A Pap test result indicating abnormal cell changes on the cervix often leads to a diagnosis requiring follow-up. The two most common findings are Atypical Squamous Cells of Undetermined Significance (ASCUS) and Low-Grade Squamous Intraepithelial Lesion (LSIL). These results signify that cells collected during cervical screening appear different from healthy tissue. Understanding the distinction between these diagnoses is key to navigating medical management, which is standardized by the Bethesda System for reporting cervical cytology results.
What the Cytology Means: ASCUS vs. LSIL
ASCUS is considered the most frequently reported abnormal finding on a Pap test and represents a “morphologic uncertainty” at the cellular level. The term “Undetermined Significance” reflects that the cells show some minor irregularities, such as slightly enlarged nuclei, but these changes are not pronounced enough to definitively classify the finding as a clear precancerous lesion. This ambiguity means the pathologist cannot be certain if the changes are due to a temporary inflammation, a benign process, or a very early, low-grade infection.
In contrast, LSIL is a more definitive diagnosis, representing cellular changes that are clearly indicative of infection with the Human Papillomavirus (HPV). LSIL is cytologically classified as a low-grade lesion, which corresponds to Cervical Intraepithelial Neoplasia Grade 1 (CIN 1) when examined under a microscope. The cells show distinct features of the viral infection, including enlarged nuclei and a characteristic appearance called koilocytosis, where there is a clear, empty space or “halo” surrounding the nucleus.
The underlying cause for both ASCUS and LSIL is infection with the Human Papillomavirus (HPV). While HPV is often present in ASCUS, the cellular changes are less dramatic, giving ASCUS a lower risk of progression than LSIL. LSIL is recognized as a true lesion, and nearly all cases are associated with HPV, causing the specific observable changes in the cervical cells.
Follow-up and Management Protocols for ASCUS
The management of an ASCUS result is focused on risk stratification, which is primarily achieved by determining the patient’s underlying HPV status. The preferred method for triage is “reflex HPV testing,” where the laboratory tests the same sample used for the Pap test for the presence of high-risk HPV types. This strategy avoids the need for the patient to return for a separate follow-up appointment immediately.
If the reflex HPV test is negative for high-risk types, the risk of developing a serious lesion is extremely low, and the patient generally returns to routine screening. For women aged 30 and older, this means repeating the co-testing (Pap and HPV) in three years. If the high-risk HPV test is positive, however, the ASCUS finding is treated more seriously, as this combination indicates a higher likelihood of a persistent infection.
For women aged 25 or older with HPV-positive ASCUS, the standard follow-up is an immediate referral for colposcopy. Colposcopy is a procedure where a magnifying instrument is used to visually examine the cervix for abnormal areas. For younger women, specifically those aged 21 to 24, management is often more conservative, typically involving a repeat Pap test in 12 months rather than immediate colposcopy. This approach recognizes the high rate of spontaneous HPV clearance in this younger age group.
Standard Management and Treatment for LSIL
Management for LSIL generally requires a more structured approach than ASCUS because it confirms the presence of a viral-induced low-grade lesion. For most adult women, defined as those aged 25 and older, the standard of care is an immediate referral for colposcopy. The purpose of the colposcopy is to allow the clinician to identify the precise location and extent of the abnormal tissue and to take targeted biopsies to rule out any higher-grade disease that might be masked by the LSIL cytology.
An exception to this immediate referral protocol is made for adolescents and young women aged 21 to 24. In this demographic, the immune system is highly effective at clearing HPV, and LSIL is expected to regress without intervention in up to 90% of cases within two years. Therefore, the recommended protocol is observation, which involves repeating the Pap test in 12 months rather than proceeding directly to colposcopy.
If the repeat cytology remains abnormal after 12 months of observation, or if the initial LSIL finding is in a woman aged 25 or older, the colposcopy referral is activated. Management aims to avoid unnecessary medical procedures while effectively identifying the small subset of patients whose lesions are progressing. Since LSIL resolves naturally for the majority of patients, the strategy relies on careful, risk-based surveillance.

