The term Atypical Squamous Cells of Undetermined Significance, or ASCUS, is the most common abnormal finding from cervical screening. ASCUS is generally not a diagnosis of cancer, but a preliminary finding indicating minor cellular changes that warrant further investigation. ASCUS serves as a flag that requires follow-up testing to determine the cause and rule out the presence of a more significant underlying condition.
Defining Atypical Squamous Cells of Undetermined Significance
A diagnosis of ASCUS means that the squamous cells, the flat, thin cells lining the outer cervix, display changes that are not entirely normal, or “atypical”. These cellular variations in size, shape, or nuclear characteristics are more pronounced than those caused by simple irritation or inflammation, but they do not meet the definitive criteria for a low-grade or high-grade lesion.
The “undetermined significance” part of the diagnosis reflects the pathologist’s inability to definitively determine the cause or future implication of these subtle changes. ASCUS is the most frequently reported abnormal finding, accounting for approximately 2% to 5% of all Pap tests in the United States.
This diagnostic uncertainty arises because various factors can cause atypical cell changes, including infections, hormonal fluctuations, or even benign growths like cysts. This ambiguity necessitates the standardized follow-up protocol to stratify the patient’s risk.
The Link Between ASCUS and HPV
Persistent infection with the Human Papillomavirus (HPV) is the primary driver behind most cervical cellular changes, including ASCUS. HPV is a common virus, and certain types are classified as high-risk because of their potential to cause precancerous lesions and ultimately cancer. Approximately 40% to 50% of women who receive an ASCUS result are found to be infected with one of these high-risk HPV types.
HPV types 16 and 18 are responsible for the majority of cervical cancers and are therefore the most concerning high-risk types. The distinction between high-risk and low-risk HPV is crucial for risk assessment and management, as the low-risk types typically cause benign changes like genital warts.
For most people, an HPV infection is transient, meaning the body’s immune system clears the virus naturally within one to two years. If the infection is not cleared, it becomes persistent, and this prolonged presence of high-risk HPV significantly increases the risk of cellular changes progressing to high-grade lesions.
If the ASCUS result is found to be HPV-negative, the five-year risk of high-grade lesions is extremely low, similar to that of a woman with a completely normal Pap test. This is why the HPV status is important; it serves as a powerful risk stratifier, determining which ASCUS cases are likely benign and which require more immediate intervention.
Next Steps Following an ASCUS Diagnosis
The management of an ASCUS diagnosis is determined by current medical guidelines, which are primarily focused on assessing the presence of high-risk HPV. For women aged 25 to 65, the preferred management strategy is reflex HPV testing, where the same cell sample collected for the Pap test is analyzed for high-risk HPV DNA. This approach efficiently determines the patient’s risk profile without requiring a second appointment.
If the reflex HPV test is negative for high-risk types, the risk of having a significant lesion is considered very low, and the patient can return to routine screening, typically in three to five years. If the HPV test is positive, the risk of underlying precancerous changes is elevated, which prompts the next step: a colposcopy. The risk of high-grade disease (CIN 2 or worse) in women with HPV-positive ASCUS can be up to 20%.
Colposcopy involves a magnified, illuminated examination of the cervix using a specialized instrument, allowing the clinician to visually inspect the tissue for abnormal areas. If suspicious areas are identified, a small tissue sample, or biopsy, is taken for a definitive diagnosis. For women aged 21 to 24, a repeat Pap test at 12 months is often preferred over immediate HPV testing, as younger women frequently clear the virus naturally.