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Current Oncology (Toronto, Ont.) Mar 2023Anal cancer is a rare cancer that accounts for about 2% of all gastrointestinal tract malignancies. Among anal cancer, squamous cell cancer is the most common... (Review)
Review
Anal cancer is a rare cancer that accounts for about 2% of all gastrointestinal tract malignancies. Among anal cancer, squamous cell cancer is the most common malignancy. The incidence of all stages of anal squamous cell cancer has been increasing. Human papillomavirus infection and immunosuppression are major risk factors for anal cancer. The management of anal cancer has evolved over the past several decades and continues to do so. Chemoradiation therapy remains the mainstay for treatment for most patients with early-stage disease, whereas systemic therapy is the primary treatment for patients with metastatic disease. Patients with persistent disease or recurrence following chemoradiation therapy are treated with salvage surgery. Access to novel cytotoxic combinations and immunotherapy has improved the outcomes of patients with advanced disease. This review provides an overview of advances in the management of anal cancer over the past two decades. This paper reviews the epidemiology, risk factors, pathology, diagnosis, and management of localized and advanced anal squamous cell cancer, highlights current knowledge gaps in the management of anal cancer, and discusses future directions.
Topics: Humans; Antineoplastic Agents; Anus Neoplasms; Chemoradiotherapy; Carcinoma, Squamous Cell; Immunotherapy
PubMed: 36975459
DOI: 10.3390/curroncol30030246 -
Current Oncology (Toronto, Ont.) Apr 2023The incidence and mortality of squamous cell carcinoma of the anus has been gradually increasing globally over the last few decades. The evolution of different... (Review)
Review
The incidence and mortality of squamous cell carcinoma of the anus has been gradually increasing globally over the last few decades. The evolution of different modalities, including immunotherapies, has changed the treatment paradigm of metastatic anal cancers. Chemotherapy, radiation therapy, and immune-modulating therapies form the backbone of treatment of anal cancer in various stages. Most anal cancers are linked to high-risk human papilloma virus (HPV) infections. HPV oncoproteins E6 and E7 are responsible for an anti-tumor immune response triggering the recruitment of tumor-infiltrating lymphocytes. This has led to the development and utilization of immunotherapy in anal cancers. Current research in anal cancer is moving forward to discover ways to incorporate immunotherapy in the treatment sequencing in various stages of anal cancers. Immune checkpoint inhibitors alone or in combination, adoptive cell therapy, and vaccines are the areas of active investigations in anal cancer in both locally advanced and metastatic settings. Immunomodulating properties of non-immunotherapies are incorporated to enhance immune checkpoint inhibitors' effectiveness in some of the clinical trials. The aim of this review is to summarize the potential role of immunotherapy in anal squamous cell cancers and future directions.
Topics: Humans; Papillomavirus Infections; Immune Checkpoint Inhibitors; Anus Neoplasms; Immunotherapy; Lymphocytes, Tumor-Infiltrating; Carcinoma, Squamous Cell
PubMed: 37232801
DOI: 10.3390/curroncol30050343 -
Annals of Oncology : Official Journal... Sep 2021
Topics: Anus Neoplasms; Follow-Up Studies; Humans; Societies, Medical
PubMed: 34175386
DOI: 10.1016/j.annonc.2021.06.015 -
American Society of Clinical Oncology... Jan 2019Our aim is to discuss the current established management of care and associated prevention strategies of anal squamous cell carcinoma (SCCA). In general, the development... (Review)
Review
Our aim is to discuss the current established management of care and associated prevention strategies of anal squamous cell carcinoma (SCCA). In general, the development of SCCA is commonly linked to a prior history of HPV. Unfortunately, HPV vaccination continues to be underutilized in the United States versus other countries. Increased acknowledgment of the importance of HPV vaccination as an anticancer vaccine should be encouraged. The present standard of care is primary chemoradiotherapy (CRT), which results in a high level of disease control for small, early-stage SCCA. More advanced cancers still fare poorly with this treatment, and the disease relapses locoregionally in the majority of cases (30%-50% of patients), resulting in an abdominoperineal resection. Current treatment recommendations are associated with substantial morbidity; alternative radiation doses and/or novel combinations of agents with CRT are needed to improve quality of life and oncologic outcomes. Cytotoxic chemotherapy remains the standard of care for treatment-naïve patients with metastatic disease, with a possible new treatment paradigm of carboplatin/weekly paclitaxel. In addition, immune checkpoint inhibition appears to have a promising role in the setting of patients with refractory disease. Several clinical trials with immunotherapeutic and vaccine approaches for locally advanced and metastatic anal cancer are ongoing, as are HPV-agnostic umbrella trials. Whenever possible, clinical trial enrollment is always encouraged for further therapeutic development in the setting of a rare cancer, given the potentially substantial global impact for other HPV-associated malignancies.
Topics: Anus Neoplasms; Carcinoma, Squamous Cell; Combined Modality Therapy; Diagnostic Imaging; Disease Management; Disease Susceptibility; Early Detection of Cancer; Humans; Neoplasm Staging; Risk Factors; Treatment Outcome
PubMed: 31099616
DOI: 10.1200/EDBK_237433 -
Deutsches Arzteblatt International Apr 2015Anal carcinoma accounts for 2-4% of all cases of colorectal and anorectal carcinoma. Its peak incidence is from age 58 to age 64; women are affected somewhat more... (Review)
Review
BACKGROUND
Anal carcinoma accounts for 2-4% of all cases of colorectal and anorectal carcinoma. Its peak incidence is from age 58 to age 64; women are affected somewhat more commonly than men. Its incidence has risen markedly in the past three decades.
METHODS
This article is based on a selective review of the literature, including the guidelines of the National Comprehensive Cancer Network and the European Society of Medical Oncology.
RESULTS
Anal carcinoma is often an incidental finding. About 85% of newly diagnosed cases are associated with an HPV infection with strain 16, 18, or 33. Radiochemotherapy with 5-fluorouracil and mitomycin C is the treatment of choice. The 5-year survival rate is 80-90%. Primary surgery with curative intent is indicated only for well-differentiated carcinoma of the anal margin (T1, N0). 10-30% of patients now undergo radical resection. The utility of endosonography and positron emission tomography for staging is debated and needs further study.
CONCLUSION
The treatment of patients with anal carcinoma requires a specialized multidisciplinary approach in accordance with the current evidence-based guidelines. The potential role of prophylactic vaccination against oncogenic types of HPV in the prevention of anal carcinoma merits further investigation.
Topics: Anus Neoplasms; Chemoradiotherapy; Combined Modality Therapy; Diagnosis, Differential; Diagnostic Imaging; Digestive System Surgical Procedures; Evidence-Based Medicine; Humans; Neoplasm Staging; Patient Care Team; Treatment Outcome
PubMed: 25891807
DOI: 10.3238/arztebl.2015.0243 -
Strahlentherapie Und Onkologie : Organ... Aug 2023Primary radiochemotherapy (RCT) constitutes the standard of care for early- and advanced-stage anal carcinoma. This retrospective study investigates the impact of dose...
PURPOSE
Primary radiochemotherapy (RCT) constitutes the standard of care for early- and advanced-stage anal carcinoma. This retrospective study investigates the impact of dose escalation on colostomy-free survival (CFS), overall survival (OS), locoregional control (LRC), progression-free survival (PFS), and acute and late toxicities in patients with squamous cell anal cancer.
METHODS
Considered were the outcomes of 87 patients with anal cancer treated with radiation/RCT between May 2004 and January 2020 at our institution. Toxicities were evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE version 5.0).
RESULTS
The 87 patients received treatment with a median boost of 63 Gy to the primary tumor. With a median follow-up of 32 months, the 3‑year CFS, OS, LRC, and PFS were 79.5%, 71.4%, 83.9%, and 78.5%, respectively. Tumor relapse occurred in 13 patients (14.9%). Dose escalation to > 63 Gy (maximum 66.6 Gy) to the primary tumor in 38/87 patients revealed a nonsignificant trend for improved 3‑year CFS (82.4% vs. 97%, P = 0.092), a significantly improved CFS for T2/T3 tumors (72.6% vs. 100%, P = 0.008), and a significantly improved 3‑year PFS for T1/T2 tumors (76.7% vs. 100%, P = 0.035). While acute toxicities did not differ, dose escalation > 63 Gy led to a higher rate of chronic skin toxicities (43.8% vs. 69%, P = 0.042). Treatment with intensity-modulated radiotherapy (IMRT) showed a significant improvement in 3‑year OS (75.4% vs. 53.8%, P = 0.048). In multivariate analysis, significant improvements for T1/T2 tumors (CFS, OS, LRC, PFS), G1/2 tumors (PFS), and IMRT (OS) were shown. The nonsignificant trend for CFS improvement with dose escalation > 63 Gy was also apparent in multivariate analysis (P = 0.067).
CONCLUSION
Dose escalation > 63 Gy (maximum 66.6 Gy) may improve CFS and PFS for certain subgroups, with a concomitant increase in chronic skin toxicities. Modern IMRT seems to be associated with an improvement in OS.
Topics: Humans; Neoplasm Recurrence, Local; Treatment Outcome; Radiotherapy, Intensity-Modulated; Chemoradiotherapy; Carcinoma, Squamous Cell; Anus Neoplasms; Epithelial Cells; Retrospective Studies
PubMed: 36862155
DOI: 10.1007/s00066-023-02056-y -
PloS One 2021HPV infection results in changes in host gene methylation which, in turn, are thought to contribute to the neoplastic progression of HPV-associated cancers. The...
HPV infection results in changes in host gene methylation which, in turn, are thought to contribute to the neoplastic progression of HPV-associated cancers. The objective of this study was to identify joint and disease-specific genome-wide methylation changes in anal and cervical cancer as well as changes in high-grade pre-neoplastic lesions. Formalin-fixed paraffin-embedded (FFPE) anal tissues (n = 143; 99% HPV+) and fresh frozen cervical tissues (n = 28; 100% HPV+) underwent microdissection, DNA extraction, HPV genotyping, bisulfite modification, DNA restoration (FFPE) and analysis by the Illumina HumanMethylation450 Array. Differentially methylated regions (DMR; t test q<0.01, 3 consecutive significant CpG probes and mean Δβ methylation value>0.3) were compared between normal and cancer specimens in partial least squares (PLS) models and then used to classify anal or cervical intraepithelial neoplasia-3 (AIN3/CIN3). In AC, an 84-gene PLS signature (355 significant probes) differentiated normal anal mucosa (NM; n = 9) from AC (n = 121) while a 36-gene PLS signature (173 significant probes) differentiated normal cervical epithelium (n = 10) from CC (n = 9). The CC progression signature was validated using three independent publicly available datasets (n = 424 cases). The AC and CC progression PLS signatures were interchangeable in segregating normal, AIN3/CIN3 and AC and CC and were found to include 17 common overlapping hypermethylated genes. Moreover, these signatures segregated AIN3/CIN3 lesions similarly into cancer-like and normal-like categories. Distinct methylation changes occur across the genome during the progression of AC and CC with overall similar profiles and add to the evidence suggesting that HPV-driven oncogenesis may result in similar non-random methylomic events. Our findings may lead to identification of potential epigenetic drivers of HPV-associated cancers and also, of potential markers to identify higher risk pre-cancerous lesions.
Topics: Adult; Aged; Anus Neoplasms; Biomarkers, Tumor; Carcinoma, Squamous Cell; Chemoradiotherapy; Clinical Trials, Phase III as Topic; DNA Methylation; Female; Follow-Up Studies; Gene Expression Regulation, Neoplastic; Genome, Human; Humans; Male; Middle Aged; Prognosis; Randomized Controlled Trials as Topic; Survival Rate; Uterine Cervical Neoplasms; Young Adult
PubMed: 34882728
DOI: 10.1371/journal.pone.0260857 -
Cancer Medicine Jan 2022Anal squamous cell carcinoma (ASCC) is the main subtype of anal cancer and has great heterogeneity in prognosis. We aimed to construct a nomogram for predicting their...
BACKGROUND
Anal squamous cell carcinoma (ASCC) is the main subtype of anal cancer and has great heterogeneity in prognosis. We aimed to construct a nomogram for predicting their 1-, 3-, and 5-year overall survival (OS) rates.
METHODS
Patients with ASCC, enrolled between January 1, 2010 and December 31, 2017, were identified from the SEER database. They were divided into a training group and a validation group in a ratio of 7:3. Univariate and multivariate Cox analyses were used to identify the prognostic factors for OS. Then a prognostic nomogram was established and validated by Harrell consistency index (C-index), area under the curve (AUC) of the receiver operating characteristic (ROC) curves, calibration plots, and decision curve analysis (DCA).
RESULTS
We identified 761 patients in training group and 326 patients in validation group. Four prognostic factors including age, sex, AJCC stage, and radiotherapy were identified and integrated to construct a prognostic nomogram. The C-index and AUC values proved the model's effectiveness and calibration plots manifested its excellent discrimination. Furthermore, in comparison to the AJCC stage, the C-index, AUC, and DCA proved the nomogram to be of good predictive value. Finally, we constructed a risk stratification model for dividing patients into low-risk, medium-risk, and high-risk groups, and there were obvious differences in OS.
CONCLUSIONS
A prognostic nomogram was firstly established for predicting the survival probability of ASCC patients and helping clinicians improve their risk management.
Topics: Aged; Anus Neoplasms; Area Under Curve; Carcinoma, Squamous Cell; Female; Humans; Male; Middle Aged; Neoplasm Staging; Nomograms; Proportional Hazards Models; ROC Curve; SEER Program; Survival Rate
PubMed: 34850581
DOI: 10.1002/cam4.4458 -
British Journal of Cancer Mar 2020Improving outcomes for uncommon tumours such as anal cancer can be challenging. Evolution of care tends to be incremental rather than transformative and identifying the...
Improving outcomes for uncommon tumours such as anal cancer can be challenging. Evolution of care tends to be incremental rather than transformative and identifying the specific factors facilitating improvement can be difficult. Outcome from specialist units may be better than that demonstrated in trials, posing challenges for development of future trials.
Topics: Anus Neoplasms; Chemoradiotherapy; Cohort Studies; Humans
PubMed: 31932753
DOI: 10.1038/s41416-019-0690-4 -
Seminars in Nephrology Sep 2016Human papillomavirus (HPV) is a common infection in kidney transplant recipients. HPV causes cervical, anal, vulvar, vaginal, penile and head and neck cancers. Kidney... (Review)
Review
Human papillomavirus (HPV) is a common infection in kidney transplant recipients. HPV causes cervical, anal, vulvar, vaginal, penile and head and neck cancers. Kidney transplant recipients have a disproportionate burden of disease given prolonged immunosuppression. Given the long pre-invasive state of precancer lesions such as cervical intraepithelial neoplasia (CIN) and anal intraepithelial neoplasia (AIN) most HPV-cancers are preventable with screening and targeted treatment of disease. Pre-transplant vaccination of age-eligible kidney transplant recipients is otherwise ideal.
Topics: Anus Neoplasms; Carcinoma in Situ; Early Detection of Cancer; Female; Graft Rejection; Humans; Immunosuppressive Agents; Kidney Failure, Chronic; Kidney Transplantation; Male; Papanicolaou Test; Papillomaviridae; Papillomavirus Infections; Papillomavirus Vaccines; Uterine Cervical Neoplasms; Vaginal Smears; Uterine Cervical Dysplasia
PubMed: 27772624
DOI: 10.1016/j.semnephrol.2016.05.016