Management of atypical squamous cells (ASC-US and ASC-H) and low grade cervical squamous intraepithelial lesions (LSIL)

Management of atypical squamous cells (ASC-US and ASC-H) and low grade cervical squamous intraepithelial lesions (LSIL)

Authors
Annekathryn Goodman, MD
Christine H Holschneider, MD
Section Editor
Barbara Goff, MD
Deputy Editor
Sandy J Falk, MD

Disclosures

INTRODUCTION — Squamous cells make up the outer layer of the cervix and vagina . Atypical squamous cells (ASC) is the name given to squamous cells on a Pap smear or cervical cytology that do not have a normal appearance but are not clearly precancerous. Low grade squamous intraepithelial lesions (LSIL, also called low grade cervical intraepithelial neoplasia) refers to cells that appear slightly abnormal.

Women who have ASC or LSIL require further testing because some women with these findings have a precancerous lesion of the cervix.

This topic review discusses the management of women with ASC and LSIL. The management of women with high grade squamous intraepithelial lesions (HSIL) and atypical glandular cells (AGC) are discussed in a separate topic review. (See “Patient information: Management of high grade cervical squamous intraepithelial lesions (HSIL) and glandular abnormalities (AGC)”.)

ATYPICAL SQUAMOUS CELLS (ASC) — ASC is subdivided into atypical squamous cells of undetermined significance (ASC-US) and atypical squamous cells, cannot rule out a high grade lesion (ASC-H). The risk of a high-grade precancerous lesion in women with ASC-US is 15 percent and for those with ASC-H, the risk is 38 percent [1].

Atypical squamous cells of undetermined significance (ASC-US) — In women older than 20 years, there are three options for evaluation of a single ASC-US result. Women who are pregnant or younger than age 20 years are evaluated differently (see ‘Adolescents’ below and ‘Pregnant women’ below).

Perform HPV testing. This is the preferred follow up for ASC-US. HPV testing is often done at the same time as the Pap smear. This is convenient because a woman does not have to return for a second visit. HPV testing is described in detail in a separate topic review (see “Patient information: Cervical cancer screening”).

Women who test positive for HPV types that are high risk for cervical cancer should have colposcopy because they are at greater risk of having an underlying precancerous lesion.

Women who test negative for HPV are not likely to have cervical precancer. These women should have a repeat Pap smear in one year. In most cases, the ASC-US resolves during this time.
Repeat the Pap smear in six months. If this test is normal, it is repeated once more after another six months until there have been two normal tests in a row; the woman can then return to routine screening. If the woman has a second ASC-US result or a more severe abnormality develops, colposcopy is recommended. (See ‘Colposcopy’ below.)
Have colposcopy. (See ‘Colposcopy’ below.)
Atypical squamous cells, cannot rule out a high grade lesion (ASC-H) — ASC-H is more likely than ASC-US to be caused by a precancerous change. This finding requires further evaluation with colposcopy (see ‘Colposcopy’ below).

LOW-GRADE SQUAMOUS LESION (LSIL) — LSIL is usually caused by mild cellular changes. Further testing with colposcopy and cervical biopsy is almost always recommended for women with LSIL because 12 to 16 percent of women with LSIL have a precancerous lesion [2,3].

However, adolescents and postmenopausal women are evaluated somewhat differently (see ‘Adolescents’ below and ‘Postmenopausal women’ below). Pregnant women are evaluated similarly to non-pregnant women but are also discussed separately below.

The management of women with LSIL depends upon what is seen with colposcopy and biopsy (see ‘Management after colposcopy’ below); most clinicians will delay biopsy until after delivery in pregnant women (see ‘Pregnant women’ below).

COLPOSCOPY — Colposcopy is an office procedure that allows a clinician to closely examine the cervix. It is commonly performed after an abnormal Pap smear. Colposcopy is performed similar to a pelvic examination, while the woman lies on an exam table. A speculum is used to view the cervix, and the viewing device (called a colposcope) remains outside the woman’s body (picture 1).

The colposcope magnifies the appearance of the cervix. This allows the clinician to better see the location and size of any abnormalities, and also to see any changes in the capillaries (small blood vessels) on the surface of the cervix.

During colposcopy, a small piece of the abnormal area can be removed (biopsied). Anesthesia (numbing medicine) is not needed because the biopsy causes only mild discomfort or cramping.

Some women also need to have a biopsy of the inner cervix during colposcopy; this is called endocervical curettage (ECC). Endocervix refers to the inner cervix and curettage means scraping. Pregnant women should not have ECC because it may disturb the pregnancy.

Management after colposcopy — Most women who have colposcopy have a biopsy of any abnormal-appearing areas. The biopsy samples are sent to a pathologist, who determines if there is any evidence of precancerous changes, termed cervical intraepithelial neoplasia (CIN). These changes are categorized as being mild (CIN 1) or moderate to severe (CIN 2 or 3).

CIN 1 biopsy in women with Pap smear results that were ASC-US, ASC-H or LSIL cytology – Follow-up is recommended with either HPV testing at 12 months or a Pap smear at six and 12 months. The reason for this recommendation is that CIN I is a minor abnormality that usually goes away over time without treatment. Waiting and repeating testing allows time for the abnormality to resolve, and also enables the healthcare provider to identify the few situations in which the abnormality has become more severe. Repeat colposcopy is recommended if the results of the follow-up Pap smear are ASC or greater or if the HPV test is positive. Women with two consecutive negative repeat cytology results or a negative HPV test can resume routine screening.
CIN biopsy in women with Pap smear results that were high-grade SIL (HSIL) or atypical glandular cells-not otherwise specified – Follow-up can be one of three options: (1) Pap smear and colposcopy every six months for a year; (2) re-review of both Pap smear and biopsy results by a pathologist; or (3) a procedure to remove a larger piece of tissue from the cervix (cone biopsy or loop electrosurgical excision procedure [called LEEP, loop, or LLETZ]).
CIN 2 or 3 — CIN 2 or 3 is usually treated by removing or destroying the abnormal area (using a cone biopsy, LEEP, laser, or freezing procedure). The reason for this recommendation is that moderate to severe precancerous abnormalities (CIN 2 or 3) are unlikely to resolve over time without treatment, and may progress to cancer if left untreated over a period of years. (See “Patient information: Treatment of precancerous cells of the cervix”.) However, adolescents and pregnant women are often able to delay treatment (see ‘Adolescents’ below and ‘Pregnant women’ below).
SPECIAL CIRCUMSTANCES

Postmenopausal women — In postmenopausal women, LSIL may be evaluated differently because thinning and drying of the tissues (referred to as atrophy) can cause the cells to appear abnormal. These changes often resolve with time and are often not related to changes caused by HPV. Options for postmenopausal women with LSIL include the following:

Colposcopy
HPV testing
Repeat Pap smear at six and 12 months
If the HPV testing or repeat Pap smear tests are negative, the woman may return to routine testing. If the HPV test or repeat Pap smear are abnormal (ASC or greater), colposcopy is recommended.

The management of postmenopausal women after colposcopy is discussed above (see ‘Management after colposcopy’ above).

Adolescents — In adolescent women (age 20 years or younger), abnormal Pap smear is often approached differently because, in this age group, there is a good chance that the abnormal area will resolve over time, without treatment. There is a high rate of HPV infection in this group, but a very low rate of cervical cancer.

ASC-US, LSIL, and/or CIN 1 — Adolescents with ASC-US, LSIL, and/or CIN 1 are often advised to have repeat Pap smear in 12 months. HPV testing is not recommended because it is likely to be positive and would not affect the recommendation to repeat the test in 12 months.

If the 12 month cytology shows ASC-US, ASC-H, or LSIL, the test is usually repeated 12 months later (at 24 months).
If the 12 month cytology shows HSIL or worse, the adolescent is usually advised to have colposcopy (see ‘Colposcopy’ above).
If the 24 month test is abnormal (ASC-US or greater), the adolescent is usually advised to have colposcopy. If the 24 month test is normal, Pap smear is recommended once yearly.

High grade lesions (CIN 2 or 3) — Adolescents with HSIL should undergo colposcopy. If cervical biopsy does NOT show HSIL, they can be followed with colposcopy and Pap smear every six months for two years. If cervical biopsy confirms HSIL, they can either be followed with Pap smear and colposcopy or HPV testing until they have had normal testing for one year. If these follow-up results are normal, they can resume routine screening. If follow-up testing shows abnormalities or the cervix cannot be fully evaluated, they will need further testing or removal of a part of the cervix (cone biopsy or LEEP). (See “Patient information: Treatment of precancerous cells of the cervix”.)

Pregnant women — The evaluation and management of pregnant women is different from non-pregnant women because of the risk that trauma to the cervix could lead to preterm labor or delivery.

ASC-US — Pregnant women with ASC-US and a positive HPV test may elect to have colposcopy during pregnancy or wait until at least six weeks after delivering their baby. The reason for this recommendation is that cervix appears somewhat different during pregnancy, which can make it difficult to determine if an area appears abnormal due to pregnancy or due to precancerous changes. In addition, most mild abnormalities resolve over time without treatment.
ASC-H — Pregnant women with ASC-H should have a colposcopy. This is because ASC-H is more likely than ASC-US to be caused by a precancerous change.
LSIL — Colposcopy is recommended for pregnant women with LSIL, similar to non-pregnant women.
WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem.

 

Related topics for patients, as well as selected articles written for healthcare professionals, are also available. Some of the most relevant are listed below.

Patient Level Information:

Patient information: Management of high grade cervical squamous intraepithelial lesions (HSIL) and glandular abnormalities (AGC)
Patient information: Cervical cancer screening
Patient information: Treatment of precancerous cells of the cervix

Professional Level Information:

Cervical adenocarcinoma in situ
Cervical cancer in pregnancy
Cervical cancer screening tests: Techniques and test characteristics of cervical cytology and human papillomavirus testing
Cervical cytology: Evaluation of atypical and malignant glandular cells
Cervical cytology: Evaluation of atypical squamous cells (ASC-US and ASC-H)
Cervical cytology: Evaluation of high grade squamous intraepithelial lesions
Cervical cytology: Evaluation of low grade squamous intraepithelial lesions
Cervical intraepithelial neoplasia: Definition, incidence, and pathogenesis
Cervical intraepithelial neoplasia: Management
Preinvasive and invasive cervical neoplasia in HIV-infected women
Screening for cervical cancer

The following organizations also provide reliable health information [2,4,5].

National Library of Medicine
(www.nlm.nih.gov/medlineplus/healthtopics.html)

American Society for Colposcopy and Cervical Pathology
(www.asccp.org)

Center for Disease Control and Prevention
(www.cdc.gov/)

American Social Health Association
(file://www.ashastd.org/)

REFERENCES
Castle PE, Fetterman B, Thomas Cox J, et al. The age-specific relationships of abnormal cytology and human papillomavirus DNA results to the risk of cervical precancer and cancer. Obstet Gynecol 2010; 116:76.
Wright TC Jr, Massad LS, Dunton CJ, et al. 2006 consensus guidelines for the management of women with abnormal cervical cancer screening tests. Am J Obstet Gynecol 2007; 197:346.
Cox JT, Schiffman M, Solomon D, ASCUS-LSIL Triage Study (ALTS) Group. Prospective follow-up suggests similar risk of subsequent cervical intraepithelial neoplasia grade 2 or 3 among women with cervical intraepithelial neoplasia grade 1 or negative colposcopy and directed biopsy. Am J Obstet Gynecol 2003; 188:1406.
Safaeian M, Solomon D, Wacholder S, et al. Risk of precancer and follow-up management strategies for women with human papillomavirus-negative atypical squamous cells of undetermined significance. Obstet Gynecol 2007; 109:1325.
Wright TC Jr, Massad LS, Dunton CJ, et al. 2006 consensus guidelines for the management of women with cervical intraepithelial neoplasia or adenocarcinoma in situ. Am J Obstet Gynecol 2007; 197:340.