A result of “Atypical Squamous Cells” (ASC) comes from a cervical screening test, commonly known as a Pap test, and signals that some cells collected from the cervix appear unusual under a microscope. This finding is common, but ASC rarely indicates the presence of cervical cancer. “Atypical” is a broad term meaning the cells show changes that are not completely normal, but are also not clearly defined as a more serious precancerous lesion. Identifying ASC flags the need for follow-up testing to determine the exact cause of these subtle cellular changes.
Understanding Squamous Cells and Atypia
Squamous cells are the flat, thin cells that cover the outer surface of the cervix, the lower part of the uterus that opens into the vagina. These cells form a protective layer, and a Pap test collects a sample to check for abnormalities. The term “atypia” refers to slight changes in the size, shape, or growth pattern of these cells that deviate from their normal appearance.
Atypical cells show abnormalities more noticeable than simple reactive changes, such as those caused by inflammation, but they do not meet the full criteria for being labeled a precancerous lesion. ASC can be caused by various factors, and medical evaluation aims to distinguish between harmless changes and those requiring closer monitoring.
Classifications and Severity of Atypical Cells
The medical community uses the Bethesda System to classify and report Pap test results, which includes two distinct ASC classifications. This distinction dictates the urgency and type of follow-up care required. These classifications help providers assess the risk that a more serious condition is present or may develop.
The most frequent abnormal finding is Atypical Squamous Cells of Undetermined Significance (ASC-US), which accounts for approximately 5-10% of all reported Pap smears. This result means that the cell changes are minor and the pathologist cannot definitively determine if the cause is benign, such as inflammation, or if it is related to a low-grade precancerous lesion. A significant portion of ASC-US cases, sometimes more than half, are likely to resolve on their own without intervention. However, an estimated 10-15% of individuals with an ASC-US result may have an underlying moderate to severe precancerous lesion.
The second, less common classification is Atypical Squamous Cells—Cannot Exclude High-Grade Squamous Intraepithelial Lesion (ASC-H). This result is used when the abnormal cells show features that are suggestive of a more serious, high-grade lesion, though they still do not fully meet the diagnostic criteria for it. The distinction from ASC-US is based on the appearance of the cells, which look more concerning for a possible pre-cancer. This classification carries a significantly higher risk, with studies estimating that an underlying moderate or severe precancerous lesion is found in 30-40% of ASC-H cases.
Underlying Causes of an ASC Result
The most common reason for atypical cell changes is infection with the Human Papillomavirus (HPV), particularly high-risk types. Persistent infection with high-risk HPV is the direct cause of nearly all cases of cervical precancer and cancer. Studies show that high-risk HPV is detected in 45% to over 60% of ASC-US cases.
Not all ASC results are linked to HPV, as changes can also be caused by non-viral factors. Inflammation of the cervix (cervicitis), resulting from yeast or bacterial infections, can alter the appearance of squamous cells.
Hormonal changes, particularly low estrogen levels in post-menopausal individuals, can lead to cell changes interpreted as atypical. Other benign factors, such as cervical cysts or polyps, or issues with the sample collection itself, can also contribute to an ASC finding.
Follow-up Testing and Management
Follow-up steps depend on the specific ASC classification received, as the two categories represent different risk levels. For the most common finding, ASC-US, the primary strategy involves testing for high-risk HPV. This approach, called “reflex HPV testing,” uses the same Pap test sample to determine if the high-risk virus is present. If the HPV test result is negative, the risk of a serious lesion is low, and the patient typically returns to routine screening in three years.
If the ASC-US result is positive for high-risk HPV, or if HPV testing is not available, a more intensive follow-up procedure is recommended. This usually involves a procedure called a colposcopy, which is a magnified visual examination of the cervix. For the more concerning classification of ASC-H, the standard management is to bypass HPV testing and proceed directly to a colposcopy.
During a colposcopy, a provider uses a specialized microscope to look for abnormal tissue areas that might require a biopsy. For ASC-H, management is aggressive due to the higher likelihood of an underlying high-grade precancerous lesion. Follow-up strategies ensure that developing precancerous cells are detected and treated before they progress to cervical cancer.

