BACKGROUND: Hemorrhoidectomy is a common procedure used to treat symptomatic hemorrhoids. However, the necessity and cost-effectiveness of routinely conducting histopathological analysis on excised tissue samples are uncertain.
METHODS: A systematic review was conducted using MEDLINE and EMBASE up to December 2023 for studies assessing the histopathological outcomes of hemorrhoidectomy specimens. Meta-analysis was performed on articles with combinable results to determine the pooled proportions of cancer and anal intraepithelial neoplasia (AIN) using the random effects model.
RESULTS: From 2974 initial search results, 12 studies were included in the review, with 48,365 resected specimens from hemorrhoidectomy. Among these, there were 11 retrospective studies and one prospective study. A meta-analysis of 11 studies revealed that the prevalence of anal cancer was low, at 0.13% (95% CI: 0.05%-0.31%). The prevalence of anal cancer and AIN combined was 1.16% (95% CI: 0.53%-2.52%).
CONCLUSIONS: This literature review estimated the probability of malignancy detection in hemorrhoid specimens sent for histopathological evaluation. The low incidence of malignant findings implies that routine analysis of hemorrhoidectomy samples may not be cost-effective. However, existing studies have yet to establish definitive risk factors for abnormal histological diagnoses to aid in the selection of specimens for selective histopathology.

The human papillomavirus is the most common sexually transmitted infection in the world. Most HPV infections clear spontaneously within 2 years of infection; however, persistent infection can result in a wide array of diseases, ranging from genital warts to cancer. Most cases of cervical, anal, and oropharyngeal cancers are due to HPV infection, with cervical cancer being one of the leading causes of cancer death in women worldwide. Screening is available for HPV and cervical cancer, but is not available everywhere, particularly in lower-resource settings. HPV infection disproportionally affects individuals living with HIV, resulting in decreased clearance, increased development of cancer, and increased mortality. The development of the HPV vaccine has shown a drastic decrease in HPV-related diseases. The vaccine prevents cervical cancer with near 100% efficacy, if given prior to first sexual activity. Vaccination uptake remains low worldwide due to a lack of access and limited knowledge of HPV. Increasing awareness of HPV and access to vaccination are necessary to decrease cancer and HPV-related morbidity and mortality worldwide.

This systematic review investigates the potential of circulating tumour DNA (ctDNA) as a predictive biomarker in the management and prognosis of squamous cell carcinoma of the anal canal (SCCA). PubMed, EMBASE, and Cochrane Central Registry of Controlled Trials were searched until 7 January 2024. Selection criteria included research articles exploring ctDNA in the context of anal cancer treatment response, recurrence risk assessment, and consideration of salvage surgery. A total of eight studies were therefore included in the final review, examining a total of 628 patients. These studies focused on three main themes: SCCA diagnosis and staging, treatment response, and patient outcomes. Significant heterogeneity was observed in terms of patient cohort, study methodology, and ctDNA biomarkers. Four studies provided information on the sensitivity of ctDNA biomarkers in SCCA, with a range of 82-100%. Seven studies noted a correlation between pre-treatment ctDNA levels and SCCA disease burden, suggesting that ctDNA could play a role as a biomarker for the staging of SCCA. Across all seven studies with paired pre- and post-treatment ctDNA samples, a trend was seen towards decreasing ctDNA levels post-treatment, with specific identification of a \'fast elimination\' group who achieve undetectable ctDNA levels prior to the end of treatment and may be less likely to experience treatment failure. Residual ctDNA detection post-treatment was associated with poorer patient prognosis. This systematic review identifies the broad potential of ctDNA as a useful and decisive tool in the management of SCCA. Further analysis of ctDNA biomarkers that include larger patient cohorts is required in order to clearly evaluate their potential role in clinical decision-making processes.

Non-acquired immunodeficiency syndrome-defining cancers (NADCs) are malignancies in persons living with human immunodeficiency virus (PLWHIV) and are not primarily due to the host\'s immunodeficiency. There is renewed clinical interest in long-term morbidities in PLWHIV as well as malignancies that occur in this population. We herein describe a 36-year-old woman with a 2-year history of an anal wound and right breast mass. She had been diagnosed with HIV infection prior to the development of these lesions. Clinical and laboratory evaluations led to diagnoses of breast and anal cancers. Chemotherapy and antiretroviral therapy were begun, but the patient discontinued these treatments early and was lost to follow-up. NADCs will continue to be a major clinical issue as the global population ages. This presentation of two NADCs (breast and anal cancers) in a PLWHIV further highlights the burden of multiple malignancies on the depleted health of HIV-infected patients. Early identification and treatment of HIV upon patients\' presentation to cancer care sites and screening for NADCs at HIV/AIDS care sites are recommended for improved outcomes.

UNASSIGNED: To review a five-year clinical practice of radical chemoradiotherapy (CRT) for anal cancers at a cancer centre in Wales.
UNASSIGNED: A retrospective audit examined the quality of radical CRT for anal cancers treated between November 2016 and November 2021 by investigating seven critical indicators set by Radiation Therapy Oncology Group and ACT II trials, (1) 95% completion of computed tomography simulation within 14 days of consent, (2) 100% CRT delivery within 28 days of computed tomography simulation, (3) 100% CRT delivery within 28 days of consent, (4) overall treatment time of RT 38 days with > 2 days breaks <5%, (5) 75% completion of concurrent chemotherapy, (6) <2% CRT related colostomies, and (7) <2% the 30-days mortality rate.
UNASSIGNED: A total of 80 anal cancers received CRT over five years. Around 95.0% underwent computed tomography simulation within 14 days of consent. The observed slight deviation was related to the Covid pandemic in 2020. About 96.3% started CRT within 28 days of computed tomography simulation. The mean duration of CRT was 37.9 days. Radiotherapy (RT) interruptions > 2 days were about 5%, and 67.5% started CRT within 28 days of consent. About 92.5% and 76.2% completed mitomycin and capecitabine without breaks, respectively. The colostomy rate was 1.2%, and the 30-day mortality was 1.2%.
UNASSIGNED: Audit results matched with the standards in six domains. Overall treatment time of 37.9 days, colostomy rates of 1.2%, and the 30-day mortality rate of 1.2% were commendable. Overall time interval between consent and CRT delivery can be achieved by time-constrained measures.

Elevated rates of human papillomavirus (HPV)-related anal high-grade squamous intraepithelial lesions (HSIL) and anal cancer (AC) in populations like men who have sex with men (MSM) living with HIV underscore the need for effective screening. While high-resolution anoscopy-guided biopsy is the gold standard, limited provider availability poses a challenge. This has spurred interest in identifying biomarkers for improved AC prevention. Antibodies against HPV16 oncoprotein E6, known as markers for cervical and oropharyngeal cancers, are the focus of the current study. The systematic review and meta-analysis included six studies meeting inclusion criteria, assessing HPV16 E6 seroprevalence in individuals with anal HSIL or AC. A two-step meta-analysis estimated pooled odds ratios and 95% confidence intervals (CI) for HPV16 E6 seroprevalence and HSIL or AC. Pooled prevalence, sensitivity, specificity, and diagnostic odds ratios were also calculated. This meta-analysis revealed a 3.6-fold increased risk of HSIL for HPV16 E6 seropositive individuals, escalating to a 26.1-fold risk increase for AC. Pooled specificity and sensitivity indicated a high specificity (0.99; 95%CI: 0.99, 0.99) but lower sensitivity (0.19; 95%CI: 0.10, 0.34) for HPV16 E6 serostatus as an AC biomarker. In conclusion, while HPV16 E6 seroprevalence demonstrates specificity as a potential biomarker for HPV-related AC, its utility as a standalone screening tool may be limited. Instead, it could serve effectively as a confirmation test, particularly in high-risk populations, alongside other diagnostic methods. Further research is imperative to explore HPV16 E6 seroconversion dynamics and alternative screening algorithms.

BACKGROUND: Women living with HIV (WLWH) are at increased risk of human papillomavirus (HPV)-related cancers. Throughout Europe, there is great heterogeneity among guidelines for screening programmes, access to HPV testing and HPV vaccination. The aim of this systematic review is to summarize available data on screening and prevention measures for HPV-related anogenital cancers in WLWH across the WHO European Region (WER).
METHODS: The systematic review followed the PRISMA guidelines and was registered on Prospero. PubMed, Embase and Web of Science databases were searched to identify available studies, written in English and published between 2011 and 2022. A metanalysis was conducted using random-effects models to calculate pooled prevalence of HPV. Subgroup analyses were conducted according to country and HPV testing.
RESULTS: Thirty-four articles involving 10 336 WLWH met the inclusion criteria. Studies were heterogenous in their methodology and presentation of results: 73.5% of studies focused on cervical cancer prevention, and only 4.4% on anal cancer; 76.5% of studies conducted HPV testing as a routine part of screening. The prevalence of high-risk HPV was 30.5-33.9% depending on the detection method used. A total of 77% of WLWH had cervical cytology results reported. Six studies reported the positive association of CD4 cell count <200 cells/μL with HPV prevalence and cervical abnormalities. Anal HPV testing was conducted in <8% of participants. HPV vaccination was completed in 5.6% of women (106/1902) with known vaccination status. There was no information about the vaccination status of the majority of women in the analysed studies (8434/10336).
CONCLUSIONS: Data about screening of HPV-related anogenital cancer in WLWH in Europe are heterogenous and lacking, especially in relation to anal cancer. HPV DNA testing is not routinely done as part of screening for HPV-related cancer; guidelines should include indications for when to use this test. Low CD4 count is a risk factor for HPV infection and cytological abnormalities. HPV vaccination data are poor and, when available, vaccination rates are very low among WLWH in Europe. This review concludes that significant improvements are required for data and also consistency on guidelines for HPV screening, prevention and vaccination in WLWH.

The diagnosis of anal cancer is relatively uncommon, but its incidence has been steadily increasing in high-risk populations. In the 2001 Bethesda System for Reporting Cervical Cytology, anal cytology was introduced as a component. Since then, it has been recognized as a potential tool for screening anal cancer, often in conjunction with high-resolution anoscopy. There are notable similarities between anal cancer and cervical cancer, including the causative role of human papillomavirus. However, there are also significant differences, particularly in terms of disease prevalence. Anal cytology may be used as a primary screening test, and in the event of abnormalities, patients are subsequently directed for high-resolution anoscopy. However, the best approach for anal cancer screening is yet to be determined and uniformly implemented. This comprehensive review article provides an in-depth analysis of the epidemiology and incidence of anal precursor and malignant lesions. It explores the various methods of sample procurement, preparation, interpretation (including sensitivity and specificity), and reporting terminology in anal cytology. The article also addresses the significance of concurrent high-risk human papillomavirus screening in anal cytology and its role in screening programs. Furthermore, it discusses the follow-up, prevention, and subsequent management strategies for anal cancers. By synthesizing current knowledge in these areas, this review aims to provide a comprehensive understanding of anal cytology and its implications in the early detection, prevention, and management of anal neoplasia and cancer.

BACKGROUND: Squamous cell carcinoma of the anus (SCCA) is a rare tumor. While most patients with locally advanced disease are cured with chemo-radiotherapy, about a quarter eventually experience metastatic recurrence. Standard treatment for advanced disease is chemotherapy, but recently evidence on the activity of immunotherapy has been reported. We performed a systematic review and meta-analysis of prospective trials testing immune-checkpoint inhibitors (ICIs) in patients with SCCA.
OBJECTIVE: We aimed to evaluate the overall response rate (ORR) and the disease control rate (DCR) of ICIs in patients with advanced SCCA.
METHODS: We systematically searched PubMed, Embase, and Scopus, through December 31, 2022, for prospective trials assessing ICIs in patients with advanced SCCA. The primary and secondary endpoints were respectively ORR and DCR.
RESULTS: Six prospective trials were included in the analysis, one of which was randomized. Overall, seven treatment arms and 347 patients have been analyzed. Five treatment arms tested ICIs as monotherapy and two arms examined ICIs in combination with cetuximab and bevacizumab, respectively. The pooled ORR was 13% (95%CI, 10%-17%), with a DCR of 57% (95%CI, 40%-74%). Results did not change in a sensitivity analysis, which excluded the two treatment arms testing the combination of ICIs with other drugs.
CONCLUSIONS: The efficacy of ICIs in SCCAs is low. Combination strategies with targeted drugs or chemotherapy might represent a better therapeutic strategy for these patients. Further studies are awaited to identify resistance mechanisms to ICIs and optimize their efficacy.

BACKGROUND: (Chemo)radiation may be a required treatment in young women with pelvic malignancies. Irradiation may result in ovarian and uterine failure, compromising the fertility of those patients. While ovarian transposition is an established method to move the ovaries away from the irradiation field, similar surgical procedures regarding the uterus remain investigational. The aim of this study was to carry out a systematic review of the literature on uterine displacement techniques (ventrofixation/transposition) and to simulate the radiation dose received by the uterus in different heights place after the procedures.
METHODS: The systematic review was performed according PRISMA guidelines. PubMed, Scopus, Web of Science and EMBASE were queried to identify included study until March 2023. Retrospectively, a dosimetric study was also performed and Volumetric Modulated Arc Therapy (VMAT) radiotherapy treatment plans were calculated, to assess the dose received by the uterus according to hypothetical different displacement positions taking the case of irradiation for rectal or anal cancer as model.
RESULTS: A total of 187 studies were included, after the screening 9 studies were selected for synthesis. Data from the dose simulation revealed that the transposition approach was the most protective with a maximum dose of about 3 and 8 Gy for anal and rectal cancer respectively. None of the simulated ventrofixation positions received a Dmean surpassing 14 Gy.
CONCLUSIONS: According to the literature review and the simulation results of the present study we may conclude are feasible and safe as fertility sparing approach in young rectal/anal cancer patients.