ASC-US stands for “atypical squamous cells of undetermined significance.” It is a result on a Pap test (also called a Pap smear) that means some of the squamous cells collected from the surface of your cervix look slightly abnormal under the microscope. The changes are not clearly normal, but they are also not clearly precancerous, which is exactly what the phrase “undetermined significance” is meant to convey.
ASC-US is one of the most common abnormal Pap test results and, in most cases, does not mean cancer or a precancerous condition is present. However, because ASC-US can occasionally be caused by an early precancerous change, follow-up testing is usually recommended to make sure nothing more serious is missed. This article will help you understand what ASC-US means, why it happens, and what the next steps in your care are likely to be.
What causes ASC-US?
The most common cause of ASC-US is infection with human papillomavirus (HPV), particularly in people under the age of 30. However, many non-HPV conditions can also cause squamous cells to look slightly abnormal on a Pap test:
- HPV infection — High-risk types of HPV can cause subtle changes in the squamous cells lining the cervix. Most HPV infections clear on their own within one to two years, especially in younger people, and the cellular changes resolve along with the infection.
- Yeast or bacterial infections — Common vaginal infections such as candidiasis, bacterial vaginosis, or trichomoniasis can cause inflammation that alters the appearance of cervical cells.
- Inflammation or irritation — Inflammation from any cause — including an intrauterine device (IUD), recent intercourse, or minor trauma — can produce reactive changes that are read as ASC-US.
- Hormonal changes — Lower estrogen levels around and after menopause can cause the cells of the cervix to become thinner and less mature, an effect called atrophy. Atrophic cells can sometimes appear abnormal under the microscope.
- Recent childbirth or pregnancy — Hormonal and tissue changes during and after pregnancy can produce temporary cellular changes that may be read as ASC-US.
- Prior radiation therapy — Radiation to the pelvic area can cause long-lasting changes in the appearance of cervical cells.
- Normal cellular aging or regeneration — The squamous cells of the cervix are constantly being shed and replaced. Cells that are at different stages of this normal turnover process can occasionally look slightly atypical.
In many cases, the cellular changes that produce the ASC-US result resolve on their own without treatment, especially when they are caused by temporary factors such as infection or inflammation.
What does ASC-US look like under the microscope?
When a pathologist or a specially trained cytotechnologist examines the Pap test sample under the microscope, the cells in an ASC-US result show mild abnormalities — enough to stand out from normal squamous cells, but not enough to qualify as a clear precancerous lesion. The cells may show:
- Slightly enlarged nuclei — The nucleus (the part of the cell that holds the genetic material) is somewhat larger than expected for a normal squamous cell.
- Reduced cytoplasm — The cytoplasm (the body of the cell surrounding the nucleus) appears smaller relative to the size of the nucleus. This shift is called an increased nuclear-to-cytoplasmic ratio and is a common feature pathologists use to evaluate cellular abnormality.
- Slightly darker nuclei — The nuclei may appear darker than normal under the microscope, a feature called hyperchromasia.
- Mild irregularity of nuclear shape — The outline of the nucleus may be slightly uneven rather than smooth and rounded.
These features are mildly abnormal but are not severe enough to meet the criteria for a squamous intraepithelial lesion — the term used for a clearly precancerous change. When cells appear more abnormal than this but still do not fully meet the criteria for a precancerous lesion, the result is reported as ASC-H, which carries a higher level of concern.
How is ASC-US different from ASC-H?
ASC-US and ASC-H are both “atypical squamous cell” Pap test results, but they differ in how concerning the changes are and how they should be followed up. ASC-US describes mildly atypical cells and is associated primarily with the risk of low-grade squamous intraepithelial lesion (LSIL). Most ASC-US results resolve on their own, and follow-up may involve only repeat Pap testing or HPV testing, depending on age and circumstances.
ASC-H, by contrast, raises specific concern for high-grade squamous intraepithelial lesion (HSIL) — a more serious precancerous condition. The abnormal cells in ASC-H are more worrisome than those in ASC-US, and colposcopy is recommended for almost all ASC-H results, regardless of HPV test status.
What happens after an ASC-US result?
Most people with ASC-US do not need immediate treatment. The next step depends mainly on your age and on whether HPV testing was performed alongside the Pap test or can be done now on the same sample.
For people aged 30 and older, the standard approach is reflex HPV testing — using the same sample to look for high-risk HPV types. The result of this test largely determines the next step:
- HPV-negative ASC-US — The risk of an underlying precancerous lesion is low. Most current guidelines recommend returning to routine cervical screening, with the next Pap test or HPV co-test in three to five years, depending on the local screening protocol.
- HPV-positive ASC-US — The likelihood that an underlying precancerous lesion is present is higher. A colposcopy — an examination of the cervix using a special magnifying instrument called a colposcope — is typically recommended so that any abnormal-looking area can be sampled with a biopsy.
For people under the age of 25, ASC-US is most often caused by transient HPV infections that the immune system clears on its own. In this group, repeat Pap testing in 12 months — rather than HPV testing or colposcopy — is generally recommended, since immediate intervention has not been shown to improve outcomes and may lead to unnecessary procedures.
If a colposcopy is performed and a biopsy is taken, the possible outcomes include:
- Biopsy is normal — No precancerous lesion is found. Follow-up with repeat Pap testing or HPV testing is usually recommended in 6 to 12 months.
- Biopsy shows LSIL or CIN1 — A low-grade precancerous change is found. This usually resolves on its own and is typically managed with close monitoring rather than immediate treatment.
- Biopsy shows HSIL (CIN2 or CIN3) — A higher-grade precancerous lesion is found. Treatment such as a loop electrosurgical excision procedure (LEEP) or cone biopsy is usually recommended to remove the abnormal area.
In the great majority of cases, ASC-US resolves on its own and does not cause any long-term problems. The most important thing is to follow your doctor’s recommendations for follow-up testing on the schedule that is right for your age and HPV status.
Questions to ask your doctor
- What does ASC-US mean for me, and how worried should I be?
- Was an HPV test performed alongside my Pap test, and what were the results?
- If my HPV test was positive, should I have a colposcopy now or wait and repeat the Pap test?
- If my HPV test was negative, when is my next Pap test or HPV test due?
- What is the chance that the cellular changes will go away on their own?
- Are there any non-HPV causes — such as menopause, infection, or inflammation — that could explain my result?
- How is ASC-US different from ASC-H, and which one do I have?
- If I am under 25, why is the recommendation different for me than for older patients?
- If a biopsy is needed, what are the possible findings and what would each one mean for my treatment?
- How often will I need follow-up testing, and for how long?
- Should I consider HPV vaccination if I have not already been vaccinated?
- Are there any symptoms I should watch for between scheduled appointments?
Related articles on MyPathologyReport.com