What Causes an ASCUS Result on a Pap Smear?

An ASCUS result means the lab saw a few cervical cells that look slightly off but couldn’t decide what the change means. It describes a doubt rather than a diagnosis. The cause is often the HPV virus, but irritation from infections, low estrogen after menopause, and the subjectivity of reading slides can all produce the same picture. That is why the next step is usually a test to find out which of these is behind it, not treatment.

What the Lab Actually Saw

Your report may say ASC-US, short for atypical squamous cells of undetermined significance. “Squamous” refers to the flat surface cells that line the outside of the cervix, the area a Pap test is designed to sample. A separate, more concerning category, ASC-H, means the lab can’t rule out a high-grade change.1OBG Management. Managing ASCUS and AGUS Pap smears ASCUS is the milder of the two, and it makes up about 90% of atypical cell results.2Journal of Clinical and Translational Pathology. Updates in Cervical Cancer Screening Guidelines, The Bethesda System for Reporting Cervical Cytology, and Clinical Management Recommendations

Under the microscope, the cells’ centers (nuclei) look 2 to 3 times larger than a normal cell’s, with only small changes in shape or color.3Journal of Clinical and Translational Pathology. Updates in Cervical Cancer Screening Guidelines, The Bethesda System for Reporting Cervical Cytology, and Clinical Management Recommendations The change hints at a mild cell change but isn’t clear enough to call it one.4Journal of Clinical and Translational Pathology. Updates in Cervical Cancer Screening Guidelines, The Bethesda System for Reporting Cervical Cytology, and Clinical Management Recommendations The word “atypical” describes how the cells look, not a disease.

It also differs from the results just above it. LSIL means a clear mild change, usually from HPV, and HSIL means a clear serious precancer change. ASCUS means the cells fit neither confidently, so it is a question mark rather than a lower grade of disease.

HPV, the Most Common Cause

In large labs testing ASCUS samples, high-risk HPV (human papillomavirus, the virus behind most cervical precancer) was found in about 34%.5PubMed. Reflex high-risk human papillomavirus testing for women with atypical squamous cells of undetermined significance in cytologic smears: effects since implementation in a large clinical practice The share climbs as results get more serious, to about 87% in high-grade changes.6PubMed Central. Prevalence of human papillomavirus infection in abnormal pap smears So in most ASCUS results, something other than high-risk HPV is the likely cause.

Age changes the odds. About 58% of women 20 or younger with ASCUS carry high-risk HPV,7PubMed. Reflex high-risk human papillomavirus testing for women with atypical squamous cells of undetermined significance in cytologic smears: effects since implementation in a large clinical practice but that drops to about 15% in women over 35.8PubMed. Reflex high-risk human papillomavirus testing for women with atypical squamous cells of undetermined significance in cytologic smears: effects since implementation in a large clinical practice HPV infections are very common in young people, and most clear on their own within a year or two. Many are picked up soon after becoming sexually active. While the virus is active, it can make cervical cells look briefly irritated, which is how a passing infection produces an ASCUS reading. This is also why doctors are more cautious about acting fast on ASCUS in the early twenties, when most changes resolve by themselves.

Among women with ASCUS who carried a high-risk type, type 16 was by far the most common.9PubMed Central. The Most Common Type of HPV in Women with Atypical Squamous Cell of Undetermined Significance (ASCUS) in Pap Smear in Iran-Yazd It gets singled out because it is the high-risk type most strongly linked to cervical precancer and cancer. Low-risk types 6 and 11, which cause genital warts, can also appear.10PubMed Central. The Most Common Type of HPV in Women with Atypical Squamous Cell of Undetermined Significance (ASCUS) in Pap Smear in Iran-Yazd They aren’t part of standard high-risk testing and aren’t the types that lead to cervical cancer. A positive HPV result can’t reveal when or from whom the virus came, since it can stay silent for years.

Infections and Inflammation

Trichomonas, a common sexually transmitted parasite, can make cells look like ASCUS even with no HPV at all.11PubMed Central. Association of Trichomonas vaginalis and Cytological Abnormalities of the Cervix in Low Risk Women In those cases the result is essentially a false alarm that can lead to needless worry and procedures.12PubMed Central. Association of Trichomonas vaginalis and Cytological Abnormalities of the Cervix in Low Risk Women Other infections play a role too. In over 9,000 women, bacterial vaginosis and gonorrhea raised the chance of ASCUS even after accounting for HPV.13PubMed Central. Associations of sexually transmitted infections and bacterial vaginosis with abnormal cervical cytology: A cross-sectional survey with 9090 community women in China Yeast and an imbalanced vaginal bacteria mix made ASCUS about 1.4 times more likely on the next smear.14PubMed. Candida and dysbacteriosis: a cytologic, population-based study of 100,605 asymptomatic women concerning cervical carcinogenesis

The reason is inflammation. An infection leaves the cervix inflamed, and inflamed cells can swell and show larger, darker centers that look like early abnormal change. Inflammation also makes the reading less certain, because cells changing for harmless reasons resemble those changing for worrying ones. That is why ASCUS from an infection can disappear once the infection clears, with no trace of HPV or precancer.

Bacterial vaginosis can matter beyond the smear. In women with high-risk HPV, those with bacterial vaginosis cleared the virus less often, 29% versus 52%,15PubMed Central. Bacterial vaginosis in microscopic examination of Pap smears in patients with high-risk HPV is associated with viral persistence and cytological progression in a longitudinal study and their Pap results worsened more often, 24% versus 10%.16PubMed Central. Bacterial vaginosis in microscopic examination of Pap smears in patients with high-risk HPV is associated with viral persistence and cytological progression in a longitudinal study So if you have HPV and bacterial vaginosis, it’s worth asking about treatment.

Unusual discharge, a fishy odor, itching or burning suggest bacterial vaginosis, yeast or trichomonas. But many of these infections cause no symptoms at all. Tell your clinician about any symptoms around the time of the test, and ask whether infection testing was done or is needed.

If an infection is found, most are treated with a short course of medicine. Partners may need treatment for trichomonas or gonorrhea. A repeat test after treatment often comes back normal, though treatment doesn’t replace your recommended follow-up. Finding an infection doesn’t rule out HPV; you can have both, so complete any HPV test in your follow-up.

Menopause and Low Estrogen

After menopause, estrogen drops and the cervical lining becomes thinner.17PubMed Central. Analysis of the related factors of atypical squamous cells of undetermined significance (ASC-US) in cervical cytology of post-menopausal women More immature cells then appear, and these naturally have larger centers relative to their size.18PubMed Central. Analysis of the related factors of atypical squamous cells of undetermined significance (ASC-US) in cervical cytology of post-menopausal women They can resemble atypical cells, which raises ASCUS rates in postmenopausal and older women.19PubMed Central. Analysis of the related factors of atypical squamous cells of undetermined significance (ASC-US) in cervical cytology of post-menopausal women A Pap and colposcopy are also harder to interpret after menopause, so HPV testing is the main guide.20PubMed Central. Management of ASC-US/HPV positive post-menopausal woman

A typical path is an HPV test on the same sample. If it’s negative, the likely cause is low estrogen rather than precancer, and a negative HPV test at this age is reassuring. If HPV is found, the usual next step is the same follow-up other women get, since menopause doesn’t remove the risk from the virus.

Some doctors prescribe a short course of vaginal estrogen before a repeat test, so the cells can be read in a healthier state. Atrophy also causes dryness and painful sex, which can be treated.

The same effect can appear after childbirth or on some medicines. Breastfeeding lowers estrogen for months, and some hormone-blocking treatments do the same. Mention these to your clinician, since they can affect the result.

When the Lab Itself Is the Cause

Deciding what counts as ASCUS is subjective and hard to repeat.21Journal of Clinical and Translational Pathology. Updates in Cervical Cancer Screening Guidelines, The Bethesda System for Reporting Cervical Cytology, and Clinical Management Recommendations When a second expert re-checked ASCUS slides, they agreed only 43% of the time, usually calling the rest milder.22JAMA. Interobserver Reproducibility of Cervical Cytologic and Histologic Interpretations: Realistic Estimates From the ASCUS-LSIL Triage Study Training with the official reference atlas didn’t improve agreement.23Cancer Cytopathology. Review of the Bethesda System atlas does not improve reproducibility or accuracy in the classification of atypical squamous cells of undetermined significance smears A sample might hold only a few borderline cells among thousands of normal ones, so what a reader sees depends on which cells they notice.

Labs also use the category as a safety net. They would rather flag a doubtful sample than miss a true change, since a missed precancer costs more than an extra follow-up test. The price is that some women get an ASCUS result that a second reader would call normal.

The testing method shifts the rate as well. Newer liquid-based Pap tests flag ASCUS more often, about 3% of tests versus 1.6% with the older method.24PubMed. Superior performance of liquid-based versus conventional cytology in a population-based cervical cancer screening program But the share with real changes was similar, which suggests the extra flags are not simply false alarms.25PubMed. Superior performance of liquid-based versus conventional cytology in a population-based cervical cancer screening program Liquid-based samples are preserved in fluid, which lets an HPV test run on the very same sample without calling you back. You usually can’t tell which method your lab used from the result, but the clinic can.

What Happens Next and Your Real Risk

For ages 25 to 65, the preferred step is an HPV test, often run automatically on the leftover sample (your report may call it a reflex HPV test).26Washington State Department of Health. PAP Smear/HPV Referral Guideline If it is negative for high-risk types, the chance of serious precancer is low, and the usual plan is routine screening again after a longer interval. If high-risk HPV is found, you’re usually referred for colposcopy, a closer look at the cervix with a magnifier and possibly a small biopsy.27PubMed Central. European guidelines for quality assurance in cervical cancer screening: recommendations for clinical management of abnormal cervical cytology, part 1. The combination of ASCUS and high-risk HPV raises the chance of a real change, so the test result, more than the ASCUS label, decides the path. A repeat Pap is an accepted alternative in some guidelines.28PubMed Central. European guidelines for quality assurance in cervical cancer screening: recommendations for clinical management of abnormal cervical cytology, part 1.

For ages 21 to 24, a repeat Pap in 12 months is usual.29Washington State Department of Health. PAP Smear/HPV Referral Guideline HPV infections are so common and so often temporary at this age that testing the virus would flag many women who don’t need further action. A year gives the immune system a chance to clear the infection first. If the repeat Pap shows persistent or worse changes, follow-up then moves toward colposcopy.

Colposcopy is done in the office and takes about 10 to 15 minutes. A vinegar solution highlights abnormal areas. A biopsy feels like a pinch or cramp, and light spotting afterward is normal.

About 10 to 20% of women with ASCUS are found to have a serious precancer (HSIL or CIN3) on biopsy.30Journal of Clinical and Translational Pathology. Updates in Cervical Cancer Screening Guidelines, The Bethesda System for Reporting Cervical Cytology, and Clinical Management Recommendations In one group with ASCUS or mild changes, about 9% developed a precancer needing treatment over follow-up.31PubMed Central. A cervical abnormalities risk prediction model: can we use clinical information to predict which patients with ASCUS/LSIL Pap tests will develop CIN2/3 or AIS? Most women with ASCUS never develop precancer.

Even when something is found, “abnormal” rarely means treatment right away. Many changes are mild and simply watched. Only serious precancer usually needs removal, which is quick and usually preserves fertility.

Newer tests can sharpen the sorting. A stain on the Pap sample, called p16/Ki-67 dual stain, finds about 92% of precancers in ASCUS cases.32PubMed. p16/ki-67 dual-stain cytology in the triage of ASCUS and LSIL papanicolaou cytology: results from the European equivocal or mildly abnormal Papanicolaou cytology study It also sends fewer women for colposcopy than HPV testing alone.33PubMed. p16/ki-67 dual-stain cytology in the triage of ASCUS and LSIL papanicolaou cytology: results from the European equivocal or mildly abnormal Papanicolaou cytology study

Coping With the Worry and What You Can Do

Many women with abnormal Pap results fear cancer and misunderstand the cause.34PubMed. Women’s knowledge and experience of atypical Pap results in a high risk community Many also say they weren’t given enough explanation.35PubMed. Women’s knowledge and experience of atypical Pap results in a high risk community Asking for your exact result and your next step usually eases worry.

Useful questions for your clinician: Was an HPV test done, and what was it? Was infection checked? When is my next test, and what kind? What result would change the plan?

The gap between a result and the next test is often the hardest part. Ask the clinic for a date and what you’ll be told afterward.

A few habits may help. Not smoking helps your body clear HPV, and HPV vaccination can still protect against types you haven’t caught, up to age 45 in some cases. Condoms lower but don’t eliminate spread. Avoid douching, which disturbs vaginal bacteria.

Timing matters for the next Pap too. Avoid sex, douching and vaginal products for two days before, reschedule if you have heavy bleeding, and treat any vaginal infection first if possible, so the sample doesn’t come back muddy.