RARE DISEASE
Carcinoma of the anal canal
Carcinoma of the anal canal
Carcinoma of the anal canal
Drug discovery
6
drugs
With orphan designations
Overview
Carcinoma of the anal canal is a rare malignancy, with >90% being squamous cell carcinomas linked to HPV infection [1][14]. Early symptoms include rectal bleeding, anal pain, and masses [1][17]. Diagnosis combines digital/anoscopic exams with biopsy and imaging (CT/MRI/PET) [9]. First-line treatment employs chemoradiation (Nigro protocol: 5-FU + mitomycin-C with radiation), achieving 70-90% 5-year survival for localized disease [7][15]. Salvage surgery (abdominoperineal resection) is reserved for persistent/recurrent tumors [11][13].
Therapies
Localized disease: Chemoradiation (50.4-59 Gy radiation + 5-FU/mitomycin) preserves sphincter function in 85% [3][15]
Metastatic disease: Carboplatin/paclitaxel first-line; nivolumab/pembrolizumab second-line [3][13]
Emerging: IMRT to reduce toxicity, neoadjuvant immunotherapy trials (NCT05060471) [3][13]
Categories: rare gastroenterological diseases, rare neoplastic diseases, rare transplant-related disorders
Research Papers
856 drug discovery papers about Carcinoma of the anal canal, with 2 first-in-class and 2 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
856 drug discovery papers about Carcinoma of the anal canal, with 2 first-in-class and 2 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
small molecules
2026-07-13 | Poorly Differentiated Adenocarcinoma of Anal canal Presenting as a Vulval Lump
Primary adenocarcinoma of the anal canal is a rare malignancy, accounting for fewer than 10% of anal cancers. It often presents with non-specific perianal symptoms and can be clinically mistaken for benign conditions such as a perianal abscess or Bartholin’s cyst, leading to diagnostic delay. A 69-year-old postmenopausal multipara woman presented with a three-month history of a painless, hard mass extending from the left labia majora to the left gluteal fold. She initially underwent incision and drainage for a presumed perianal abscess. Histopathological report of the excised tissue revealed poorly differentiated adenocarcinoma. Subsequent workup, including serum carcinoembryonic antigen (CEA) (2.02 ng/mL), chest x-ray, abdominal ultrasound, and CT-guided FNAC of a right lung mass, confirmed metastatic adenocarcinoma. Imaging revealed multiple pulmonary nodules in both lungs with right-sided pleural effusion, cholelithiasis, and mild endometrial collection. On immunohistochemistry (IHC), the perianal tissue sections demonstrated poorly differentiated adenocarcinoma. Our final diagnosis was carcinoma of the anal canal (Grade II, poorly differentiated adenocarcinoma) with pulmonary metastases. This case highlights that a hard, painless labio-gluteal lump in an older woman should raise suspicion for anal canal adenocarcinoma rather than benign inflammatory lesions. Early diagnosis and metastatic evaluation are essential to guide appropriate oncological management. CBMJ 2026 July: Vol. 15 No. 02 P:409-413
2026-07-07 | Knowledge gaps in tubular gut tumours: a critical appraisal of the 6th edition of the World Health Organization classification of tumours.
Gastrointestinal cancer is a global health problem. In the new 6th edition of the World Health Organization Classification of Tumours (WCT) of the Digestive System, updated evidence and guidance is provided for the aetiology, pathogenesis, diagnosis, classification, grading, staging and prognosis of these tumours. However, significant knowledge gaps remain, some of which are addressed in this review. To provide for a research framework to fill these knowledge gaps, we focused on precursor lesions and rare cancers, where the need for new evidence is most urgent. Areas with a need for further research are discussed for neoplastic precursors of the oesophagus (squamous epithelium), stomach (gastric dysplasia and adenomas), ampulla-duodenum, jejunoileum, anal canal, as well as for colorectal serrated polyposis and inflammatory bowel disease associated dysplasia (conventional and non-conventional). Knowledge gaps are also presented as they exist in rare cancers of the oesophagus (mixed type), appendix (mucinous neoplasms and mucinous adenomas), colorectum (three new subtypes) and anus, as well as for neuroendocrine tumours (grading, necrosis and two new gastric subtypes) and undifferentiated carcinomas (deficiencies of the SWI/SNF chromatin remodelling complex and mesenchymal differentiation). We identify and present research questions and persistent challenges for these entities and thus propose research frameworks that focus on specific priority areas. Progress in these core research topics for both neoplastic precursors and rare cancers will hopefully be reflected in future editions of the WCT, but many of these knowledge gaps will only be resolved with collective registries and collaborative research efforts. © 2026 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
2026-02-02 | Risk Factors for Colostomy after Chemoradiotherapy in Patients with Squamous Cell Carcinoma of the Anus: A Nationwide, Multicenter Analysis in Japan.
This study investigated the incidence of colostomy, aiming to identify its risk factors following chemoradiotherapy (CRT) for squamous cell carcinoma of the anus (SCCA) in a large Asian cohort, and to clarify the prognostic significance of a complete response (CR). While CRT is the standard of care for SCCA, the risk of colostomy remains a major concern due to its potential impact on a patient's quality of life. Prior studies focused mainly on Western populations, and data from Asian cohorts are limited. We conducted a retrospective multicenter study of 246 patients with SCCA who underwent CRT at 47 Japanese Society for Cancer of the Colon and Rectum (JSCCR)-affiliated institutions-the largest Asian cohort analyzed to date. Colostomy incidence, colostomy-free survival (CFS), and associated risk factors were assessed. Consistent with earlier Western reports, the 5-year cumulative colostomy incidence was 20.4% and the CFS rate was 65.9%. Multivariable analysis identified tumor size >50 mm (HR 9.619, P=0.0026) and male sex (HR 5.170, P<0.0001) as independent predictors of colostomy. Failure to achieve CR was strongly associated with higher colostomy risk (HR 3.732, P<0.0001), and local recurrence after CR further increased this risk (HR 16.302, P<0.0001). In this largest Asian cohort to date of patients with SCCA treated with CRT, tumor size, male sex, and abscence of CR emerged as key predictors of colostomy. Early identification of high-risk patients and achieving CR are essential for improving anal preservation and guiding individualized treatment strategies.
2026-01-27 | Mitomycin, 5-fluorouracil, and radiotherapy for anal canal cancer in a patient undergoing hemodialysis: a case report.
Anal cancer is a rare malignancy that accounts for only 0.3% of all cancer cases. Clinical data on treatment strategies for patients with special conditions, such as impaired renal function or those undergoing dialysis, are limited. Herein, we report a case highlighting the efficacy and safety of a combination regimen of mitomycin C (MMC), 5-fluorouracil (5-FU), and radiotherapy (RT) in a patient undergoing dialysis. A 65 year-old woman undergoing hemodialysis three times per week for chronic kidney disease associated with polycystic kidney disease presented with hematochezia. Biopsy confirmed human papillomavirus (HPV)-related anal squamous cell carcinoma, clinical stage cT1N0M0 (Stage I). The patient underwent two cycles of MMC and 5-FU combined with RT. The adverse events included grade 3 neutropenia, grade 3 thrombocytopenia, grade 2 nausea, grade 1 vomiting, and grade 3 diarrhea. Post-treatment endoscopic and histological evaluations confirmed a complete response. This case suggests that MMC + 5-FU + RT may be a viable treatment option with manageable toxicity, even in patients with anal canal cancer undergoing dialysis.
2026-01-21 | Anal canal adenocarcinoma due to human papillomavirus: unusual report of a case
Anal adenocarcinoma (AC) is a rare malignancy, accounting for only 5% of anal cancers, and presents significant diagnostic and therapeutic challenges due to its low incidence and limited data. The most common type of anal cancer is squamous cell carcinoma (SCC), commonly associated with human papillomavirus (HPV) infection. However, AC, particularly transitional type, has distinct clinical and biological profile. This case report discusses 66-year-old female with anal canal transitional adenocarcinoma associated with HPV, presenting with 2 cm tumor at anal verge. Diagnosis was confirmed through biopsy and imaging studies revealed no lymph node involvement. Patient underwent successful transanal resection with clear margins and post-op recovery was uneventful. Follow-up included regular clinical and imaging evaluations, with no signs of recurrence after 2 years. Treatment options for anal AC include local resection for small, well-differentiated tumors, and chemoradiotherapy for select cases. Prognostic factors such as age, tumor size and nodal involvement significantly influence survival outcomes. Continued research and case studies are necessary to refine treatment approaches and improve long-term patient care for AC.
antibodies
2026-08-05 | FDA Approval Summary: Retifanlimab for the treatment of adult patients with metastatic or inoperable locally recurrent squamous cell carcinoma of the anal canal.
On May 15, 2025, the Food and Drug Administration approved retifanlimab in combination with carboplatin and paclitaxel for treating unresectable or metastatic squamous cell carcinoma of the anal canal (SCAC), and as a single agent for second-line SCAC treatment. These approvals were based on POD1UM-303 and POD1UM-202 trials. In POD1UM-303, 308 patients with no prior systemic treatment for advanced disease were randomized 1:1 to receive retifanlimab or placebo, both combined with carboplatin and paclitaxel. The primary efficacy outcome was progression-free survival (PFS) assessed by blinded independent central review, with overall survival (OS) as a key secondary endpoint. The trial demonstrated a statistically significant PFS improvement with a hazard ratio (HR) of 0.63 (95% CI: 0.47, 0.84, p-value 0.0006). Median PFS was 9.3 months (95% CI: 7.5, 11.3) and 7.4 months (95% CI: 7.1, 7.7) in the retifanlimab and placebo arms, respectively. Interim OS results were not statistically significant (HR 0.70 [95% CI: 0.49, 1.01]), although the point estimate for OS was 29.2 months (95% CI: 24.2, NE) in the retifanlimab arm and 23 months (95% CI: 15.1, 27.9) for placebo. Second-line approval was based on POD1UM-202, a single-arm trial of 94 patients receiving single-agent retifanlimab. The independent centrally assessed overall response rate was 14% (95% CI: 8, 23). No new adverse safety signals were identified. The approval of retifanlimab as a single agent or in combination with chemotherapy provides a new therapeutic option for patients with unresectable or metastatic SCAC.
2026-08-01 | Atezolizumab, Lurbinectedin, Tarlatamab, and FOLFIRNOX in a Patient with Metastatic Small Cell Carcinoma of the Anal Canal: A Case Report and Review of the Literature
Small cell carcinoma (SCC) of the anal canal is a rare and highly aggressive neuroendocrine malignancy, and its infrequency has limited the development of evidence-based treatment approaches. As a result, management of extrapulmonary SCC (EPSCC) is often extrapolated from small cell lung cancer (SCLC), given the similar disease biology and the lack of formal approval for many SCLC-directed agents. We report the case of a 60-year-old woman who presented with metastatic SCC of the anal canal and whose disease course illustrates both the challenges and therapeutic uncertainties inherent in treating this diagnosis. Given the absence of established standards, she was treated with SCLC-based regimens and achieved a partial radiographic and clinical response to platinum-based chemotherapy in combination with the immune checkpoint inhibitor atezolizumab. Upon subsequent progression, she was treated with lurbinectedin and tarlatamab, a bispecific T-cell engager targeting delta-like ligand 3 (DLL3), reflecting evolving treatment paradigms in SCLC. Her response suggests that novel therapies developed for pulmonary small cell disease may offer benefit in select extrapulmonary cases. This case highlights the need for continued reporting of clinical experiences and prospective investigation to better define the role of emerging therapies in rare and aggressive extrapulmonary neuroendocrine malignancies.
2026-07-22 | Durable Cancer Control and Extended Long-Term Survival Following Salvage Surgery for Squamous Cell Carcinoma of the Anal Canal: A Cohort Study.
Salvage surgery is the standard-of-care for patients with squamous cell carcinoma of the anal canal (SCCa) who experience isolated locoregional failure after upfront chemoradiotherapy. While perioperative morbidity and short-term survival outcomes have been described, long-term outcomes of surgical salvage are unknown. This study examines recurrence patterns and survival in a cohort of patients with extended follow-up. A retrospective chart review was performed on a cohort of consecutive patients who underwent salvage surgery at two specialized cancer centers between 1987 and 2006. Overall, disease-specific and re-recurrence-free survival (OS, DSS, RRFS) were estimated using the Kaplan-Meier method. Prognostic variables were evaluated using univariate and multivariable Cox models. Forty patients were included (29 female, 11 male; median age 56). Median follow-up was 16.5 years (IQR 15.0-20.5) for patients alive at last follow-up. Re-recurrence developed in 52% of patients, 95% of which occurred within 3 years of salvage surgery; re-recurrence was associated with a 91% risk of subsequent SCCa-specific mortality. DSS was 45% (95% CI 30-61) at 5 years, after which point conditional 5-year DSS was 100%. Approximately half of patients who undergo salvage surgery for persistent/recurrent SCCa experience durable cancer control with extended long-term survival. Emerging treatment options such as immunotherapy should be evaluated relative to this benchmark.
2026-05-29 | Updates on Management of Anal Cancer: A New Era Has Begun.
Squamous cell carcinoma of the anal canal (SCAC) is a rare, human papillomavirus-driven malignancy with a rising global incidence and an increasingly dynamic therapeutic landscape. This review summarizes recent advances and current evidence in the management of SCAC, with a focus on immunotherapy, systemic treatment strategies, and optimization of curative-intent approaches. For locally advanced SCAC, concurrent chemoradiotherapy with fluorouracil and mitomycin C remains the standard of care, on the basis of multiple randomized trials demonstrating improved disease control and organ preservation compared with radiotherapy alone. These studies also show that treatment intensification with alternative chemotherapy, induction therapy, or radiation dose escalation does not improve outcomes. Given the curative intent, maintaining quality of life is a key consideration, and current studies are evaluating radiation dose optimization to reduce treatment-related toxicity, as well as the integration of immunotherapy to improve treatment efficacy. In metastatic SCAC, the combination of carboplatin and paclitaxel is the established first-line chemotherapy backbone. The addition of the PD-1 inhibitor retifanlimab to chemotherapy has demonstrated improved clinical outcomes and is now a preferred first-line approach. In the treatment-refractory setting, anti-PD-1 monotherapy provides modest response rates and remains a standard option for immunotherapy-naïve patients. Together, these findings summarize the current evidence base guiding the management of SCAC.
2026-05-28 | Efficacy and safety of retifanlimab across solid tumors: A systematic review and meta-analysis.
e14585 Background: Retifanlimab is a PD-1 inhibitor with demonstrated activity in several solid tumors, including FDA approved indication in squamous cell carcinoma of the anal canal (SCAC). However, its efficacy and safety across tumor types have not been systematically synthesized. Methods: We conducted a systematic review and meta analysis of prospective trials evaluating retifanlimab in solid tumors. PubMed, Embase, Cochrane Library, ClinicalTrials.gov, and oncology conferences were searched through January 2026. Pooled ORR and CR were estimated using random effects models. Subgroup analyses were performed by tumor type, treatment line, and regimen. Results: Nineteen studies encompassing 1,113 patients across phase I-III trials were included. Tumor types included SCAC, Merkel cell carcinoma (MCC), NSCLC, HNSCC, sarcoma, and MSI-H endometrial cancer. Pooled ORR was 57.2% (95% CI, 48.6–65.9%; I² = 87%); CR rate was 26.3% (95% CI, 19.7–32.8%). First-line treatment showed significantly higher ORR than later lines (79.8% vs 39.5%). By tumor type, higher ORRs were observed in HNSCC (74.8%), NSCLC (74.7%), MCC (69.4%), and SCAC (65.4%). Safety was consistent with PD-1 inhibitor class: any-grade irAEs in 27.8%, grade ≥3 in 6.3%. Conclusions: Retifanlimab demonstrates clinically meaningful antitumor activity across multiple solid tumors, with greatest benefit in first line treatment. Consistency of efficacy and safety signals supports ongoing development. Pooled ORR by tumor type. Tumor Studies Patients ORR (95% CI) SCAC 3 402 65.4% (40.7–90.2%) MCC 2 111 69.4% (37.2–101.6%) NSCLC 2 58 74.7% (39.1–110.3%) HNSCC 2 50 74.8% (53.3–96.4%) Sarcoma 3 88 37.5% (21.8–53.2%)
cell therapies
2025-12-03 | Case Report: Application of combined transplantation of multiple autologous flaps in preventing empty pelvis syndrome after radical surgery for isolated sacrococcygeal recurrence of anal canal squamous
Anal canal carcinoma is a rare malignancy, accounting for less than 3% of gastrointestinal tumors. Recurrent anal canal carcinoma, which occurs in less than 1% of cases, is often accompanied by severe complications. Surgery plays a crucial role in improving patients’ quality of life and controlling systemic paraneoplastic syndromes. This article reports a case of a 52-year-old female patient with recurrent anal canal squamous cell carcinoma (pT4bN0M0, Stage IIIB) 7 months after comprehensive treatment, complicated by rectovaginal fistula (RVF) and hypercalcemia of malignancy (HCM). Following multidisciplinary team (MDT) discussions, an innovative approach combining free omental packing with gracilis myocutaneous flap was adopted for the treatment of an isolated sacrococcygeal recurrent tumor after anal canal squamous cell carcinoma surgery. A tumor mass with a maximum diameter of 12.5 cm was completely resected. Postoperative pathological examination confirmed that no cancer cells were detected in multiple biopsies of the free resection margin, achieving R0 resection. After surgery, the patient's serum calcium level and serum squamous cell carcinoma antigen (SCC) returned to normal. Meanwhile, the bilateral combined myocutaneous flaps survived completely, RVF symptoms disappeared, the patient's quality of life was significantly improved, and the survival prognosis was enhanced.
2021-05-01 | Radical surgery for anal canal neuroendocrine carcinoma with pagetoid spread: a case report
Abstract Anal canal neuroendocrine carcinoma (NEC) with pagetoid spread (PS) is a rare disease, and its treatment strategy remains unclear. The prognosis of anal canal NEC with PS is poor. Resection margin status is very important for anorectal carcinoma because it affects survival. When accompanied by PS, the defect of the resulting perineal wound following radical surgical intervention may be necessarily enlarged to ensure the appropriate margin status. This case report discusses the treatment of a patient with advanced anal canal NEC with PS, inguinal lymph node metastasis and sphincter infiltration in which total pelvic exenteration with plastic surgery was successfully performed. The plastic surgery incorporated a gracilis muscle flap that was useful for the reconstruction of the enlarged perineal defect.
2020-06-10 | Immunotherapy in Gastrointestinal Cancers
Background: Gastrointestinal malignancies have both a high incidence rate and a high mortality rate. Immuno-oncological treatment approaches are becoming increasingly established in the treatment of gastrointestinal cancers. Summary: In this review, we give an overview of the types and effects of immunotherapies. We focus on recent studies on immunotherapies with special attention to immune checkpoint inhibition in carcinomas of the esophagus and stomach, the hepato-pancreatico-biliary system, and the colorectum including the anal channel in the metastatic setting, and we show their achievements but also their limitations. In an outlook, we discuss new approaches in immunotherapy like CAR T-cell therapy and oncolytic viruses. Key Messages: Gastrointestinal cancers show overall moderate response rates to immunotherapy. Nevertheless, subgroups such as DNA mismatch repair-deficient or microsatellite-instable tumors particularly benefit from the immune checkpoint blockade. Further studies are ongoing.
2019-01-10 | Establishment and Characterization of a Novel Cell Line Derived from a Small Cell Neuroendocrine Carcinoma of the Anal Canal.
Gastroenteropancreatic neuroendocrine carcinomas (GEP-NECs) are biologically aggressive tumors, associated with a very poor survival. Due to their rarity, our knowledge on GEP-NEC biology is very limited. The aim of this study was to establish a GEP-NEC cell line model that might contribute to a better understanding of this rare malignant disease to further develop novel therapeutic approaches in preclinical studies. Small cell neuroendocrine cancer cell line NEC-DUE3 was derived from a lymph node metastasis of a neuroendocrine carcinoma (NEC) located at the anal canal. Morphological characteristics and the expression of neuroendocrine markers were comprehensively investigated. For genetic profiling, NEC-DUE3 cells were analyzed by DNA fingerprinting. Chromosomal aberrations were mapped by array comparative genomic hybridization. NEC-DUE3 cell tumorigenicity was evaluated in vivo and the sensitivity to chemotherapeutic agents was assessed in vitro. NEC-DUE3 cells were characterized by the expression of molecular markers that are commonly observed in GEP-NECs, were sensitive to treatment with cisplatin, and able to form tumors in immunodeficient mice. We established and characterized the first small cell GEP-NEC cell line that may serve as a valuable tool to create a better understanding of the biology of these rare tumors and to develop novel treatment strategies.
2018-01-31 | Tolerability of ADXS11-001 Lm -LLO Listeria-Based Immunotherapy With Mitomycin, Fluorouracil, and Radiation for Anal Cancer
To obtain safety and preliminary efficacy data of the combination of ADXS11-001, live attenuated Listeria monocytogenes bacterium, with mitomycin, 5-fluorouracil (5-FU), and intensity modulated radiation therapy in locally advanced anal cancer.Eligibility included patients with previously untreated, nonmetastatic anal cancer with a primary tumor >4 cm or node-positive disease. Patients received 2 cycles of mitomycin and 5-FU concurrent with 54.0 Gy intensity modulated radiation therapy. One intravenous dose of ADXS11-001 (1 × 109 colony-forming units) was administered before chemoradiation; 3 additional monthly doses were given after chemoradiation.Ten patients were treated, including 1 with N2 and 4 with N3 disease. Two patients had grade 3 acute toxicities after the initial dose of ADXS11-001, including chills/rigors (n = 2), back pain (n = 1), and hyponatremia (n = 1). All ADXS11-001 toxicities occurred within 24 hours of administration. There was no apparent increase in chemoradiation toxicities or myelosuppression. One patient had a grade 5 cardiopulmonary event shortly after beginning 5-FU treatment. All 9 assessable patients had complete clinical responses by sigmoidoscopy. Eight of 9 patients (89%) are progression-free at a median follow-up of 42 months.Preliminary data show that ADXS11-001 can be safely administered with standard chemoradiation for anal cancer. Further studies of listeria-based immunotherapy with radiation are warranted.
vaccines
2023-10-23 | Characteristics of anal canal squamous cell carcinoma as an HPV-associated cancer in Japan.
The definition of the anal canal was revised in the TNM classification (8th edition). The Japanese Society for Cancer of the Colon and Rectum (JSCCR) conducted a retrospective multi-institutional study to clarify the characteristics of anal canal cancer (ACC) in Japan. The diagnoses of 1781 patients treated for ACC were squamous cell carcimoma (SCC; n = 428; 24.0%), adenosquamous cell carcinoma (n = 7; 0.4%), and adenocarcinoma (n = 1260; 70.7%). Anal carcinoma is associated with human papillomavirus (HPV) infection and is risk factor for anal SCC. Among 40 cases analyzed at Takano Hospital and 47 cases analyzed at National Cancer Center Hospital, 34 cases (85.0%) and 40 cases (85.1%), respectively were infected with HPV; HPV-16 was the most common genotype (79.4% and 82.5%). In the JSCCR retrospective multi-institutional study, the prognosis analysis by stage was performed for anal SCC cases (202 cases treated by CRT and 91 cases treated by surgery). The 5-year overall survival (OS) rates by stage did not differ between the two treatment groups to a statistically significant extent. Regarding the results of cancer treatment of patients who underwent HPV infection tests, although the 5-year OS rates by stage did not differ to a statistically significant extent due to the small number of cases, HPV-positive patients had better survival. While an HPV vaccine for anal canal SCC has already been approved internationally, HPV vaccination has already been implemented in Japan as a national immunization program for young women but not for men at present. An HPV vaccination for men is urgently needed.
2017-02-21 | Vaccine-preventable anal human papillomavirus in Australian gay and bisexual men
HPV causes ~90% of anal cancer and HPV16 is the type most commonly associated with anal cancer. Gay and bisexual men (GBM) are at greatly increased risk. We investigated patterns of vaccine-preventable anal HPV in older GBM.The Study of the Prevention of Anal Cancer (SPANC) is an ongoing, prospective cohort study of HIV-positive and HIV-negative Australian GBM. Participants completed questionnaires and underwent an anal swab for HPV genotyping using Roche Linear Array. We analysed baseline data from SPANC by HPV type, mean number of types, stratified by age and HIV status.Anal HPV results from 606 (98.2%) of 617 participants (median age 49 years, 35.7% HIV-positive) showed 525 (86.7%) had ≥1 HPV type and 178 (29.4%) had HPV16. Over one third of participants (214, 35.3%) had no nonavalent vaccine-preventable types detected. Two (0.3%) participants had all quadrivalent types and none had all nonavalent vaccine types. HIV-positive participants (p<0.001) and younger participants (p=0.059) were more likely to have more vaccine-preventable HPV types detected.Anal HPV was highly prevalent in this largely community-based GBM cohort. Vaccine-preventable HPV16 was detected in approximately one third of participants. These findings suggest that the potential efficacy of HPV vaccination of older GBM should be explored.
2009-02-23 | Carcinoma of the anal canal
There are around 5,000 new cases of anal canal cancer each year in the United States. It is of particular risk in HIV-positive populations. Many cases are related to persistent infection with human papillomavirus (HPV). The treatment of anal cancer has progressed from abdominoperineal resection mandating permanent colostomy in the 1940s through the 1970s to modern chemoradiation with sphincter preservation in around 80% of patients, even with locally advanced disease. The evolution of the treatment paradigm of this disease is a model for the treatment of malignant disease with organ preservation. Multiple randomized trials have been conducted to guide this evolution. Technological developments in the delivery of radiotherapy and anti-cancer pharmaceuticals harbor hope for further improvements in outcomes with possible reductions in toxicity and increases in tumor control. Perhaps most inspiring is the recent development of HPV vaccines that may significantly decrease the incidence of this cancer.
other
2023-06-30 | Demonstrating a Statistically Significant Association Between Anal High-Grade Squamous Intraepithelial Lesion and Positive OncoE6 Anal Test in Men Who Have Sex With Men and Are Living With HIV.
The aim of the study is to determine whether a positive OncoE6 Anal Test result has statistically significant higher odds of being associated with high-grade squamous intraepithelial lesion (HSIL) and to calculate sensitivity and specificity of this test for predicting HSIL in adult men who have sex with men and are living with HIV (MSMLWH). Men living with HIV 18 years or older having ≥atypical squamous cells of undetermined significance-grade anal cytology results were eligible to enroll in this cross-sectional study. Anal samples were collected just before the high-resolution anoscopy procedure. OncoE6 Anal Test results were compared with histology, the reference standard. Sensitivity, specificity, and odds ratio were calculated using HSIL as the threshold. Two hundred seventy-seven consented MSMLWH were enrolled between June 2017 and January 2022. Of these, 219 (79.1%) had biopsies obtained and histology performed; 81 of 219 participants (37%) had 1 or more biopsies with HSIL results while the remaining 138 of 219 (63%) had only low-grade squamous intraepithelial lesion or were negative for dysplasia. Anal samples from 7 participants (8.6%, 7/81) with HSIL and 3 (2.2%, 3/138) with low-grade squamous intraepithelial lesion had positive OncoE6 Anal Test results. Odds of having HSIL were 4.26 times higher among participants testing positive for HPV16/HPV18 E6 oncoprotein(s) (OR = 4.26, 95% CI = 1.07-16.95, p = .04). The OncoE6 Anal Test demonstrated excellent specificity, 97.83% (93.78-99.55), but poor sensitivity, 8.64% (3.55-17.0). In this highest-risk population for anal cancer, one could combine the OncoE6 Anal Test, having excellent specificity, with the anal Pap test, having higher sensitivity. Patients found having both an abnormal anal Pap and positive OncoE6 Anal Test result could be triaged for rapid scheduling of their high-resolution anoscopy.
2023-05-15 | RNA-seq analysis identifies transcriptomic profiles associated with anal cancer recurrence among people living with HIV.
Chemoradiation therapy (CRT) is the standard of care for squamous cell carcinoma of the anus (SCCA), the most common type of anal cancer. However, approximately one fourth of patients still relapse after CRT. We used RNA-sequencing technology to characterize coding and non-coding transcripts in tumor tissues from CRT-treated SCCA patients and compare them between 9 non-recurrent and 3 recurrent cases. RNA was extracted from FFPE tissues. Library preparations for RNA-sequencing were created using SMARTer Stranded Total RNA-Seq Kit. All libraries were pooled and sequenced on a NovaSeq 6000. Function and pathway enrichment analysis was performed with Metascape and enrichment of gene ontology (GO) was performed with Gene Set Enrichment Analysis (GSEA). There were 449 differentially expressed genes (DEGs) observed (390 mRNA, 12 miRNA, 17 lincRNA and 18 snRNA) between the two groups. We identified a core of upregulated genes (IL4, CD40LG, ICAM2, HLA-I (HLA-A, HLA-C) and HLA-II (HLA-DQA1, HLA-DRB5) in the non-recurrent SCCA tissue enriching to the gene ontology term 'allograft rejection', which suggests a CD4+ T cell driven immune response. Conversely, in the recurrent tissues, keratin (KRT1, 10, 12, 20) and hedgehog signaling pathway (PTCH2) genes involved in 'Epidermis Development,', were significantly upregulated. We identified miR-4316, that inhibit tumor proliferation and migration by repressing vascular endothelial growth factors, as being upregulated in non-recurrent SCCA. On the contrary, lncRNA-SOX21-AS1, implicated in the progression of many other cancers, was also found to be more common in our recurrent compared to non-recurrent SCCA. Our study identified key host factors which may drive the recurrence of SCCA and warrants further studies to understand the mechanism and evaluate their potential use in personalized treatment.Key MessageOur study used RNA sequencing (RNA-seq) to identify pivotal factors in coding and non-coding transcripts which differentiate between patients at risk for recurrent anal cancer after treatment. There were 449 differentially expressed genes (390 mRNA, 12 miRNA, 17 lincRNA and 18 snRNA) between 9 non-recurrent and 3 recurrent squamous cell carcinoma of anus (SCCA) tissues. The enrichment of genes related to allograft rejection was observed in the non-recurrent SCCA tissues, while the enrichment of genes related to epidermis development was positively linked with recurrent SCCA tissues.
1999-12-07 | Correlation between nm23-H1 overexpression and clinicopathological variables in human anal canal carcinoma.
To improve life expectancy prognostic factors other than TNM have been investigated. It is thought that nm23 protein may play a specific biological role in suppressing tumor metastasis. The purpose of this study was to elucidate the clinical significance of nm23 expression in human anal canal carcinoma. Immunostaining using anti-nm23 monoclonal antibody was performed in 22 anal canal tumors. The results were correlated with clinicopathological variables. Six cases out of 22 (27.3%) were nm23-positive. Significant association was found between nm23-H1 expression and depth of invasion, lymph node involvement and prognosis (p<0.05). There was no significant association between nm23-H1 expression, histologic type and age of the patients. nm23-H1 expression was not seen in our cases with metastasis and this may be related to nm23 gene alterations not being detectable by the monoclonal antibody used or to the presence of a subset of tumors in which nm23 gene abnormalities had not yet occurred at the time of tumor excision or biopsy. Overexpression of nm23-H1 protein in anal canal carcinoma may have implications for its metastatic potential. nm23-H1 expression would provide a more accurate evaluation of outcome for individual patients and thus improve treatment planning.
small molecules
2026-07-13 | Poorly Differentiated Adenocarcinoma of Anal canal Presenting as a Vulval Lump
Primary adenocarcinoma of the anal canal is a rare malignancy, accounting for fewer than 10% of anal cancers. It often presents with non-specific perianal symptoms and can be clinically mistaken for benign conditions such as a perianal abscess or Bartholin’s cyst, leading to diagnostic delay. A 69-year-old postmenopausal multipara woman presented with a three-month history of a painless, hard mass extending from the left labia majora to the left gluteal fold. She initially underwent incision and drainage for a presumed perianal abscess. Histopathological report of the excised tissue revealed poorly differentiated adenocarcinoma. Subsequent workup, including serum carcinoembryonic antigen (CEA) (2.02 ng/mL), chest x-ray, abdominal ultrasound, and CT-guided FNAC of a right lung mass, confirmed metastatic adenocarcinoma. Imaging revealed multiple pulmonary nodules in both lungs with right-sided pleural effusion, cholelithiasis, and mild endometrial collection. On immunohistochemistry (IHC), the perianal tissue sections demonstrated poorly differentiated adenocarcinoma. Our final diagnosis was carcinoma of the anal canal (Grade II, poorly differentiated adenocarcinoma) with pulmonary metastases. This case highlights that a hard, painless labio-gluteal lump in an older woman should raise suspicion for anal canal adenocarcinoma rather than benign inflammatory lesions. Early diagnosis and metastatic evaluation are essential to guide appropriate oncological management. CBMJ 2026 July: Vol. 15 No. 02 P:409-413
2026-07-07 | Knowledge gaps in tubular gut tumours: a critical appraisal of the 6th edition of the World Health Organization classification of tumours.
Gastrointestinal cancer is a global health problem. In the new 6th edition of the World Health Organization Classification of Tumours (WCT) of the Digestive System, updated evidence and guidance is provided for the aetiology, pathogenesis, diagnosis, classification, grading, staging and prognosis of these tumours. However, significant knowledge gaps remain, some of which are addressed in this review. To provide for a research framework to fill these knowledge gaps, we focused on precursor lesions and rare cancers, where the need for new evidence is most urgent. Areas with a need for further research are discussed for neoplastic precursors of the oesophagus (squamous epithelium), stomach (gastric dysplasia and adenomas), ampulla-duodenum, jejunoileum, anal canal, as well as for colorectal serrated polyposis and inflammatory bowel disease associated dysplasia (conventional and non-conventional). Knowledge gaps are also presented as they exist in rare cancers of the oesophagus (mixed type), appendix (mucinous neoplasms and mucinous adenomas), colorectum (three new subtypes) and anus, as well as for neuroendocrine tumours (grading, necrosis and two new gastric subtypes) and undifferentiated carcinomas (deficiencies of the SWI/SNF chromatin remodelling complex and mesenchymal differentiation). We identify and present research questions and persistent challenges for these entities and thus propose research frameworks that focus on specific priority areas. Progress in these core research topics for both neoplastic precursors and rare cancers will hopefully be reflected in future editions of the WCT, but many of these knowledge gaps will only be resolved with collective registries and collaborative research efforts. © 2026 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
2026-02-02 | Risk Factors for Colostomy after Chemoradiotherapy in Patients with Squamous Cell Carcinoma of the Anus: A Nationwide, Multicenter Analysis in Japan.
This study investigated the incidence of colostomy, aiming to identify its risk factors following chemoradiotherapy (CRT) for squamous cell carcinoma of the anus (SCCA) in a large Asian cohort, and to clarify the prognostic significance of a complete response (CR). While CRT is the standard of care for SCCA, the risk of colostomy remains a major concern due to its potential impact on a patient's quality of life. Prior studies focused mainly on Western populations, and data from Asian cohorts are limited. We conducted a retrospective multicenter study of 246 patients with SCCA who underwent CRT at 47 Japanese Society for Cancer of the Colon and Rectum (JSCCR)-affiliated institutions-the largest Asian cohort analyzed to date. Colostomy incidence, colostomy-free survival (CFS), and associated risk factors were assessed. Consistent with earlier Western reports, the 5-year cumulative colostomy incidence was 20.4% and the CFS rate was 65.9%. Multivariable analysis identified tumor size >50 mm (HR 9.619, P=0.0026) and male sex (HR 5.170, P<0.0001) as independent predictors of colostomy. Failure to achieve CR was strongly associated with higher colostomy risk (HR 3.732, P<0.0001), and local recurrence after CR further increased this risk (HR 16.302, P<0.0001). In this largest Asian cohort to date of patients with SCCA treated with CRT, tumor size, male sex, and abscence of CR emerged as key predictors of colostomy. Early identification of high-risk patients and achieving CR are essential for improving anal preservation and guiding individualized treatment strategies.
2026-01-27 | Mitomycin, 5-fluorouracil, and radiotherapy for anal canal cancer in a patient undergoing hemodialysis: a case report.
Anal cancer is a rare malignancy that accounts for only 0.3% of all cancer cases. Clinical data on treatment strategies for patients with special conditions, such as impaired renal function or those undergoing dialysis, are limited. Herein, we report a case highlighting the efficacy and safety of a combination regimen of mitomycin C (MMC), 5-fluorouracil (5-FU), and radiotherapy (RT) in a patient undergoing dialysis. A 65 year-old woman undergoing hemodialysis three times per week for chronic kidney disease associated with polycystic kidney disease presented with hematochezia. Biopsy confirmed human papillomavirus (HPV)-related anal squamous cell carcinoma, clinical stage cT1N0M0 (Stage I). The patient underwent two cycles of MMC and 5-FU combined with RT. The adverse events included grade 3 neutropenia, grade 3 thrombocytopenia, grade 2 nausea, grade 1 vomiting, and grade 3 diarrhea. Post-treatment endoscopic and histological evaluations confirmed a complete response. This case suggests that MMC + 5-FU + RT may be a viable treatment option with manageable toxicity, even in patients with anal canal cancer undergoing dialysis.
2026-01-21 | Anal canal adenocarcinoma due to human papillomavirus: unusual report of a case
Anal adenocarcinoma (AC) is a rare malignancy, accounting for only 5% of anal cancers, and presents significant diagnostic and therapeutic challenges due to its low incidence and limited data. The most common type of anal cancer is squamous cell carcinoma (SCC), commonly associated with human papillomavirus (HPV) infection. However, AC, particularly transitional type, has distinct clinical and biological profile. This case report discusses 66-year-old female with anal canal transitional adenocarcinoma associated with HPV, presenting with 2 cm tumor at anal verge. Diagnosis was confirmed through biopsy and imaging studies revealed no lymph node involvement. Patient underwent successful transanal resection with clear margins and post-op recovery was uneventful. Follow-up included regular clinical and imaging evaluations, with no signs of recurrence after 2 years. Treatment options for anal AC include local resection for small, well-differentiated tumors, and chemoradiotherapy for select cases. Prognostic factors such as age, tumor size and nodal involvement significantly influence survival outcomes. Continued research and case studies are necessary to refine treatment approaches and improve long-term patient care for AC.
antibodies
2026-08-05 | FDA Approval Summary: Retifanlimab for the treatment of adult patients with metastatic or inoperable locally recurrent squamous cell carcinoma of the anal canal.
On May 15, 2025, the Food and Drug Administration approved retifanlimab in combination with carboplatin and paclitaxel for treating unresectable or metastatic squamous cell carcinoma of the anal canal (SCAC), and as a single agent for second-line SCAC treatment. These approvals were based on POD1UM-303 and POD1UM-202 trials. In POD1UM-303, 308 patients with no prior systemic treatment for advanced disease were randomized 1:1 to receive retifanlimab or placebo, both combined with carboplatin and paclitaxel. The primary efficacy outcome was progression-free survival (PFS) assessed by blinded independent central review, with overall survival (OS) as a key secondary endpoint. The trial demonstrated a statistically significant PFS improvement with a hazard ratio (HR) of 0.63 (95% CI: 0.47, 0.84, p-value 0.0006). Median PFS was 9.3 months (95% CI: 7.5, 11.3) and 7.4 months (95% CI: 7.1, 7.7) in the retifanlimab and placebo arms, respectively. Interim OS results were not statistically significant (HR 0.70 [95% CI: 0.49, 1.01]), although the point estimate for OS was 29.2 months (95% CI: 24.2, NE) in the retifanlimab arm and 23 months (95% CI: 15.1, 27.9) for placebo. Second-line approval was based on POD1UM-202, a single-arm trial of 94 patients receiving single-agent retifanlimab. The independent centrally assessed overall response rate was 14% (95% CI: 8, 23). No new adverse safety signals were identified. The approval of retifanlimab as a single agent or in combination with chemotherapy provides a new therapeutic option for patients with unresectable or metastatic SCAC.
2026-08-01 | Atezolizumab, Lurbinectedin, Tarlatamab, and FOLFIRNOX in a Patient with Metastatic Small Cell Carcinoma of the Anal Canal: A Case Report and Review of the Literature
Small cell carcinoma (SCC) of the anal canal is a rare and highly aggressive neuroendocrine malignancy, and its infrequency has limited the development of evidence-based treatment approaches. As a result, management of extrapulmonary SCC (EPSCC) is often extrapolated from small cell lung cancer (SCLC), given the similar disease biology and the lack of formal approval for many SCLC-directed agents. We report the case of a 60-year-old woman who presented with metastatic SCC of the anal canal and whose disease course illustrates both the challenges and therapeutic uncertainties inherent in treating this diagnosis. Given the absence of established standards, she was treated with SCLC-based regimens and achieved a partial radiographic and clinical response to platinum-based chemotherapy in combination with the immune checkpoint inhibitor atezolizumab. Upon subsequent progression, she was treated with lurbinectedin and tarlatamab, a bispecific T-cell engager targeting delta-like ligand 3 (DLL3), reflecting evolving treatment paradigms in SCLC. Her response suggests that novel therapies developed for pulmonary small cell disease may offer benefit in select extrapulmonary cases. This case highlights the need for continued reporting of clinical experiences and prospective investigation to better define the role of emerging therapies in rare and aggressive extrapulmonary neuroendocrine malignancies.
2026-07-22 | Durable Cancer Control and Extended Long-Term Survival Following Salvage Surgery for Squamous Cell Carcinoma of the Anal Canal: A Cohort Study.
Salvage surgery is the standard-of-care for patients with squamous cell carcinoma of the anal canal (SCCa) who experience isolated locoregional failure after upfront chemoradiotherapy. While perioperative morbidity and short-term survival outcomes have been described, long-term outcomes of surgical salvage are unknown. This study examines recurrence patterns and survival in a cohort of patients with extended follow-up. A retrospective chart review was performed on a cohort of consecutive patients who underwent salvage surgery at two specialized cancer centers between 1987 and 2006. Overall, disease-specific and re-recurrence-free survival (OS, DSS, RRFS) were estimated using the Kaplan-Meier method. Prognostic variables were evaluated using univariate and multivariable Cox models. Forty patients were included (29 female, 11 male; median age 56). Median follow-up was 16.5 years (IQR 15.0-20.5) for patients alive at last follow-up. Re-recurrence developed in 52% of patients, 95% of which occurred within 3 years of salvage surgery; re-recurrence was associated with a 91% risk of subsequent SCCa-specific mortality. DSS was 45% (95% CI 30-61) at 5 years, after which point conditional 5-year DSS was 100%. Approximately half of patients who undergo salvage surgery for persistent/recurrent SCCa experience durable cancer control with extended long-term survival. Emerging treatment options such as immunotherapy should be evaluated relative to this benchmark.
2026-05-29 | Updates on Management of Anal Cancer: A New Era Has Begun.
Squamous cell carcinoma of the anal canal (SCAC) is a rare, human papillomavirus-driven malignancy with a rising global incidence and an increasingly dynamic therapeutic landscape. This review summarizes recent advances and current evidence in the management of SCAC, with a focus on immunotherapy, systemic treatment strategies, and optimization of curative-intent approaches. For locally advanced SCAC, concurrent chemoradiotherapy with fluorouracil and mitomycin C remains the standard of care, on the basis of multiple randomized trials demonstrating improved disease control and organ preservation compared with radiotherapy alone. These studies also show that treatment intensification with alternative chemotherapy, induction therapy, or radiation dose escalation does not improve outcomes. Given the curative intent, maintaining quality of life is a key consideration, and current studies are evaluating radiation dose optimization to reduce treatment-related toxicity, as well as the integration of immunotherapy to improve treatment efficacy. In metastatic SCAC, the combination of carboplatin and paclitaxel is the established first-line chemotherapy backbone. The addition of the PD-1 inhibitor retifanlimab to chemotherapy has demonstrated improved clinical outcomes and is now a preferred first-line approach. In the treatment-refractory setting, anti-PD-1 monotherapy provides modest response rates and remains a standard option for immunotherapy-naïve patients. Together, these findings summarize the current evidence base guiding the management of SCAC.
2026-05-28 | Efficacy and safety of retifanlimab across solid tumors: A systematic review and meta-analysis.
e14585 Background: Retifanlimab is a PD-1 inhibitor with demonstrated activity in several solid tumors, including FDA approved indication in squamous cell carcinoma of the anal canal (SCAC). However, its efficacy and safety across tumor types have not been systematically synthesized. Methods: We conducted a systematic review and meta analysis of prospective trials evaluating retifanlimab in solid tumors. PubMed, Embase, Cochrane Library, ClinicalTrials.gov, and oncology conferences were searched through January 2026. Pooled ORR and CR were estimated using random effects models. Subgroup analyses were performed by tumor type, treatment line, and regimen. Results: Nineteen studies encompassing 1,113 patients across phase I-III trials were included. Tumor types included SCAC, Merkel cell carcinoma (MCC), NSCLC, HNSCC, sarcoma, and MSI-H endometrial cancer. Pooled ORR was 57.2% (95% CI, 48.6–65.9%; I² = 87%); CR rate was 26.3% (95% CI, 19.7–32.8%). First-line treatment showed significantly higher ORR than later lines (79.8% vs 39.5%). By tumor type, higher ORRs were observed in HNSCC (74.8%), NSCLC (74.7%), MCC (69.4%), and SCAC (65.4%). Safety was consistent with PD-1 inhibitor class: any-grade irAEs in 27.8%, grade ≥3 in 6.3%. Conclusions: Retifanlimab demonstrates clinically meaningful antitumor activity across multiple solid tumors, with greatest benefit in first line treatment. Consistency of efficacy and safety signals supports ongoing development. Pooled ORR by tumor type. Tumor Studies Patients ORR (95% CI) SCAC 3 402 65.4% (40.7–90.2%) MCC 2 111 69.4% (37.2–101.6%) NSCLC 2 58 74.7% (39.1–110.3%) HNSCC 2 50 74.8% (53.3–96.4%) Sarcoma 3 88 37.5% (21.8–53.2%)
cell therapies
2025-12-03 | Case Report: Application of combined transplantation of multiple autologous flaps in preventing empty pelvis syndrome after radical surgery for isolated sacrococcygeal recurrence of anal canal squamous
Anal canal carcinoma is a rare malignancy, accounting for less than 3% of gastrointestinal tumors. Recurrent anal canal carcinoma, which occurs in less than 1% of cases, is often accompanied by severe complications. Surgery plays a crucial role in improving patients’ quality of life and controlling systemic paraneoplastic syndromes. This article reports a case of a 52-year-old female patient with recurrent anal canal squamous cell carcinoma (pT4bN0M0, Stage IIIB) 7 months after comprehensive treatment, complicated by rectovaginal fistula (RVF) and hypercalcemia of malignancy (HCM). Following multidisciplinary team (MDT) discussions, an innovative approach combining free omental packing with gracilis myocutaneous flap was adopted for the treatment of an isolated sacrococcygeal recurrent tumor after anal canal squamous cell carcinoma surgery. A tumor mass with a maximum diameter of 12.5 cm was completely resected. Postoperative pathological examination confirmed that no cancer cells were detected in multiple biopsies of the free resection margin, achieving R0 resection. After surgery, the patient's serum calcium level and serum squamous cell carcinoma antigen (SCC) returned to normal. Meanwhile, the bilateral combined myocutaneous flaps survived completely, RVF symptoms disappeared, the patient's quality of life was significantly improved, and the survival prognosis was enhanced.
2021-05-01 | Radical surgery for anal canal neuroendocrine carcinoma with pagetoid spread: a case report
Abstract Anal canal neuroendocrine carcinoma (NEC) with pagetoid spread (PS) is a rare disease, and its treatment strategy remains unclear. The prognosis of anal canal NEC with PS is poor. Resection margin status is very important for anorectal carcinoma because it affects survival. When accompanied by PS, the defect of the resulting perineal wound following radical surgical intervention may be necessarily enlarged to ensure the appropriate margin status. This case report discusses the treatment of a patient with advanced anal canal NEC with PS, inguinal lymph node metastasis and sphincter infiltration in which total pelvic exenteration with plastic surgery was successfully performed. The plastic surgery incorporated a gracilis muscle flap that was useful for the reconstruction of the enlarged perineal defect.
2020-06-10 | Immunotherapy in Gastrointestinal Cancers
Background: Gastrointestinal malignancies have both a high incidence rate and a high mortality rate. Immuno-oncological treatment approaches are becoming increasingly established in the treatment of gastrointestinal cancers. Summary: In this review, we give an overview of the types and effects of immunotherapies. We focus on recent studies on immunotherapies with special attention to immune checkpoint inhibition in carcinomas of the esophagus and stomach, the hepato-pancreatico-biliary system, and the colorectum including the anal channel in the metastatic setting, and we show their achievements but also their limitations. In an outlook, we discuss new approaches in immunotherapy like CAR T-cell therapy and oncolytic viruses. Key Messages: Gastrointestinal cancers show overall moderate response rates to immunotherapy. Nevertheless, subgroups such as DNA mismatch repair-deficient or microsatellite-instable tumors particularly benefit from the immune checkpoint blockade. Further studies are ongoing.
2019-01-10 | Establishment and Characterization of a Novel Cell Line Derived from a Small Cell Neuroendocrine Carcinoma of the Anal Canal.
Gastroenteropancreatic neuroendocrine carcinomas (GEP-NECs) are biologically aggressive tumors, associated with a very poor survival. Due to their rarity, our knowledge on GEP-NEC biology is very limited. The aim of this study was to establish a GEP-NEC cell line model that might contribute to a better understanding of this rare malignant disease to further develop novel therapeutic approaches in preclinical studies. Small cell neuroendocrine cancer cell line NEC-DUE3 was derived from a lymph node metastasis of a neuroendocrine carcinoma (NEC) located at the anal canal. Morphological characteristics and the expression of neuroendocrine markers were comprehensively investigated. For genetic profiling, NEC-DUE3 cells were analyzed by DNA fingerprinting. Chromosomal aberrations were mapped by array comparative genomic hybridization. NEC-DUE3 cell tumorigenicity was evaluated in vivo and the sensitivity to chemotherapeutic agents was assessed in vitro. NEC-DUE3 cells were characterized by the expression of molecular markers that are commonly observed in GEP-NECs, were sensitive to treatment with cisplatin, and able to form tumors in immunodeficient mice. We established and characterized the first small cell GEP-NEC cell line that may serve as a valuable tool to create a better understanding of the biology of these rare tumors and to develop novel treatment strategies.
2018-01-31 | Tolerability of ADXS11-001 Lm -LLO Listeria-Based Immunotherapy With Mitomycin, Fluorouracil, and Radiation for Anal Cancer
To obtain safety and preliminary efficacy data of the combination of ADXS11-001, live attenuated Listeria monocytogenes bacterium, with mitomycin, 5-fluorouracil (5-FU), and intensity modulated radiation therapy in locally advanced anal cancer.Eligibility included patients with previously untreated, nonmetastatic anal cancer with a primary tumor >4 cm or node-positive disease. Patients received 2 cycles of mitomycin and 5-FU concurrent with 54.0 Gy intensity modulated radiation therapy. One intravenous dose of ADXS11-001 (1 × 109 colony-forming units) was administered before chemoradiation; 3 additional monthly doses were given after chemoradiation.Ten patients were treated, including 1 with N2 and 4 with N3 disease. Two patients had grade 3 acute toxicities after the initial dose of ADXS11-001, including chills/rigors (n = 2), back pain (n = 1), and hyponatremia (n = 1). All ADXS11-001 toxicities occurred within 24 hours of administration. There was no apparent increase in chemoradiation toxicities or myelosuppression. One patient had a grade 5 cardiopulmonary event shortly after beginning 5-FU treatment. All 9 assessable patients had complete clinical responses by sigmoidoscopy. Eight of 9 patients (89%) are progression-free at a median follow-up of 42 months.Preliminary data show that ADXS11-001 can be safely administered with standard chemoradiation for anal cancer. Further studies of listeria-based immunotherapy with radiation are warranted.
vaccines
2023-10-23 | Characteristics of anal canal squamous cell carcinoma as an HPV-associated cancer in Japan.
The definition of the anal canal was revised in the TNM classification (8th edition). The Japanese Society for Cancer of the Colon and Rectum (JSCCR) conducted a retrospective multi-institutional study to clarify the characteristics of anal canal cancer (ACC) in Japan. The diagnoses of 1781 patients treated for ACC were squamous cell carcimoma (SCC; n = 428; 24.0%), adenosquamous cell carcinoma (n = 7; 0.4%), and adenocarcinoma (n = 1260; 70.7%). Anal carcinoma is associated with human papillomavirus (HPV) infection and is risk factor for anal SCC. Among 40 cases analyzed at Takano Hospital and 47 cases analyzed at National Cancer Center Hospital, 34 cases (85.0%) and 40 cases (85.1%), respectively were infected with HPV; HPV-16 was the most common genotype (79.4% and 82.5%). In the JSCCR retrospective multi-institutional study, the prognosis analysis by stage was performed for anal SCC cases (202 cases treated by CRT and 91 cases treated by surgery). The 5-year overall survival (OS) rates by stage did not differ between the two treatment groups to a statistically significant extent. Regarding the results of cancer treatment of patients who underwent HPV infection tests, although the 5-year OS rates by stage did not differ to a statistically significant extent due to the small number of cases, HPV-positive patients had better survival. While an HPV vaccine for anal canal SCC has already been approved internationally, HPV vaccination has already been implemented in Japan as a national immunization program for young women but not for men at present. An HPV vaccination for men is urgently needed.
2017-02-21 | Vaccine-preventable anal human papillomavirus in Australian gay and bisexual men
HPV causes ~90% of anal cancer and HPV16 is the type most commonly associated with anal cancer. Gay and bisexual men (GBM) are at greatly increased risk. We investigated patterns of vaccine-preventable anal HPV in older GBM.The Study of the Prevention of Anal Cancer (SPANC) is an ongoing, prospective cohort study of HIV-positive and HIV-negative Australian GBM. Participants completed questionnaires and underwent an anal swab for HPV genotyping using Roche Linear Array. We analysed baseline data from SPANC by HPV type, mean number of types, stratified by age and HIV status.Anal HPV results from 606 (98.2%) of 617 participants (median age 49 years, 35.7% HIV-positive) showed 525 (86.7%) had ≥1 HPV type and 178 (29.4%) had HPV16. Over one third of participants (214, 35.3%) had no nonavalent vaccine-preventable types detected. Two (0.3%) participants had all quadrivalent types and none had all nonavalent vaccine types. HIV-positive participants (p<0.001) and younger participants (p=0.059) were more likely to have more vaccine-preventable HPV types detected.Anal HPV was highly prevalent in this largely community-based GBM cohort. Vaccine-preventable HPV16 was detected in approximately one third of participants. These findings suggest that the potential efficacy of HPV vaccination of older GBM should be explored.
2009-02-23 | Carcinoma of the anal canal
There are around 5,000 new cases of anal canal cancer each year in the United States. It is of particular risk in HIV-positive populations. Many cases are related to persistent infection with human papillomavirus (HPV). The treatment of anal cancer has progressed from abdominoperineal resection mandating permanent colostomy in the 1940s through the 1970s to modern chemoradiation with sphincter preservation in around 80% of patients, even with locally advanced disease. The evolution of the treatment paradigm of this disease is a model for the treatment of malignant disease with organ preservation. Multiple randomized trials have been conducted to guide this evolution. Technological developments in the delivery of radiotherapy and anti-cancer pharmaceuticals harbor hope for further improvements in outcomes with possible reductions in toxicity and increases in tumor control. Perhaps most inspiring is the recent development of HPV vaccines that may significantly decrease the incidence of this cancer.
other
2023-06-30 | Demonstrating a Statistically Significant Association Between Anal High-Grade Squamous Intraepithelial Lesion and Positive OncoE6 Anal Test in Men Who Have Sex With Men and Are Living With HIV.
The aim of the study is to determine whether a positive OncoE6 Anal Test result has statistically significant higher odds of being associated with high-grade squamous intraepithelial lesion (HSIL) and to calculate sensitivity and specificity of this test for predicting HSIL in adult men who have sex with men and are living with HIV (MSMLWH). Men living with HIV 18 years or older having ≥atypical squamous cells of undetermined significance-grade anal cytology results were eligible to enroll in this cross-sectional study. Anal samples were collected just before the high-resolution anoscopy procedure. OncoE6 Anal Test results were compared with histology, the reference standard. Sensitivity, specificity, and odds ratio were calculated using HSIL as the threshold. Two hundred seventy-seven consented MSMLWH were enrolled between June 2017 and January 2022. Of these, 219 (79.1%) had biopsies obtained and histology performed; 81 of 219 participants (37%) had 1 or more biopsies with HSIL results while the remaining 138 of 219 (63%) had only low-grade squamous intraepithelial lesion or were negative for dysplasia. Anal samples from 7 participants (8.6%, 7/81) with HSIL and 3 (2.2%, 3/138) with low-grade squamous intraepithelial lesion had positive OncoE6 Anal Test results. Odds of having HSIL were 4.26 times higher among participants testing positive for HPV16/HPV18 E6 oncoprotein(s) (OR = 4.26, 95% CI = 1.07-16.95, p = .04). The OncoE6 Anal Test demonstrated excellent specificity, 97.83% (93.78-99.55), but poor sensitivity, 8.64% (3.55-17.0). In this highest-risk population for anal cancer, one could combine the OncoE6 Anal Test, having excellent specificity, with the anal Pap test, having higher sensitivity. Patients found having both an abnormal anal Pap and positive OncoE6 Anal Test result could be triaged for rapid scheduling of their high-resolution anoscopy.
2023-05-15 | RNA-seq analysis identifies transcriptomic profiles associated with anal cancer recurrence among people living with HIV.
Chemoradiation therapy (CRT) is the standard of care for squamous cell carcinoma of the anus (SCCA), the most common type of anal cancer. However, approximately one fourth of patients still relapse after CRT. We used RNA-sequencing technology to characterize coding and non-coding transcripts in tumor tissues from CRT-treated SCCA patients and compare them between 9 non-recurrent and 3 recurrent cases. RNA was extracted from FFPE tissues. Library preparations for RNA-sequencing were created using SMARTer Stranded Total RNA-Seq Kit. All libraries were pooled and sequenced on a NovaSeq 6000. Function and pathway enrichment analysis was performed with Metascape and enrichment of gene ontology (GO) was performed with Gene Set Enrichment Analysis (GSEA). There were 449 differentially expressed genes (DEGs) observed (390 mRNA, 12 miRNA, 17 lincRNA and 18 snRNA) between the two groups. We identified a core of upregulated genes (IL4, CD40LG, ICAM2, HLA-I (HLA-A, HLA-C) and HLA-II (HLA-DQA1, HLA-DRB5) in the non-recurrent SCCA tissue enriching to the gene ontology term 'allograft rejection', which suggests a CD4+ T cell driven immune response. Conversely, in the recurrent tissues, keratin (KRT1, 10, 12, 20) and hedgehog signaling pathway (PTCH2) genes involved in 'Epidermis Development,', were significantly upregulated. We identified miR-4316, that inhibit tumor proliferation and migration by repressing vascular endothelial growth factors, as being upregulated in non-recurrent SCCA. On the contrary, lncRNA-SOX21-AS1, implicated in the progression of many other cancers, was also found to be more common in our recurrent compared to non-recurrent SCCA. Our study identified key host factors which may drive the recurrence of SCCA and warrants further studies to understand the mechanism and evaluate their potential use in personalized treatment.Key MessageOur study used RNA sequencing (RNA-seq) to identify pivotal factors in coding and non-coding transcripts which differentiate between patients at risk for recurrent anal cancer after treatment. There were 449 differentially expressed genes (390 mRNA, 12 miRNA, 17 lincRNA and 18 snRNA) between 9 non-recurrent and 3 recurrent squamous cell carcinoma of anus (SCCA) tissues. The enrichment of genes related to allograft rejection was observed in the non-recurrent SCCA tissues, while the enrichment of genes related to epidermis development was positively linked with recurrent SCCA tissues.
1999-12-07 | Correlation between nm23-H1 overexpression and clinicopathological variables in human anal canal carcinoma.
To improve life expectancy prognostic factors other than TNM have been investigated. It is thought that nm23 protein may play a specific biological role in suppressing tumor metastasis. The purpose of this study was to elucidate the clinical significance of nm23 expression in human anal canal carcinoma. Immunostaining using anti-nm23 monoclonal antibody was performed in 22 anal canal tumors. The results were correlated with clinicopathological variables. Six cases out of 22 (27.3%) were nm23-positive. Significant association was found between nm23-H1 expression and depth of invasion, lymph node involvement and prognosis (p<0.05). There was no significant association between nm23-H1 expression, histologic type and age of the patients. nm23-H1 expression was not seen in our cases with metastasis and this may be related to nm23 gene alterations not being detectable by the monoclonal antibody used or to the presence of a subset of tumors in which nm23 gene abnormalities had not yet occurred at the time of tumor excision or biopsy. Overexpression of nm23-H1 protein in anal canal carcinoma may have implications for its metastatic potential. nm23-H1 expression would provide a more accurate evaluation of outcome for individual patients and thus improve treatment planning.
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Drug Discovery Landscape
6 orphan drug designations for Carcinoma of the anal canal, including 2 approved therapies.
6 orphan drug designations for Carcinoma of the anal canal, including 2 approved therapies.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
semi-synthetic chlorin-based photosensitizer | small molecules | FDA | 2025-08-18 | — | Invion Limited |
Retifanlimab [ZYNYZ] | antibodies | EMA | 2020-10-19 | 2026-03-06 | Incyte Biosciences Distribution B.V. |
retifanlimab-dlwr [Zynyz] | antibodies | FDA | 2020-03-24 | 2025-05-15 | Incyte Corporation |
nivolumab | antibodies | FDA | 2017-08-07 | — | Bristol-Myers Squibb Company |
Axalimogene filolisbac [Raligize] | vaccines | EMA | 2016-01-11 | — | Granzer Regulatory Consulting & Services GmbH |
2-Pyrazinecarbonitrile, 5-[[5-2-(3-aminopropoxy)-6-methoxyphenyl]-1H-pyrazol-3-yl]amino] monomesylate monohydrate | small molecules | FDA | 2015-04-09 | — | Acrivon Therapeutics, Inc. |
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