What is the recommended frequency for anal PAP (Papanicolaou) testing in an adult patient with no significant medical history but at high risk for anal cancer due to factors such as Human Papillomavirus (HPV) or Human Immunodeficiency Virus (HIV) infection, or high-risk sexual behaviors?

Anal PAP Testing Frequency in High-Risk Populations

Routine anal cytology screening is not officially recommended by the CDC 2021 STI Treatment Guidelines due to insufficient evidence, though some specialized centers perform annual screening in high-risk populations (persons with HIV, MSM, those with receptive anal intercourse) when high-resolution anoscopy referral is available. 1

Current Evidence-Based Recommendations

Official Guideline Position

The CDC explicitly states that data are insufficient to recommend routine anal cancer screening with anal cytology in persons with HIV infection, MSM without HIV infection, and the general population. 1 This represents the most authoritative current guidance despite the elevated cancer risk in these populations.

What IS Recommended: Digital Anorectal Examination (DARE)

• Annual DARE should be performed to detect palpable masses in persons with HIV infection and MSM without HIV with a history of receptive anal intercourse. 1, 2
• DARE is acceptable to patients and has low risk for adverse outcomes. 1, 3
• This examination can detect early anal cancer but has limitations in identifying pre-cancerous lesions. 1

Practice Patterns at Specialized Centers

When Cytology Screening Is Performed

Some clinical centers do implement anal cytology screening programs despite lack of official recommendation, but only when referral pathways to high-resolution anoscopy (HRA) and biopsy are available. 1 Without HRA access, cytology screening should not be initiated. 2

Typical Screening Intervals in Practice

When centers choose to screen high-risk populations:

• Annual anal cytology is the most common interval used in practice settings. 2
• Abnormal results (ASC-US, LSIL, or HSIL) trigger referral to HRA with biopsy. 1, 2

Risk Stratification for Screening Consideration

The CDC identifies distinct risk levels based on incidence rates per 100,000 person-years:

• MSM with HIV infection: 80-131 cases (highest risk, screening consideration starting age 35). 2, 4
• Men with HIV infection: 40-60 cases (screening consideration starting age 45). 2, 4
• Women with HIV infection: 20-30 cases (screening consideration starting age 45). 2, 4
• MSM without HIV infection: 14 cases (screening consideration starting age 45). 2, 4
• General population: 1-2 cases (no screening recommended). 1

Critical Limitations of Anal Cytology

Test Performance Issues

Anal cytology has limited sensitivity (55-89%) and specificity (40-67%) for detecting high-grade squamous intraepithelial lesions (HSIL). 1 This poor test performance is a major reason for the lack of official screening recommendations.

HPV Testing Not Useful

HPV testing is not clinically useful for anal cancer screening due to extremely high prevalence of anal HPV infection in high-risk populations, particularly MSM (61-93% prevalence). 1, 5 HPV16 is detected in 29% of HIV-positive MSM, making it too common to serve as a screening tool. 6

Important Clinical Caveats

Natural History Uncertainty

• HSIL may spontaneously regress without treatment in some cases. 1
• No definitive evidence exists that treating HSIL reduces anal cancer incidence or mortality. 1
• An ongoing clinical trial (NCT02135419) is investigating whether HSIL treatment reduces anal cancer incidence in persons with HIV. 1

Treatment Considerations

If HSIL is detected and treated:

• Recurrence rates are high: approximately 50% at 1 year and 77% at 3 years. 1
• Multiple treatment modalities exist (ablation, topical therapies), but none prevent recurrence reliably. 1

Practical Algorithm for Clinical Decision-Making

For HIV-positive MSM or persons with receptive anal intercourse:

1. Perform annual DARE starting in early-to-mid 30s. 1, 2
2. If practicing at a center with HRA capability, consider annual anal cytology. 1, 2
3. Refer abnormal cytology to HRA with biopsy. 2
4. Discuss risks/benefits given uncertain impact on mortality. 1

For HIV-positive heterosexual men/women:

• Annual DARE starting age 45. 2
• Consider cytology only if HRA available and patient desires screening after informed discussion. 1

For HIV-negative individuals without high-risk behaviors:

• No routine screening recommended. 1