Womens Health

Abnormal Pap Smear with Atypical Squamous Cell Changes

Frederick R. Jelovsek MD

"I have been having pap smears repeated every 3 months for about 9 months now per my gyn because of an abnormal smear. He said it's a category 2, not cancer but to keep an eye on this. Can this turn into a pre-cancer? He mentioned squamous cellular changes. What does all this mean? "

"Should I get a second opinion?" Becky D.

The Pap Smear is a screening test to pick up premalignant changes (dysplasia) in cervical cells so that treatment of those changes will prevent a future invasive cervical cancer. As with any screening test, the actual microscopic changes in the cervical tissue can be worse than the cells picked up on Pap indicate or they can be the same or even less abnormal. To tell what the actual changes are, you need a cervical biopsy in which the tissue is viewed under the microscope.

Doctors do not always recommend cervical biopsies for abnormal Pap smears because many of the abnormal Paps will regress to normal on their own. How the different classes of Pap abnormalities are followed depends upon many patient factors as well as how accurately the Pap smear is read by the cytologist or automated scanner.

One of the big difficulties in discussing Pap smears is the mixing and matching of different classification systems that have been used through out the years. The first system was a "Class" system and that was followed by a "dysplasia" system that was mostly based on the tissue biopsies rather than Pap changes. Then came a "CIN" classification and finally the currently used "Bethesda" system. As you can see from the table below, the current Bethesda system authors do not feel that distinguishing between moderate and severe dysplasia cellular changes can be very accurate by just looking at the Pap smear. On the other hand, they felt that atypical changes could be better classified as "favoring benign changes" or "favoring dysplasia changes".

Understanding a Pap Smear

Past Pap Smear Classification Systems
(Some pathologists may still use terms from these systems)

Class System Dysplasia System CIN System
Cervical intraepithelial neoplasia
Bethesda System
currently used classification
0 unsatisfactory unsatisfactory unsatisfactory
1 (or I) negative negative within normal limits
2 (or II) negative negative benign cellular changes
changes associated with infection, atrophy, repair (metaplasia), radiation
2 (or II) No term No term ASCUS or AGCUS favor benign
atypical squamous cell changes of undetermined significance favor benign
atypical glandular cell changes of undetermined significance
3 (or III) No term No term ASCUS or AGCUS favor dysplasia
atypical squamous cell changes of undetermined significance favor dysplasia
atypical glandular cell changes of undetermined significance favor dysplasia
3 or (III) mild I (or 1) LGSIL
low grade squamous intraepithelial dysplasia
No term moderate II (or 2) HGSIL
high grade squamous intraepithelial dysplasia
4 (or IV) severe III (or 3) HGSIL
high grade squamous intraepithelial dysplasia
4 (or IV) CIS
carcinoma in situ
III (or 3) HGSIL
high grade squamous intraepithelial dysplasia
4 (or V) carcinoma carcinoma carcinoma

The most recent proposed classification is is in the following table. It often takes years, however for pathologists and clinicians to make full transitions to the new terminology without including terminology from or referencing to past classification systems.

Bethesda 2001 Pap Smear Classification System

Bethesda 2001
currently used classification
Unsatisfactory for evaluation
   reason will be specified as to why it is unsatisfactory
Negative for intraepithelial lesion or malignancy
   vaginal organisms may be mentioned such as trichomonas, yeast, shift in vaginal flora, actinomyces, herpes simplex
   other non-neoplastic findings such as reactive changes associated with inflammation, radiation, or intrauterine device, glandular cells status post hysterectomy, or atrophy
   other changes such as endometrial cells in a woman over age 40
Epithelial cell abnormality
      Atypical squamous cells
         atypical squamous cell changes of undetermined significance ASC-US
         cannot exclude high grade intraepithelial lesion ASC-H
      LSIL - low-grade squamous intraepithelial dysplasia
         encompassing: HPV/mild dysplasia/CIN1
      HSIL - high-grade squamous intraepithelial dysplasia
         encompassing: moderate or severe dysplasia, CIS/CIN-2,CIN-3
         -with features suspicious for invasion (if invasion suspected)
      Squamous cell carcinoma

         - endocervical cells
         - endometrial cells
         - glandular cells
         - endocervical cells, favor neoplastic
         - glandular cells, favor neoplastic
      Endocervical adenocarcinoma in situ
         - endocervical
         - endometrial
         - extrauterine
         - not otherwise specified
Other malignant neoplasms/cancer

What does an abnormal Pap smear with atypical squamous cell changes mean?


When the cytologist or pathologist is looking at a Pap smear, they basically look for cells that have increased nuclear activity. If you remember your biology, the nucleus is larger in proportion to the cytoplasm in the cell than it normally is. This increased nuclear activity can be due to infection or cellular repair processes, irritation associated with atrophic changes of the low estrogen menopausal state, or external agents causing cell damage such as radiation therapy. Sometimes, however, the increased nuclear activity can indicate the cell is more rapidly dividing and thus replacing normal cells. This is called dysplasia and is considered premalignant change. If cellular changes associated with human papilloma virus are present, that may explain much of the increased nuclear activity.

If your Pap smear has atypical squamous changes, it should be read out as either ASCUS favor benign or ASCUS favor dysplasia. Most physicians do not currently recommend colposcopy and cervical biopsy for the category of ASCUS favor benign. In addition, for the category of ASCUS favor dysplasia, there are still many physicians who will just repeat the Pap smears at 3-4 month intervals as long as:

They do this because the yield of a biopsy to find a moderate or severe dysplasia is fairly low (5-10%) (1) and if those changes are actually present, it is likely that one of the subsequent Pap smears will pick up the more advanced dysplasia before there is any progression.

Atypical glandular cells of undetermined significance is a much different category. Make sure from the nurses or doctor's office that that is not what you have. If so, see our article, Atypical Glandular Cells of Unknown Significance (AGCUS).

Is this a precancerous condition?


In general, ASCUS (atypical squamous cells of undetermined significance) is not a precancerous change. It is a category that indicates some cellular irritation and one that bears repeating to see if there is any change toward dysplasia at a later time.

Dysplasia is considered a premalignant lesion but again it is important to note that dysplasia usually does not progress to invasive cancer of the cervix, but if it does, it usually takes 10 years or more. If you look at the table below about Pap smear progression from our article Natural Progression of an Abnormal Pap, keep in mind that if there are HPV changes associated with ASCUS, then progression may be greater.

Abnormal Pap Smear
Natural Progression and Regression

Abnormal Class Regression to Normal Progression to higher grade over 24 Months Progression to invasive cancer over 24 Months
ASCUS 68% 7% 0.25%
LGSIL 47% 21% 0.15%
HGSIL 35% 23% 1.44%

Is just following these and repeating the Pap smear all that needs to be done?


For the most part, yes. As you can see from the above table, even low grade squamous intraepithelial lesions (LGSIL) have a very low progression to cancer over the short run. With compliant patients in our office, we usually just repeat Pap smears about every 4 months for ASCUS favor benign, ASCUS favor dysplasia, and LGSIL. If any of the follow up Paps change to a HGSIL, or the LGSIL changes persist 3 or more times in a row, then colposcopy and cervical biopsy is performed to make sure there are not more severe or extensive changes. Many physicians will also followup ASCUS favor dysplasia similarly.

This approach works well for physicians and women favoring non intervention. Sometimes, however, women may have family histories of cervical cancer, fears of any cancer or just increased anxiety or even panic attacks about "something abnormal in my body". In that case, earlier biopsies and even treatment for mild cervical irritation may be the best way to minimize the anxiety that an abnormal Pap can evoke. You need to work with your doctor on this.

How can I get rid of these abnormal Pap smears?


Sometimes the frequent office visits for repeat Pap smears gets to be too emotionally aggravating. In that case, you may need to speak to your doctor about treating any cervical irritation that can be seen on colposcopic exam after it has been biopsied.

Any treatment that destroys the abnormal cells such as cryotherapy, laser, LEEP, electrical cautery or hyfercation (thermal heat cautery) will hopefully induce normal cells to heal over the destroyed area and result in a normal Pap smear after healing has taken place.

Does HPV virus cause these Pap abnormalities?


Human papilloma virus (HPV) is felt to play a major role in cervical dysplasia. In fact the ASCUS Pap smears that are present in woman with HPV are more likely to progress to a more severe grade of dysplasia. Most scientific investigators now believe that HPV either totally causes dysplasia and cervical cancer or it is a necessary cofactor along with some other cause.

One study of women who had LGSIL Pap smears had an 83% incidence of HPV DNA present in cervical samples when tested with a sensitive Hybrid Capture II (HCII)(R) assay. Another study of just ASCUS Pap smears found that repeat Pap smear was just as sensitive as HPV DNA testing (3) therefore at the current time, it does not appear that HPV testing in women with abnormal Pap smears will help separate those who are at risk for progression the the dysplasia versus those who are not.


Other Related Articles

HGSIL - High Grade Intraepithelial Lesions of the Cervix on Pap Smear
Natural Progression of an Abnormal Pap
Do You Need a Pap After a Hysterectomy?
Atypical Glandular Cells of Unknown Significance (AGCUS)
PAP Smear Diagnosis of Endometrial Cancer
PAP Smear Recommendations
Papillomavirus Testing of Abnormal Pap Smears

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