What Does ASCUS Mean on a Pap Test?

ASCUS stands for “atypical squamous cells of undetermined significance,” and it is the most common abnormal result on a Pap test. It means the lab found cervical cells that look slightly different from normal but not clearly abnormal enough to call a precancerous lesion. The word “undetermined” is doing a lot of work here: the cells could look off because of an infection, inflammation, hormonal changes, or nothing at all, but they could also be an early sign of something that needs closer attention. What happens next depends almost entirely on whether high-risk HPV is involved.

Why the Cells Look Different

Under a microscope, the cells flagged as ASCUS show subtle changes in their nuclei, such as slightly enlarged size, mild irregularity in shape, or faintly darker staining than expected. These features fall into a gray zone. They are not clearly normal, but they do not meet the threshold for a definite low-grade or high-grade squamous intraepithelial lesion (the categories that signal a precancerous change).¹ Think of ASCUS as the pathologist saying, “Something caught my eye, but I can’t tell you what it means yet.”

Many things can cause cells to look mildly atypical without any precancerous process happening at all. Cervical erosion (where the inner lining of the cervical canal extends outward) is a common trigger. Yeast infections, bacterial imbalances, and other sexually transmitted organisms can inflame the tissue enough to change how cells appear on a slide.² Even the mechanical act of collecting the sample can distort cells slightly. So an ASCUS result on its own is not an alarm bell.

How Menopause Complicates the Picture

If you are postmenopausal, ASCUS results deserve a bit of extra context. When estrogen levels drop after menopause, the cervical lining thins out. The remaining cells are smaller and more immature, with a naturally higher ratio of nucleus to surrounding cell body. That mimics exactly what a pathologist looks for when flagging abnormal cells.³ In other words, low estrogen alone can produce an ASCUS reading in the absence of any disease. The same hormonal shift also disrupts the vaginal microbiome, making infections more common and further muddying the picture.

Some clinicians use a short course of topical estrogen cream before repeating the Pap test. If the “atypia” was really just thinning from low hormones, the cells often look normal once estrogen restores the tissue.⁴ This is a useful trick that helps separate harmless atrophy from a genuine precancerous change without rushing to a biopsy.

The HPV Test That Decides What Happens Next

For most people, an ASCUS result triggers what is called reflex HPV testing. The lab already has your sample (collected at the same time as the Pap), so no additional appointment is needed. They simply run it through a molecular test that checks for high-risk strains of human papillomavirus, the virus responsible for virtually all cervical cancers.⁵

If HPV comes back negative, you can exhale. The five-year risk of a serious precancerous lesion (called CIN3 or worse) for someone with ASCUS but no high-risk HPV is under half a percent, and the risk of actual cancer is extremely low.⁶ For these women, routine screening at the normal interval is generally all that’s recommended.

If HPV comes back positive, the story changes. Five-year risk of CIN3 or worse among HPV-positive women with ASCUS is roughly 7%, which is actually slightly higher than for women diagnosed with the next step up, low-grade squamous intraepithelial lesion (LSIL).⁶ That finding surprises many people: the “undetermined significance” label makes ASCUS sound less worrying than LSIL, but when high-risk HPV is on board, ASCUS carries a comparable or even modestly higher risk. The standard recommendation for HPV-positive ASCUS is colposcopy, a closer look at the cervix under magnification, usually with directed biopsies.

Why HPV Type 16 and 18 Get Special Attention

Not all high-risk HPV strains carry the same weight. Types 16 and 18 are responsible for the majority of cervical cancers, and women with ASCUS who test positive for these two strains face substantially higher odds of having a significant lesion already present. One study found that women with ASCUS and HPV 16 or 18 had a rate of high-grade lesions roughly double that of women with ASCUS carrying other high-risk HPV types.⁷ Another analysis estimated that having HPV 16 and/or 18 increased the odds of a CIN2-or-worse lesion roughly sixfold compared to other strains.⁸

This is why some labs now report genotyping alongside the HPV result. If your report says “HPV 16 detected” or “HPV 18 detected,” your clinician will almost certainly recommend colposcopy promptly, regardless of how mild the Pap abnormality looks. If the HPV is positive but for a non-16/18 strain, the risk is lower, though still elevated enough that follow-up is warranted.

What Current Guidelines Recommend

Management of ASCUS has evolved over the years, and the current U.S. approach is risk-based rather than result-based. The 2019 ASCCP consensus guidelines (updated through 2023) estimate your risk of a serious lesion by combining your Pap result, HPV status, and screening history. For someone aged 25 or older screened with cytology alone, persistent ASCUS or a positive HPV result after an ASCUS finding generally leads to a colposcopy recommendation. If a colposcopy was previously recommended but not completed, and repeat testing shows the HPV has cleared and cytology is normal, it may be acceptable to retest in a year rather than proceed with colposcopy.⁹

The shift toward risk-based management is significant because it means the same Pap result can lead to different next steps for different people. A 28-year-old with a first-time ASCUS and negative HPV is in a very different situation from a 55-year-old with ASCUS, positive HPV 16, and a history of prior abnormal results. The guidelines are designed to avoid both under-treatment (missing a lesion that could progress) and over-treatment (putting low-risk people through unnecessary biopsies).

ASCUS During Pregnancy

Getting an ASCUS result while pregnant is understandably unsettling, but pregnancy does not change the nature of the finding, and it usually does not require aggressive workup. A study examining colposcopy during pregnancy for women with minimally abnormal Pap results found that the procedure did not meaningfully change management: the pregnancies and outcomes were similar whether or not colposcopy was performed.¹⁰ Most clinicians will defer follow-up until the postpartum period. Cervical precancers, even when present, progress slowly enough that a delay of several months for delivery poses very little added risk. Colposcopy can be done during pregnancy if there is strong suspicion of a high-grade lesion, but treatment (like excision) is almost never performed until after delivery.

The Subjectivity Problem

One thing most people don’t realize about ASCUS is how subjective the diagnosis is. Pathologists looking at the same slide frequently disagree about whether cells qualify as ASCUS, normal, or a definite low-grade lesion. In the large ASCUS-LSIL Triage Study (ALTS), quality-control reviewers agreed with the original ASCUS reading only about 43% of the time, and most of the disagreements were in the direction of downgrading the cells to normal.¹¹ Another study found complete agreement among multiple reviewers on ASCUS cases only about 14% of the time.¹²

This doesn’t mean the diagnosis is useless. It means ASCUS is a genuinely borderline call, and the system acknowledges that by building in a safety net (the HPV reflex test). The HPV result is far more reproducible than the cytology reading and is the real driver of what happens next. If the Pap were the final word, this level of disagreement would be a serious problem. Because the HPV test sorts out who actually needs follow-up, the built-in fuzziness of ASCUS is tolerable.

The Emotional Weight of an Abnormal Result

Even though ASCUS is the mildest possible abnormal Pap finding, it tends to cause real anxiety. A German survey found that roughly 70% of women with abnormal Pap results reported being at least moderately concerned, and more than a quarter described themselves as severely concerned.¹³ The worry intensifies when HPV testing is added: women who tested positive for high-risk HPV had significantly higher anxiety, cancer worry, and overall psychological burden than those who tested negative.¹⁴

Part of the distress comes from the language itself. “Atypical cells” and “undetermined significance” sound ominous in a medical context even though they translate to “we’re not sure.” Add the HPV connection, with its association with sexually transmitted infection and cancer, and it’s easy to spiral. If you’ve received this result and feel anxious, that reaction is extremely common. It can help to remember two things: the vast majority of ASCUS results, even HPV-positive ones, do not lead to cancer; and the follow-up process exists precisely to catch the small number that need treatment long before cancer could develop.

Follow-Up Matters More Than the Result Itself

The biggest risk factor with ASCUS is not the cells on the slide. It’s whether a person follows up. In one U.S. cohort, roughly 28% of women with an initial ASCUS diagnosis were lost to follow-up entirely. Among those who did return, some underwent repeat Pap testing while others went straight to colposcopy, depending on clinical judgment. The follow-up pathway matters because precancerous lesions caught early are almost always treatable, while those that slip through the cracks because someone didn’t come back can progress over years.

Research consistently shows that follow-up adherence is not equally distributed. Black women in one study were significantly more likely to be non-adherent with recommended follow-up compared to white women, and patients with private insurance were far more likely to return for care than those who were uninsured or underinsured.¹⁵ Barriers to follow-up among Latina women referred for colposcopy included language, transportation, fear of the procedure, and lack of understanding about why it was needed.¹⁶ These are systemic problems, not individual failures, and they contribute to the persistent disparities in cervical cancer incidence and mortality.

ASCUS Versus ASC-H

You may notice a related term on lab reports: ASC-H, which stands for “atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion.” Both ASCUS and ASC-H fall under the umbrella of atypical squamous cells, but they carry very different implications. ASCUS leans toward the possibility of a low-grade process or nothing at all. ASC-H means the pathologist sees features that raise concern for a high-grade lesion but can’t be certain.¹ ASC-H is much less common than ASCUS but leads to colposcopy in nearly every case, regardless of HPV status. If your report says ASC-H rather than ASCUS, the follow-up will be more urgent.

How HPV Vaccination Affects ASCUS Rates

You might expect widespread HPV vaccination to reduce abnormal Pap results across the board, and it does reduce the most worrying findings. In a Danish registry study comparing birth cohorts screened before and after routine vaccination became available, the rate of high-grade lesions (HSIL) dropped significantly in the vaccinated cohort. But the rate of ASCUS itself actually went up slightly.¹⁷ The researchers attributed this partly to a simultaneous switch from conventional Pap smears to liquid-based cytology, which can detect more borderline abnormalities. The important takeaway is that vaccination dramatically reduces the serious findings that lead to cancer, even if it doesn’t eliminate the ambiguous ASCUS reading. Getting vaccinated doesn’t mean you’ll never see ASCUS on a report, but it does mean the result is less likely to signal something dangerous.

Putting the Numbers in Perspective

The data from the ASCUS-LSIL Triage Study remains some of the most robust on how these mild abnormalities play out. Among women who tested positive for high-risk HPV, the risk of a serious precancerous lesion (CIN3) over two years of follow-up was about 11% for those with ASCUS or LSIL, compared to 45% for those with a high-grade reading (HSIL).¹⁸ Women who tested HPV-negative were at low risk regardless of their cytology result. These numbers illustrate the central pattern: the HPV result matters more than the Pap result.

Among HPV-positive women with ASCUS or LSIL followed for up to four and a half years, roughly 29% of the ASCUS group showed moderate-or-worse lesions on biopsy, while about 11% had high-grade (CIN3) lesions.¹⁹ That 29% sounds high, but keep in mind this is the subgroup already known to be HPV-positive. The overall population of women who receive an ASCUS result includes a large majority who are HPV-negative and face minimal risk. When you fold everyone together, the chances that an ASCUS result leads to something requiring treatment are relatively small, and the chances of it being cancer are very small indeed.

The screening and triage system is designed so that no single test result determines your fate. ASCUS is the first flag in a chain of evidence-gathering. If HPV testing, genotyping, colposcopy, and biopsy are each done when indicated, the system catches precancerous changes at a stage where they can be treated simply and effectively, often with a brief outpatient procedure. The real danger is not in getting an ASCUS result. It’s in not completing the follow-up that the result sets in motion.