Anal squamous cell carcinoma (ASCC) is an under-recognized but increasingly important public health issue. As its incidence increases – particularly among men who have sex with men (MSM), transgender women, people living with HIV, solid-organ transplant recipients, and women with a history of HPV-related cancers – the importance of systematic screening becomes clear. Recent international and national guidelines published in 2024 have updated anal cancer screening strategies, bringing major progress in clarifying clinical pathways and assessing innovations such as self-collected anal swabs for anal HPV testing. This article discusses recent guideline updates, clinical evidence, major barriers to implementation, and laboratory considerations relevant to anal cancer prevention, offering insights for clinicians and microbiologists aiming to incorporate anal cancer early detection into routine care.
Understanding Anal Cancer
Most anal cancers result from persistent infection with high-risk HPV, making HPV-related anal cancer a preventable disease when effective screening is in place. The progression of these cancers typically involves a clear precursor stage called anal intraepithelial neoplasia (AIN), and high-grade dysplasia, also known as HSIL – the critical stage that anal cancer screening aims to detect. Several lifestyle and immune factors influence the risk of progression from anal HPV infection to AIN and ultimately to cancer. Worth mentioning are immunosuppression – caused by HIV, transplant medications, or autoimmune disease treatments – and a history of vulvar, cervical, or vaginal dysplasia, which increases the likelihood of developing anal HSIL. Behavioral factors, including receptive anal intercourse and smoking, also elevate risk. These various factors underscore the importance of comprehensive prevention strategies that include, among others, HPV vaccination and routine screening. That said, the biological similarities between cervical and anal cancer development are striking: this is why prevention strategies developed for the cervix – such as cytology, HPV DNA molecular testing, and colposcopy-like procedures – are now being adapted for anal HPV testing and the anal canal.
Recent Guideline Updates for Anal Cancer Screening
Risk-Based Screening Recommendations
The most impactful update came from the IANS (International Anal Neoplasia Society), whose anal cancer screening guidelines set age thresholds and target populations for screening. These recommendations state that MSM and transgender women with HIV should start screening at age 35, while other HIV-positive and HIV-negative MSM should begin at 45. Solid-organ transplant recipients should be screened about ten years after transplantation, and women with a history of vulvar HSIL or cancer should be screened within a year of diagnosis. These guidelines directly address the long-standing clinical question: “Is anal cancer screening necessary?” For high-risk groups, the answer is clearly yes.
Screening procedures
Anal cancer screening relies primarily on anal cytology and high-risk HPV DNA testing. Anal cytology, often called the anal Pap test, is structurally similar to cervical cytology but requires specialized training due to differences in sample composition. On the other hand, anal HPV testing molecular testing helps identify individuals at significant risk, especially those carrying HPV-16. When cytology or HPV results are abnormal, patients are referred for high-resolution anoscopy (HRA), the diagnostic tool used to detect and manage high-grade dysplasia. One of the most important scientific developments in terms of prevention came from the ANCHOR trial, which showed that treating anal HSIL in HIV-positive individuals reduces the progression to cancer, reinforcing the clinical value of systematic anal cancer screening. This evidence has transformed screening from a theoretical preventive approach to a proven method for cancer prevention. With this benefit now confirmed, the next challenge is to implement screening consistently.
The Emerging Role of Self-Collected Anal Swabs
Self-collection is quickly gaining popularity as a safe and effective way to increase access to anal cancer screening in many diseases, similar to its role in cervical cancer programs. A recent meta-analysis of 10 studies found that self-collected swabs perform equivalently to clinician-collected swabs for HPV detection, with sample adequacy nearly identical. Cytology adequacy was slightly lower but still acceptable for many programs, especially those using primary HPV screening. Importantly, detection rates for high-risk HPV and cytological abnormalities were similar between the two methods. Additional research indicated high agreement between clinician- and self-collected samples for both HPV DNA and cytological triage. Self-collection also boosts screening participation: studies showed significantly higher participation when patients were allowed to self-collect samples at home. These findings suggest that non-invasive anal cancer screening options, including at-home sampling, can help close the gap in care for people who experience discomfort, stigma, or logistical barriers to clinic-based exams. As adoption increases, laboratories and healthcare providers will need clear workflows for validating, receiving, and processing self-collected samples.
Barriers to Implementing Anal Cancer Screening Programs
Despite growing evidence and well-defined anal cancer screening guidelines guidelines, integration into routine practice faces substantial obstacles.
Limited Access to High-Resolution Anoscopy
One of the main limitations is the lack of trained HRA professionals. High-resolution anoscopy requires specialized equipment and expertise, limiting availability to certain infectious disease centers or colorectal clinics. Long wait times and geographic disparities reduce the effectiveness of anal cancer early detection, as patients with abnormal results may not receive timely evaluation or treatment. Even in high-income countries, many communities lack local high-resolution anoscopy services.
Lack of Laboratory Standardization
Another persistent challenge is the absence of standardized protocols for anal cytology and anal HPV testing. Factors like swab type, transport medium, resuspension volume, and contamination can affect sample quality and test accuracy. Most HPV assays are validated for cervical samples, not anal ones, requiring laboratories to perform internal anal HPV assay validation and establish standardized workflows. Without harmonization, results may vary between institutions.
Clinical Workflow and Integration Barriers
Clinicians, sexual health centers, and primary care settings already face heavy workloads. Incorporating anal cancer screening into routine care requires new scheduling systems, reminders, staff training, and culturally sensitive communication strategies. Providers may also feel uncomfortable discussing anal health, especially with heterosexual men or older adults. These communication challenges can decrease screening participation even when patients meet guideline criteria.
Patient-Level Barriers and Stigma
Stigma remains one of the most complex obstacles. Many patients feel embarrassed discussing anal health or worry about discomfort during testing. Others are unaware that anal cancer symptoms often show up late and that cancer can develop silently from high-grade dysplasia. People who have faced trauma, discrimination, or medical mistrust – including many transgender and HIV-positive patients – may be less likely to participate in screening unless they are approached with sensitivity. Addressing these concerns is critical to improving participation in anal cancer prevention programs.
Laboratory Capacity and Resource Limitations
Laboratories face their own structural limitations. Since no HPV assays are officially approved for anal samples, labs must perform internal validation studies for each new workflow. Cytology labs may lack staff trained in recognizing anal intraepithelial neoplasia (AIN). Manual processing raises workload and increases the risk of errors. These limitations impact turnaround times and can cause bottlenecks even when clinicians demand for anal cancer screening increases.
Conclusions
Anal cancer screening has entered a new era. With strong evidence, comprehensive guidelines, and increasing adoption of self-collected anal swabs for anal HPV testing, clinicians and microbiologists now have the tools to significantly reduce the burden of HPV-related anal cancer. The main challenge is now ensuring it is implemented effectively and fairly. By addressing laboratory standardization, expanding clinical capacity, normalizing discussions about anal health, and integrating innovative technologies such as anal HPV self-sampling, healthcare systems can greatly improve early detection, protecting the individuals at highest risk.
Bibliography
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- Nyitray AG, Nitkowski J, McAuliffe TL, et al. Prevent Anal Cancer Self-Swab Study Team. Home-based self-sampling vs clinician sampling for anal precancer screening: The Prevent Anal Cancer Self-Swab Study. Int J Cancer. 2023 Aug 15;153(4):843-853.
- Dyer CEF, Jin F, Roberts JM, et al. Self- versus clinician-collected swabs in anal cancer screening: A clinical trial. PLoS One. 2025 Jan 9;20(1):e0312781.
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