What are the next steps for a patient with Atypical Squamous Cells of Undetermined Significance (ASCUS) on a Papanicolaou (Pap) test with a negative Human Papillomavirus (HPV) result?

From the Guidelines

For ASCUS on Pap smear with negative HPV testing, the recommended next step is to repeat the HPV test with or without a concurrent Pap test in 3 years, as outlined in the 2019 ASCCP risk-based management consensus guidelines 1. This approach is based on the understanding that a negative HPV test result significantly reduces the risk of underlying high-grade disease, making immediate colposcopy or more intensive follow-up unnecessary for most patients. The management strategy prioritizes the balance between monitoring for potential development of cervical lesions and avoiding unnecessary procedures that could lead to harm or undue anxiety for the patient.

Key considerations in managing ASCUS with negative HPV include:

• The patient's screening history and previous results, as these can influence the risk assessment and management plan.
• The presence of any symptoms such as abnormal vaginal bleeding, which might necessitate earlier evaluation regardless of the screening schedule.
• Adherence to age-appropriate screening guidelines, recognizing that the risk of cervical cancer and the effectiveness of screening strategies can vary by age.

According to the guidelines 1, the preference for repeating the HPV test (with or without a Pap test) in 3 years reflects a risk-based approach that aims to minimize harm while ensuring that individuals at higher risk of developing cervical cancer are identified and managed appropriately. This strategy is supported by evidence indicating that the risk of progressing to high-grade cervical lesions or cancer is low in the context of a negative HPV test result, even with an ASCUS Pap smear finding 1.

From the Research

Next Steps for ASCUS on Pap with Negative HPV

• The management of patients with atypical squamous cells of undetermined significance (ASCUS) on a Pap test and a negative human papillomavirus (HPV) test result is a topic of interest in gynecology 2, 3, 4, 5, 6.
• According to a study published in JAMA, HPV DNA testing of residual specimens collected for routine cervical cytology can help identify those who have underlying high-grade squamous intraepithelial lesions (HSIL) 2.
• Another study published in The Journal of family practice suggests that women with ASCUS and particularly low-grade squamous intraepithelial lesion (LSIL) Pap smears should be referred for a colposcopy examination until better triage methods become available 3.
• A study published in Clinical and experimental obstetrics & gynecology found that HPV DNA examination is an effective means of categorizing and managing ASCUS, and the rate of detection of high-risk HPV was higher than among patients who had not undergone HPV detection and among patients who were negative for HPV 4.
• The results of a retrospective study published in Diagnostic cytopathology correlated the results of conventional cervical cytology, colposcopy guided biopsy, and cold knife conization (CKC) procedures, and found that conventional cytology had a sensitivity of 70.8% and a specificity of 62.2% for the detection of low-grade lesions, while it had a sensitivity of 72.4% and a specificity of 86.0% for the detection of high-grade lesions 5.
• A study published in Virology journal found that the use of local estrogen therapy in post-menopausal women with ASCUS and positive HPV test results increased the specificity of the test, and suggests that the HPV test should be used as the first diagnostic possibility in cases of ASCUS in post-menopausal women, associating local estrogen therapy only with HPV positive women 6.

Considerations for Clinical Practice

• The American College of Obstetricians and Gynecologists (ACOG) recommends that women with ASCUS and a negative HPV test result should have a repeat Pap test in 3 years 2.
• However, the optimal management strategy for women with ASCUS and a negative HPV test result is still a topic of debate, and may depend on individual patient factors and clinical judgment 3, 4, 5, 6.
• Colposcopy and biopsy may be considered for women with ASCUS and a negative HPV test result, especially if there are other risk factors for cervical cancer or if the patient has a history of abnormal Pap test results 3, 5.