A quiet revolution in cancer prevention is underway, transforming care for people living with HIV.
When Daniel Garza was diagnosed with anal cancer a decade ago, he had never heard of the disease. "Do you mean colorectal cancer?" he asked his doctor.
At the time, Garza had been living with HIV for 14 years but didn't know that gay and bisexual men, especially those with HIV, face significantly elevated anal cancer risk 3 . His experience reflects a common knowledge gap—both among patients and healthcare providers—about this preventable disease.
The landscape of anal cancer prevention has dramatically changed since Garza's diagnosis. Groundbreaking research has not only demonstrated that screening and treatment can prevent anal cancer but has also revealed that these interventions make sound economic sense. For people living with HIV, particularly men who have sex with men (MSM) and women with specific risk factors, these advances offer new hope against a cancer whose incidence has been rising steadily 4 5 .
Although anal cancer remains rare in the general population, its incidence has been increasing across multiple demographic groups 4 . The burden falls disproportionately on specific populations: people living with HIV have a risk of developing anal cancer that is significantly higher than the general population 4 .
per 100,000 person-years
MSM with HIV face the highest riskper 100,000 person-years
Women with HIV incidence rateper 100,000 person-years
HIV-negative MSM intermediate riskNearly all anal cancers are caused by persistent infection with high-risk strains of human papillomavirus (HPV), particularly HPV16 3 5 . Like cervical cancer, anal cancer develops slowly, beginning with precancerous growths called high-grade squamous intraepithelial lesions (HSIL) that can progress to cancer if left untreated 5 .
The Anal Cancer HSIL Outcomes Research (ANCHOR) study, published in 2022, marked a turning point in anal cancer prevention. This large, NCI-sponsored randomized clinical trial demonstrated for the first time that detecting and treating precancerous anal growths could substantially reduce the risk of developing anal cancer in people with HIV 3 .
The ANCHOR trial enrolled people with HIV aged 35 years and older with confirmed high-grade squamous intraepithelial lesions (HSIL). Participants were randomly assigned to one of two groups:
Received regular check-ups but no immediate treatment for HSIL
Received procedures to remove or destroy precancerous lesions
Treating anal HSIL reduced the risk of progressing to anal cancer by 57% compared to active monitoring alone 7 .
| Metric | Active Monitoring Group | Treatment Group | Significance |
|---|---|---|---|
| Progression to anal cancer | 1.8% over 48 months | Significantly lower | 57% reduction in risk 7 |
| Primary outcome | Higher cancer incidence | Lower cancer incidence | First proof that treating HSIL prevents cancer 6 |
| Impact on guidelines | - | - | Informed first federal screening recommendations 6 |
Anal cancer screening employs a multi-step approach that adapts techniques proven successful in cervical cancer prevention:
Often called "anal Pap smear," this test collects cells from the anal canal using a swab. The cells are examined under a microscope for abnormalities 2 5 .
Analyzes the cell sample for the presence of high-risk HPV strains, particularly HPV16 and HPV18, which cause most anal cancers 1 5 .
A physical examination where clinicians feel for abnormalities in the anal canal 2 .
This specialized procedure uses a magnifying instrument to closely examine the anal canal. If abnormal areas are found, the physician can perform biopsies for definitive diagnosis 2 4 . HRA is considered the gold standard for diagnosing precancerous anal lesions but requires specialized training and equipment 3 .
| Method | Purpose | Key Advantages | Limitations |
|---|---|---|---|
| Anal Cytology | Initial screening | Simple, minimally invasive | Less reliable than HPV testing 2 |
| HPV Testing | Initial screening | Identifies high-risk strains | May cause unnecessary follow-up without genotyping 1 |
| DARE | Physical examination | Detects palpable cancers | Limited sensitivity for precancer 2 |
| HRA | Diagnosis | Gold standard, allows biopsy | Limited availability, requires expertise 3 |
With the clinical benefits established, health economists and researchers turned to a critical question: Is anal cancer screening a prudent use of limited healthcare resources? The answer, according to recent sophisticated analyses, is a qualified yes.
A 2025 cost-effectiveness study published in the Annals of Internal Medicine used microsimulation modeling to evaluate various screening approaches for MSM with HIV 1 . The research examined multiple variables:
35, 40, or 45 years
Annual, every 2, 3, or 4 years
Cytology, HPV testing, combinations
The findings revealed that initiating screening at age 35 outperformed later start ages, with incremental cost-effectiveness ratios (ICERs) ranging from $87,731 for quadrennial (every 4 years) screening to $350,100 for annual screening 1 8 .
The most efficient screening strategies shared common features:
Screening every 2-4 years provided better value than annual screening
Tests specifically targeting HPV16 and HPV18 demonstrated particular cost-effectiveness
Using HPV testing to determine who needs more intensive follow-up conserved resources while maintaining effectiveness 1
| Screening Strategy | Screening Interval | Incremental Cost-Effectiveness Ratio (ICER) | Key Features |
|---|---|---|---|
| HPV16 Testing | Every 4 years | $81,341/QALY | Highly specific for primary carcinogen 1 |
| HPV16/18 Testing | Every 2-3 years | $81,341-$Undisclosed/QALY | Targets two most risky HPV types 1 |
| High-risk HPV | Every 2-3 years | Moderate range | Broad detection of multiple risky types 1 |
| Cytology with HPV Triage | Annual | Higher range ($223,895/QALY for annual) | Traditional method, more frequent 1 8 |
QALY = Quality-Adjusted Life Year, a standard health economic measure that combines both quantity and quality of life. Lower ICER values indicate better cost-effectiveness.
Advancements in anal cancer screening depend on specialized reagents and materials that enable precise detection and diagnosis. Here are key components of the research toolkit:
Detection kits that identify the presence of high-risk HPV DNA in anal cell samples, serving as the frontline screening tool 5 .
Specific primers and probes that distinguish between HPV16, HPV18, and other high-risk types, allowing for risk stratification 1 .
Chemical stains like Papanicolaou stain that enable microscopic examination of anal cells for abnormalities 5 .
Immunocytochemistry reagents that detect simultaneous expression of p16 and Ki-67 proteins, improving identification of transforming HPV infections 5 .
Materials for tissue processing, embedding, sectioning, and staining of biopsy specimens, including hematoxylin and eosin (H&E) stains 5 .
Antibodies and detection systems that highlight p16 overexpression as a marker of HPV-induced cellular transformation in biopsy tissue 5 .
Including swabs and transport media designed specifically for collecting and preserving anal cell samples 3 .
High-resolution anoscopes, acetic acid for acetowhitening, and lugol's solution for staining during high-resolution anoscopy procedures 4 .
Research continues to refine screening strategies and overcome barriers:
Studies show that 89% of participants returned self-swab kits for anal cancer screening, compared to only 74% compliance with clinic-based screening 3 . This approach could reduce disparities by reaching people who face barriers to clinic visits.
Investigators are exploring DNA methylation and HPV E6/E7 mRNA testing as potentially more accurate screening tools 5 .
Although initially developed for cervical cancer prevention, Gardasil has been approved for anal cancer prevention and may reduce future incidence 3 .
Despite exciting progress, significant hurdles remain:
There's a critical shortage of providers trained in high-resolution anoscopy, creating diagnostic bottlenecks 3 .
Translating recommendations into routine clinical practice requires education and systemic changes 2 .
Lower screening rates have been documented among people of color, representing concerning health inequities 4 .
The evidence is now clear: anal cancer screening for high-risk individuals, particularly people living with HIV, represents that rare combination of clinical benefit and economic wisdom.
As Daniel Garza, now an advocate for cancer prevention, reflects: "I believe that my story has a purpose. If my story can help someone else get the health care they need and get their lives back on track, then I want to share it" 3 .
The journey from unknown risk to preventable disease has been long, but the path forward is clear. With cost-effective screening strategies, emerging technologies like self-collection kits, and updated guidelines, we stand at the threshold of making anal cancer increasingly rare among those at highest risk. The challenge now lies in implementing these advances equitably and efficiently, ensuring that all who can benefit have access to these life-saving interventions.