From the Guidelines
For a patient with HIV who has an anal Pap test negative for malignant cells but positive for high-risk HPV types (excluding HPV 16/18), I recommend repeating the anal cytology in 6-12 months. This follow-up interval balances surveillance needs with the understanding that many HPV infections clear spontaneously, as suggested by the most recent guidelines 1. The patient should continue regular HIV care with antiretroviral therapy to maintain immune function, as immunosuppression increases the risk of HPV persistence and progression.
Key considerations in managing this patient include:
- The higher risk of premalignant anal epithelial changes in people living with HIV (PLWH) compared to HIV-negative patients 1
- The importance of ongoing surveillance due to the increased risk of HPV persistence and progression to anal dysplasia and cancer in HIV-positive individuals
- The potential benefits of early detection and treatment of high-grade anal intraepithelial neoplasia (AIN) in preventing the development of anal cancer, although the spontaneous regression rate of high-grade AIN is not well understood 1
If subsequent testing shows persistent high-risk HPV or abnormal cytology, referral for high-resolution anoscopy (HRA) would be appropriate for direct visualization and possible biopsy of suspicious areas. This approach is supported by the latest clinical practice guidelines, which emphasize the importance of surveillance and early intervention in high-risk populations 1. While the current result doesn't indicate immediate concern for high-grade lesions (particularly since the most oncogenic types 16/18 are negative), continued monitoring is necessary due to the increased risk in the setting of HIV infection.
From the Research
Follow-up for Anal Pap with Negative Malignant Cells but Positive for HPV Other HR Types
- The patient is HIV positive and has an anal pap result that is negative for malignant cells but positive for HPV other high-risk (HR) types, negative for HPV 16 and HPV 18 2, 3.
- Given the high prevalence of HPV infection in HIV-positive men who have sex with men (MSM), anal HPV testing may lead to a high number of "false positives" 2.
- A screening program with anal cytology is proposed, which has a high sensitivity for detection of anal intraepithelial neoplasia (AIN) but is a poor predictor of the severity of these lesions 2.
- All patients with abnormal anal Pap smear should undergo anoscopy with biopsy 2.
Risk Factors and Screening
- HIV infection is one of the strongest risk factors for anal squamous cell cancer (ASCC), and most ASCC are caused by HPV, particularly HPV-16 3.
- Anal cytology has poor sensitivity and specificity, and high-resolution anoscopy (HRA) is advocated by some as a screening tool in high-risk groups 3.
- HPV vaccination and earlier start of combination antiretroviral therapy (cART) may prevent most anal cancers in the long run 3, 4.
HPV Testing and Triage
- HR-HPV testing can be used to triage patients with normal and atypical squamous cells of undetermined significance cytology for HRA, resulting in an algorithm with high sensitivity and specificity 5.
- The nonavalent HPV vaccine is effective in preventing the development of high-grade precancerous cervical lesions in noninfected patients, and vaccination is ideally administered at 11 or 12 years of age 4.