Cancer Prevention — Diagnosis — Treatment
1. The ANCHOR Study: A Landmark in Anal Cancer Prevention
The ANCHOR trial (Anal Cancer/HSIL Outcomes Research), published in the New England Journal of Medicine in 2022 and completed in 2024, is the largest randomized controlled trial ever conducted in anal cancer prevention.
Key Findings:
- Treatment of anal high-grade squamous intraepithelial lesions (HSIL) reduced the risk of progression to anal cancer by 57–60% compared to active monitoring alone.
- The study enrolled 10,723 HIV-positive patients across 25 sites in the United States.
- High-Resolution Anoscopy (HRA) was confirmed as the essential tool for screening and treatment.
These results confirm that, as with cervical cancer, early detection and treatment of anal precancerous lesions can prevent cancer.
2. New Screening Guidelines (2024)
Based on the ANCHOR findings, two major developments have reshaped the screening landscape:
CDC Guidelines (July 2024)
The U.S. Centers for Disease Control and Prevention issued the first federal guidelines for anal cancer screening in people with HIV, with a stepwise approach tailored to different risk levels.
IANS Guidelines (2024)
The International Anal Neoplasia Society published consensus guidelines recommending screening for groups with anal cancer incidence rates more than 10-fold that of the general population.
High-Risk Groups Requiring Screening:
- HIV-positive patients — particularly MSM (men who have sex with men)
- Immunosuppressed patients (organ transplant recipients, autoimmune conditions)
- Transgender women
- Women with a history of cervical cancer or dysplasia
3. Expanding Screening Populations: Women with Cervical Cancer
New research (2025) demonstrates that women newly diagnosed with cervical cancer should also be screened for anal HPV, as:
- 48% of women with high-grade cervical epithelial lesions have concurrent anal HPV infections.
- The majority of these infections are caused by high-risk oncogenic HPV subtypes.
This significantly broadens the target population beyond the traditionally recognized high-risk groups.
4. Rising Incidence of Anal Cancer
- An estimated 10,930 new cases of anal cancer in the U.S. in 2025 (7,370 in women, 3,560 in men).
- Incidence has been steadily increasing for several decades.
- Nearly 90% of anal squamous cell carcinomas are attributed to HPV.
- The risk in HIV-positive MSM can be up to 37 times higher than the general population.
5. Therapeutic HPV Vaccines: The Next Generation
While existing vaccines (Gardasil 9) prevent new infections, they do not treat existing ones. The development of therapeutic vaccines represents one of the most promising frontiers:
DNA Vaccines
VGX-3100 is the only therapeutic HPV vaccine to have reached Phase III clinical trials (as of May 2025). It targets the E6/E7 proteins of HPV-16 and HPV-18.
Nanovaccines
In November 2025, researchers at UT Southwestern developed a nanovaccine that eradicated tumors in an animal model of late-stage metastatic HPV-related disease, opening new pathways for treatment.
Immunotherapy & Gene Therapy
- CRISPR/Cas9: Gene-editing technology that directly targets HPV oncogenes E6 and E7, disrupting carcinogenic pathways.
- Immune Checkpoint Inhibitors: Drugs that activate the immune system against HPV-positive cells.
- Combination therapeutic vaccines: Multiple immunotherapeutic approaches combined for improved efficacy.
6. The Microbiome and HPV: A New Dimension
Emerging research reveals that the composition of mucosal microbiota plays a significant role in HPV persistence or clearance:
- Certain bacterial communities promote viral clearance, while others facilitate HPV persistence.
- Researchers are developing microbiome-supporting topical treatments that could prevent new HPV infections from becoming chronic.
- Active clinical trials are studying the relationship between the anal microbiome and the risk of HPV infection or HSIL in people living with HIV.
Future Outlook: The development of topical antiviral treatments (gels) that target HPV persistence mechanisms is in clinical trials and could fundamentally change the therapeutic approach.
7. Next-Generation Prophylactic Vaccines
- Merck is developing a novel multivalent HPV vaccine with broader HPV type coverage, including types more prevalent in African and Asian populations (Phase I initiated late 2024).
- Studies are evaluating a single-dose regimen of Gardasil 9 for simplified vaccination schedules.
- The WHO reports 8 licensed HPV vaccines globally in 2025, with 5 prequalified.
- China published new HPV vaccination guidelines (2025) recommending vaccination for males aged 9–26 (gender-neutral strategy).
8. Our Clinic at the Forefront
The Anal Surgery Clinic in Athens, Greece is at the forefront of anal cancer prevention in Greece:
- Dr. Apostolos Stamatiadis is the first proctologist in Greece to systematically focus (since 2012) on anal cancer prevention through HPV detection.
- First Greek physician trained in the U.S. in cancer prevention for HIV-positive and MSM populations.
- Introduced High-Resolution Anoscopy (HRA) to Greece.
- 2,538 unique patients examined with HRA (2013–2024).
- Dr. Ioannis Gkegkes performs a large number of HRA procedures and laser treatments for HPV lesions.
- National reference center for anal HPV, receiving referrals from surgeons, gastroenterologists, dermatologists, and gynecologists.
- Genital wart treatment with laser under local anesthesia in-office.
Conclusions
The year 2025 marks a new era in the management of anal HPV. The ANCHOR study proved that treating precancerous lesions can prevent cancer. New guidelines are expanding screening populations. Therapeutic vaccines, gene therapies, and microbiome research are opening new horizons.
High-Resolution Anoscopy remains the cornerstone of secondary prevention. Specialized expertise and modern equipment are essential for its safe and effective application.
