What are the next steps for a patient with an anal lesion that turns white with 3% acetic acid application, particularly in high-risk populations such as those with a history of Human Papillomavirus (HPV) infection, immunosuppressed patients, or men who have sex with men?

Management of Acetowhite Anal Lesion

An anal lesion that turns white with 3% acetic acid application requires biopsy under high-resolution anoscopy (HRA) to exclude high-grade squamous intraepithelial lesion (HSIL) or invasive anal cancer, particularly in high-risk populations. 1

Immediate Next Steps

Targeted biopsy of the acetowhite lesion is mandatory to exclude invasive disease. 1 The acetowhitening indicates abnormal epithelium that requires histopathological confirmation, as visual appearance alone cannot distinguish between low-grade lesions, HSIL, or early invasive cancer. 1

Key Clinical Actions:

• Perform HRA-guided biopsy of all acetowhite lesions, as this is the primary method for diagnosing HSIL and superficially invasive squamous carcinoma that may not be palpable on digital anorectal examination. 1

• Document lesion characteristics including location, tinctorial pattern (dense vs. faint), relief (flat vs. raised), surface (smooth vs. granular), and vascular pattern, as these features may help predict histologic grade. 2

• Ensure referral pathway exists before initiating any screening program, as cytology-based screening should only be performed if HRA and biopsy capabilities are available. 1

Risk Stratification

The clinical significance and urgency depend heavily on patient risk factors:

High-Risk Populations Requiring Aggressive Evaluation:

• HIV-positive patients (15-35 fold increased anal cancer risk compared to general population) 3
• Men who have sex with men (MSM), particularly HIV-positive MSM (incidence 131 per 100,000 person-years) 3
• Immunosuppressed patients (transplant recipients, chronic immunosuppression) 1
• Women with history of HPV-related anogenital malignancies (cervical, vulvar, or vaginal intraepithelial neoplasia) 1
• History of receptive anal intercourse 1

In these populations, progression from HSIL to invasive malignancy is more likely, particularly influenced by HIV seropositivity, low CD4 count, and HPV serotype. 1

Diagnostic Workup

Essential Components:

• Complete HRA examination with systematic visualization of the squamocolumnar junction, transformation zone, and perianal skin using colposcope magnification after 3% acetic acid application. 4, 5

• Biopsy all suspicious acetowhite lesions under local anesthesia, as HRA without biopsy identifies only a small percentage of true high-grade lesions. 4

• Consider Lugol's iodine solution application after acetic acid to improve lesion characterization. 4, 5

• HIV testing should be considered in patients with unknown status presenting with anal lesions, particularly if recurrent or multifocal. 1

• Screen female patients with anal intraepithelial neoplasia for synchronous cervical, vulvar, and vaginal intraepithelial neoplasia, as these HPV-related lesions frequently occur together. 1

Important Caveat About Screening Tests:

Do not rely on HPV testing alone for risk stratification, as high-risk HPV types have extremely high prevalence (91% in HIV-positive MSM, 57% in HIV-negative MSM) and are not clinically useful for anal cancer screening. 1, 6 Similarly, anal cytology has limited sensitivity (55-89%) and specificity (40-67%) for detecting HSIL. 1

Management Based on Histology

If Biopsy Shows HSIL:

Shared decision-making about treatment is recommended given high recurrence rates (50% at 1 year, 77% at 3 years) with all treatment modalities and evidence that some HSIL may spontaneously regress. 1

Treatment options include:

• Ablative methods: laser, electrocautery, or infrared coagulation
• Topical therapies: imiquimod (patient-applied)
• Observation: may be appropriate in select cases given spontaneous regression potential 1

If Biopsy Shows Low-Grade Lesions:

Progression from low-grade anal intraepithelial neoplasia to high-grade disease is uncommon in immunocompetent patients, though more likely in immunosuppressed individuals. 1

If Biopsy Shows Invasive Cancer:

Histological confirmation is mandatory as other pathologies are possible including adenocarcinoma, melanoma, gastrointestinal stromal tumors, poorly differentiated neuroendocrine tumors, and lymphoma. 1 Management follows standard anal cancer protocols with chemoradiotherapy as primary treatment for most cases.

Common Pitfalls to Avoid

• Do not assume benign pathology based on acetowhitening alone—biopsy is mandatory. 1

• Do not perform cytology-based screening without established HRA referral pathways, as this creates diagnostic limbo for patients with abnormal results. 1

• Do not overlook the learning curve for HRA—this is a challenging examination requiring specific training and equipment, ideally performed in reference centers with multidisciplinary teams. 4, 5

• Recognize HRA limitations: sensitivity is 90% but specificity only 19% in some studies, meaning many acetowhite lesions will not represent true HSIL on biopsy. 2

• Do not delay evaluation in high-risk populations, as anal cancer incidence begins increasing after early 30s and continues with age. 1