I ABNORMAL CERVICAL CYTOLOGY ^241 ^320 ^400 ^443

Approximately 50 million cervical cytologic tests are performed in the United States each year. Of these tests, the findings of 3-10% will be reported as atypical squamous cells of undetermined significance, and another 2-5% will show evidence of more severe abnormalities (see also the “Cancer Screening and Prevention” section in Part 3).

Test Result Reporting

Effective cervical cancer prevention requires recognition and treatment of the precursors of invasive cancer and includes standardized terminology to report cervical cytologic and histologic test results. The 2001 Bethesda System of cervical cytologic test result reporting generally is accepted in the United States and describes the categories of epithelial cell abnormalities, including atypical squamous cells, atypical glandular cells, and low-grade squamous intraepithelial lesions or high-grade squamous intraepithelial lesions (HSIL) (see Box 4-7). Histologic diagnoses of cervical abnormali­ties are reported as cervical intraepithelial neoplasia (CIN) grades 1-3. However, in 2012, concerns about the diagnostic and management limita­tions of the CIN 2 categorization for lower anogenital human papilloma­virus (HPV)-associated lesions led the College of American Pathologists and the American Society for Colposcopy and Cervical Pathology to adopt a unified histopathologic nomenclature with a single set of diagnostic terms for these lesions. The recommended terminology for HPV-associated squamous lesions of the lower anogenital tract is low-grade squamous intraepithelial lesions or HSIL, which may be further classified by the appli­cable -IN subcategorization. For example, cervical HSIL may be further qualified as (CIN 2) or (CIN 3). In addition, recommendations were made to describe the indications for the use of biomarkers to better define HPV- associated lesions of the lower anogenital tract and reduce interobserver variability in diagnosis.

Box 4-7. The 2001 Bethesda System for Reporting Cervical Cytology ^

Specimen Type

Indicate: conventional test (Pap test), liquid-based preparation, or other.

Specimen Adequacy

• Satisfactory for evaluation (describe presence/absence of endocervical/ transformation zone component and any other quality indicators, eg, partially obscuring blood, inflammation, etc.)

• Unsatisfactory for evaluation (specify reason)

— Specimen rejected/not processed (specify reason)

— Specimen processed and examined, but unsatisfactory for evaluation of epithelial abnormality because of (specify reason)

General Categorization (Optional)

• Negative for intraepithelial lesion or malignancy

• Other: see “Interpretation/Result” (eg, endometrial cells in a woman aged 40 years or older)

• Epithelial cell abnormality: See “Interpretation/Result” (specify “squa­mous” or “glandular” as appropriate)

Interpretation/Result

• Negative for intraepithelial lesion or malignancy (when there is no cellular evidence of neoplasia, state this in the “General Categorization” above, in the “Interpretation/Result” section of the report, or both, whether or not there are organisms or other nonneoplastic findings)

— Organisms

Trichomonas vaginalis

Fungal organisms morphologically consistent with Candida species Shift in flora suggestive of bacterial vaginosis

Bacteria morphologically consistent with Actinomyces species Cellular changes consistent with herpes simplex virus

(continued)

Box 4-7. The 2001 Bethesda System for Reporting Cervical Cytology (continued)

Interpretation/Result (continued)

— Other nonneoplastic findings (optional to report; list not inclusive) Reactive cellular changes associated with

Inflammation (includes typical repair)

Radiation

Intrauterine device

Glandular cells status posthysterectomy

Atrophy

• Other (list not comprehensive)

— Endometrial cells (in a woman aged 40 years or older) (specify if nega­tive for squamous intraepithelial lesion)

• Epithelial cell abnormalities

— Squamous cell

Atypical squamous cells (ASC)

Of undetermined significance (ASC-US)

Cannot exclude HSIL (ASC-H)

Low-grade squamous intraepithelial lesion (LSIL) (encompassing: human papillomavirus/mild dysplasia/cervical intraepithelial neoplasia (CIN) 1 High-grade squamous intraepithelial lesion (HSIL) (encompassing: moderate and severe dysplasia, carcinoma in situ; CIN 2 and CIN 3) With features suspicious for invasion (if invasion is suspected) Squamous cell carcinoma

— Glandular cell

Atypical

Endocervical cells (not otherwise specified or specify in comments) Endometrial cells (not otherwise specified or specify in comments) Glandular cells (not otherwise specified or specify in comments) (continued)

Box 4-7.

Interpretation/Result (continued)

• Epithelial cell abnormalities (continued)

Atypical

Endocervical cells, favor neoplastic

Glandular cells, favor neoplastic

Endocervical adenocarcinoma in situ (AIS)

Adenocarcinoma

Endocervical

Endometrial

Extrauterine

Not otherwise specified

• Other malignant neoplasms (specify)

Ancillary Testing

Provide a brief description of the test method(s) and report the result so that it is easily understood by the clinician.

Automated Review

If case examined by automated device, specify device and result.

Educational Notes and Suggestions (Optional)

Suggestions should be concise and consistent with clinical follow-up guidelines published by professional organizations (references to relevant publications may be included).

Reprinted from Solomon D, Nayar R, editors. The Bethesda system for reporting cervical cytology : Definitions, criteria, and explanatory notes. 2nd ed. New York (NY): Springer; 2004, with kind permission of Springer Science+Media.

Evaluation and Management of Screening Results

Visual inspection of the vagina and cervix and a bimanual examination should follow a cytology report of abnormal findings. The first objective is to exclude the presence of invasive carcinoma. Once this has been accom­plished, the objectives are to determine the grade and distribution of the intraepithelial lesion. Options for evaluation include repeat cytology, HPV DNA testing, colposcopy with directed biopsies, and endocervical assess­ment (see Table 4-3).

The expertise required to evaluate and manage patients with abnormal cytologic findings includes a thorough knowledge of the significance and natural history of cervical preinvasive disease. Additionally, the person responsible for evaluating the abnormal test result should be appropriately trained and experienced in colposcopy and aware of the various treatment options available for managing cervicovaginal abnormalities. Access to an appropriate cytologic and histopathologic laboratory is required.

• Colposcope

• Acetic acid solution, 3-5%

• Hemostatic solution, such as Monsel’s solution

• Instruments for the following:

— Cervical biopsy

— Endocervical sampling

• Appropriate fixative solution

The Clinical Laboratory Improvement Amendments have established requirements for the review of abnormal cervical cytology and follow-up of tests of identified high-risk patients (see also the “Compliance With Government Regulations” in Part 1, and Appendix E). In addition, clini­cians should be familiar with any state requirements in this area.

In 2012, the American Society for Colposcopy and Cervical Pathology convened a consensus conference to update its recommendations on the appropriate management of women with cervical cytologic or histologic abnormalities (see Bibliography). These guidelines define when to return

Table 4-3. Management of Cervical Cancer Screening Results

Abbreviations: ASC-US, atypical squamous cells of undetermined significance; ASCCP, American Society for Colposcopy and Cervical Pathology; HPV, human papillomavirus.

* Massad LS, Einstein MH, Huh WK, Katki HA, Kinney WK, Schiffman M, et al. 2012 updated con­sensus guidelines for the management of abnormal cervical cancer screening tests and cancer precursors. 2012 ASCCP Consensus Guidelines Conference; Obstet Gynecol 2013;121:829-46.

Modified with permission from Saslow D, Solomon D, Lawson HW, Killackey M, Kulasingam SL, Cain J, et al. American Cancer Society, American Society for Colposcopy and Cervical Pathology, and American Society for Clinical Pathology screening guidelines for the preven­tion and early detection of cervical cancer. ACS-ASCCP-ASCP Cervical Cancer Guideline Committee. CA Cancer J Clin 2012;62:147-72.

to routine screening after treatment or resolution of abnormalities, given longer screening intervals than in the past; explain how to incorporate HPV testing; apply guidelines previously developed for adolescents to women aged 21-24 years; and integrate new data on risk of high-grade precur­sor lesions and cancer. A summary of these guidelines, including practice algorithms, is provided in the American College of Obstetricians and Gynecologists’ Practice Bulletin No. 140 (see Bibliography).

Bibliography

Darragh TM, Colgan TJ, Cox JT, Heller DS, Henry MR, Luff RD, et al. The Lower Anogenital Squamous Terminology Standardization Project for HPV-Associated Lesions: background and consensus recommendations from the College of American Pathologists and the American Society for Colposcopy and Cervical Pathology. Members of LAST Project Work Groups [published erratum appears in J Low Genit Tract Dis 2013;17:368]. J Low Genit Tract Dis 2012;16:205-42. [PubMed] [Full Text]

Management of abnormal cervical cancer screening test results and cervical cancer precursors. Practice Bulletin No. 140. American College of Obstetricians and Gynecologists. Obstet Gynecol 2013;122: 1338-67. [PubMed] [Obstetrics & Gynecology]

Massad LS, Einstein MH, Huh WK, Katki HA, Kinney WK, Schiffman M, et al. 2012 updated consensus guidelines for the management of abnormal cervical cancer screening tests and cancer precursors.

Schiffman M, Wentzensen N. From human papillomavirus to cervical cancer. Obstet Gynecol 2010;116:177-85. [PubMed] [Obstetrics & Gynecology]

Screening for cervical cancer. Practice Bulletin No. 131. American College of Obstetricians and Gynecologists. Obstet Gynecol 2012;120:1222-38. [PubMed] [Obstetrics & Gynecology]

Solomon D, Nayar R, editors. The Bethesda system for reporting cervical cytology : Definitions, criteria, and explanatory notes. 2nd ed. New York (NY): Springer; 2004.

Resources

American College of Obstetricians and Gynecologists. Cervical cancer screen­ing. Patient Education Pamphlet AP085. Washington, DC: American College of Obstetricians and Gynecologists; 2013.

American College of Obstetricians and Gynecologists. Colposcopy. Patient Education Pamphlet AP135. Washington, DC: American College of Obstetricians and Gynecologists; 2013.

American College of Obstetricians and Gynecologists. Understanding abnormal pap test results. ACOG Patient Education Pamphlet AP161. Washington, DC: American College of Obstetricians and Gynecologists; 2009.

American Society for Colposcopy and Cervical Pathology. Available at: http://www. asccp.org. Retrieved September 18, 2013.