fluorouracil.

BACKGROUND: Although squamous cell carcinoma of the anus (SCCA) is a relatively uncommon malignancy in the United States, it continues to increase in incidence. Treatment for locoregional disease includes mitomycin and 5-fluorouracil with radiation. This combination is associated with significant toxicity, limiting its use in patients who are older or have certain comorbidities. Carboplatin and paclitaxel (C/P) is an accepted treatment regimen for metastatic SCCA. We aim to evaluate the efficacy and toxicity of weekly C/P given with radiation for patients unable to receive standard chemoradiation for SCCA. METHODS: From our cancer registry, adult patients who received weekly intravenous C/P concurrent with standard-dose radiation for localized SCCA were included in this study. Clinical response was determined based on the evidence of disease on imaging and/or anoscopy. Toxicities were graded according to the CTCAE v5. RESULTS: Ten patients were included; eight were female, and the median age was 75.5 years (54-87). Six had T2 disease, and four had T3 tumors. Four had node-positive disease. The majority (70%) of patients were dosed at standard C (AUC 2) and P (50 mg/m2), with a limited subset requiring dose reduction for baseline performance status. Patients completed a mean of 78.3% (40-100%) of the intended treatments. A total of 89% of the patients achieved a complete clinical response. With a median follow-up of 25.8 months (3.4-50.4 months), 67% of the patients are alive and without recurrence. Two patients have had local recurrence, and one patient had metastatic progression. The most common toxicities of any grade included leukopenia (100%), anemia (100%), radiation dermatitis (100%), diarrhea (100%), and fatigue (100%). Grade 3 or higher toxicities included neutropenic fever (20%), neutropenia (30%), and anemia (30%). CONCLUSIONS: This study demonstrates promising tolerability and efficacy for weekly C/P chemoradiation for patients with anal cancer unable to receive mitomycin and 5-fluorouracil. This regimen merits further investigation in prospective clinical trials.

Does use of anal cytology as a triage test improve the performance of high-risk human papillomavirus screening in gay and bisexual men for anal cancer prevention?

Anal high-risk human papillomavirus (HRHPV) testing-based anal cancer screening gay and bisexual men (GBM) is associated with high sensitivity, but low specificity. We report the potential role of triage use of anal cytology with HRHPV testing in detecting 12-month persistent anal high-grade squamous epithelial lesions (HSIL) in a cohort of GBM in Sydney, Australia. Participants were GBM from the Study of the Prevention of Anal Cancer (SPANC) who underwent annual anal HPV testing, cytology, and high-resolution anoscopy (HRA)-guided histology. The sensitivity and specificity of five screening algorithms based on HRHPV test results with triage use of anal cytology (atypical squamous cells of undetermined significance (ASCUS) and atypical squamous cells, cannot exclude HSIL (ASC-H) used as referral thresholds) were compared to these of HRHPV testing and anal cytology alone. A total of 475 men who had valid HRHPV, cytological, and histological results at both baseline and first annual follow-up visits were included, median age 49 years (inter-quartile range: 43-56) and 173 (36.4%) GBM with human immunodeficiency virus. Of all triage algorithms assessed, two had comparable sensitivity with HRHPV testing alone in detecting persistent anal HSIL, but ~20% higher specificity and 20% lower HRA referral rates. These two algorithms involved the immediate referral of those with HPV16 and for those with non-16 HRHPV either immediate or delayed (for 12 months) referral, depending on cytology result at baseline. Triage use of anal cytology in GBM testing positive for anal HRHPV increases specificity and reduces referral rates while maintaining high sensitivity in detection of HSIL.

Synchronous Anal Squamous Cell Carcinoma and Diffuse Large B Cell Lymphoma of Stomach: the First Report of an Odd Couple.

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.

Risk of developing high-grade squamous intraepithelial lesions or anal cancer after anal condylomata treatment in people living with HIV.

AIM: 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). CONCLUSION: 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.

Perianal disease in inflammatory bowel disease: Broadening treatment and surveillance strategies for anal cancer.

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.

The role of HR-HPV integration in the progression of premalignant lesions into different cancer types.

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.

Diffusion-weighted magnetic resonance imaging as an early prognostic marker of chemoradiotherapy response in squamous cell carcinoma of the anus: An individual patient data meta-analysis.

Background and purpose: 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. Material and methods: 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%. Results: 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. Conclusions: 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.

Self-collected versus clinician-collected anal swabs for anal cancer screening: A systematic review and meta-analysis.

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.

Safety and Immunogenicity of the Nonavalent Human Papillomavirus Vaccine in Women Living with HIV.

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.

Immunotherapy in Gastrointestinal Cancers.

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.