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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 -
Abdominal Radiology (New York) Sep 2023The Society of Abdominal Radiology's Colorectal and Anal Cancer Disease-Focused Panel (DFP) first published a rectal cancer lexicon paper in 2019. Since that time, the... (Review)
Review
The Society of Abdominal Radiology's Colorectal and Anal Cancer Disease-Focused Panel (DFP) first published a rectal cancer lexicon paper in 2019. Since that time, the DFP has published revised initial staging and restaging reporting templates, and a new SAR user guide to accompany the rectal MRI synoptic report (primary staging). This lexicon update summarizes interval developments, while conforming to the original lexicon 2019 format. Emphasis is placed on primary staging, treatment response, anatomic terminology, nodal staging, and the utility of specific sequences in the MRI protocol. A discussion of primary tumor staging reviews updates on tumor morphology and its clinical significance, T1 and T3 subclassifications and their clinical implications, T4a and T4b imaging findings/definitions, terminology updates on the use of MRF over CRM, and the conundrum of the external sphincter. A parallel section on treatment response reviews the clinical significance of near-complete response and introduces the lexicon of "regrowth" versus "recurrence". A review of relevant anatomy incorporates updated definitions and expert consensus of anatomic landmarks, including the NCCN's new definition of rectal upper margin and sigmoid take-off. A detailed review of nodal staging is also included, with attention to tumor location relative to the dentate line and locoregional lymph node designation, a new suggested size threshold for lateral lymph nodes and their indications for use, and imaging criteria used to differentiate tumor deposits from lymph nodes. Finally, new treatment terminologies such as organ preservation, TNT, TAMIS and watch-and-wait management are introduced. This 2023 version aims to serve as a concise set of up-to-date recommendations for radiologists, and discusses terminology, classification systems, MRI and clinical staging, and the evolving concepts in diagnosis and treatment of rectal cancer.
Topics: Humans; Rectal Neoplasms; Anus Neoplasms; Rectum; Neoplasm Staging; Magnetic Resonance Imaging; Radiology
PubMed: 37145311
DOI: 10.1007/s00261-023-03893-2 -
The New England Journal of Medicine Jun 2022The incidence of anal cancer is substantially higher among persons living with the human immunodeficiency virus (HIV) than in the general population. Similar to cervical... (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND
The incidence of anal cancer is substantially higher among persons living with the human immunodeficiency virus (HIV) than in the general population. Similar to cervical cancer, anal cancer is preceded by high-grade squamous intraepithelial lesions (HSILs). Treatment for cervical HSIL reduces progression to cervical cancer; however, data from prospective studies of treatment for anal HSIL to prevent anal cancer are lacking.
METHODS
We conducted a phase 3 trial at 25 U.S. sites. Persons living with HIV who were 35 years of age or older and who had biopsy-proven anal HSIL were randomly assigned, in a 1:1 ratio, to receive either HSIL treatment or active monitoring without treatment. Treatment included office-based ablative procedures, ablation or excision under anesthesia, or the administration of topical fluorouracil or imiquimod. The primary outcome was progression to anal cancer in a time-to-event analysis. Participants in the treatment group were treated until HSIL was completely resolved. All the participants underwent high-resolution anoscopy at least every 6 months; biopsy was also performed for suspected ongoing HSIL in the treatment group, annually in the active-monitoring group, or any time there was concern for cancer.
RESULTS
Of 4459 participants who underwent randomization, 4446 (99.7%) were included in the analysis of the time to progression to cancer. With a median follow-up of 25.8 months, 9 cases were diagnosed in the treatment group (173 per 100,000 person-years; 95% confidence interval [CI], 90 to 332) and 21 cases in the active-monitoring group (402 per 100,000 person-years; 95% CI, 262 to 616). The rate of progression to anal cancer was lower in the treatment group than in the active-monitoring group by 57% (95% CI, 6 to 80; P = 0.03 by log-rank test).
CONCLUSIONS
Among participants with biopsy-proven anal HSIL, the risk of anal cancer was significantly lower with treatment for anal HSIL than with active monitoring. (Funded by the National Cancer Institute; ClinicalTrials.gov number, NCT02135419.).
Topics: Adult; Anus Neoplasms; Biopsy; Female; HIV Infections; Homosexuality, Male; Humans; Male; Papillomavirus Infections; Precancerous Conditions; Prospective Studies; Squamous Intraepithelial Lesions; Watchful Waiting
PubMed: 35704479
DOI: 10.1056/NEJMoa2201048 -
International Journal of Cancer Dec 2022To inform optimal approaches for detecting anal precancers, we performed a systematic review and meta-analysis of the diagnostic accuracy of anal cancer screening tests... (Meta-Analysis)
Meta-Analysis
To inform optimal approaches for detecting anal precancers, we performed a systematic review and meta-analysis of the diagnostic accuracy of anal cancer screening tests in different populations with elevated risk for anal cancer. We conducted a literature search of studies evaluating tests for anal precancer and cancer (anal intraepithelial neoplasia grade 2 or worse, AIN2+) published between January 1, 1997 to September 30, 2021 in PubMed and Embase. Titles and abstracts were screened for inclusion and included articles underwent full-text review, data abstraction and quality assessment. We estimated the prevalence of AIN2+ and calculated summary estimates and 95% confidence intervals (CI) of test positivity, sensitivity and specificity and predictive values of various testing strategies, overall and among population subgroups. A total of 39 articles were included. The prevalence of AIN2+ was 20% (95% CI, 17-29%), and ranged from 22% in men who have sex with men (MSM) living with HIV to 13% in women and 12% in MSM without HIV. The sensitivity and specificity of cytology and HPV testing were 81% and 62% and 92% and 42%, respectively, and 93% and 33%, respectively for cytology and HPV co-testing. AIN2+ risks were similar among those testing positive for cytology, HPV, or co-testing. Limited data on other biomarkers (HPV E6/E7 mRNA and p16/Ki-67 dual stain), suggested higher specificity, but lower sensitivity compared with anal cytology and HPV. Our findings provide important evidence for the development of clinical guidelines using anal cytology and HPV testing for anal cancer screening.
Topics: Anus Neoplasms; Early Detection of Cancer; Female; HIV Infections; Homosexuality, Male; Humans; Ki-67 Antigen; Male; Papillomaviridae; Papillomavirus Infections; RNA, Messenger; Sexual and Gender Minorities
PubMed: 35793241
DOI: 10.1002/ijc.34199 -
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 -
International Journal of Cancer Jan 2021Certain population groups are known to have higher than average anal cancer risk, namely persons living with HIV (PLHIV), men who have sex with men (MSM), women... (Meta-Analysis)
Meta-Analysis
Certain population groups are known to have higher than average anal cancer risk, namely persons living with HIV (PLHIV), men who have sex with men (MSM), women diagnosed with human papillomavirus (HPV)-related gynecological precancerous lesions or cancer, solid organ transplant recipients (SOTRs) and patients with autoimmune diseases. Our aim was to provide robust and comparable estimates of anal cancer burden across these groups. Summary incidence rates (IRs), as cases per 100 000 person-years (py), were calculated by fixed-effects meta-analysis. IRs were 85 (95% confidence interval [CI] = 82-89) for HIV-positive MSM (n = 7 studies; 2 229 234 py), 32 (95% CI = 30-35) for non-MSM male PLHIV (n = 5; 1626 448 py) and 22 (95% CI = 19-24) for female PLHIV (n = 6; 1 472 123 py), with strong variation by age (eg, from 16.8 < 30 years to 107.5 ≥ 60 years for HIV-positive MSM). IR was 19 (95% CI = 10-36) in HIV-negative MSM (n = 2; 48 135 py). Anal cancer IRs were much higher after diagnosis of vulvar (IR = 48 [95% CI = 38-61]; n = 4; 145 147 py) than cervical (9 [95% CI = 8-12]; n = 4; 779 098 py) or vaginal (IR = 10 [95% CI = 3-30]; n = 4; 32 671) cancer, with equivalent disparity after respective precancerous lesions. IR was 13 (95% CI = 12-15) in SOTRs (n = 5; 1 946 206 py), reaching 24.5 and 49.6 for males and females >10 years after transplant. Anal cancer IRs were 10 (95% CI = 5-19), 6 (95% CI = 3-11) and 3 (95% CI = 2-4) for systemic lupus erythematosus, ulcerative colitis and Crohn's disease, respectively. In conclusion, a unifying anal cancer risk scale, based upon comprehensive meta-analysis, can improve prioritization and standardization in anal cancer prevention/research initiatives, which are in their public health infancy.
Topics: Adult; Age Factors; Anus Neoplasms; Autoimmune Diseases; Female; Genital Neoplasms, Female; HIV Infections; Humans; Incidence; Male; Middle Aged; Organ Transplantation; Papillomavirus Infections; Precancerous Conditions; Risk Assessment; Risk Factors; Sex Factors; Sexual and Gender Minorities
PubMed: 32621759
DOI: 10.1002/ijc.33185 -
Ugeskrift For Laeger Feb 2023Anal cancer risk is increased in certain risk groups including people living with HIV (PLWH), especially in men who have sex with men, but also in organ transplant... (Review)
Review
Anal cancer risk is increased in certain risk groups including people living with HIV (PLWH), especially in men who have sex with men, but also in organ transplant recipients and women with a history of cervical or vulva dysplasia or cancer. High-resolution anoscopy (HRA) is a tool to diagnose anal high-grade squamous intraepithelial lesions (HSIL), and HRA-guided treatment of anal HSIL has been shown to reduce the risk of anal cancer in PLWH. The purpose of this review is to increase the awareness of HRA but also of tertiary prevention by digital anal rectal examination.
Topics: Male; Humans; Female; Homosexuality, Male; Sexual and Gender Minorities; Risk Factors; Endoscopy; Anus Neoplasms; Anal Canal; HIV Infections; Papillomavirus Infections
PubMed: 36896618
DOI: No ID Found -
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