The minimally abnormal Pap smear: a conservative approach - Editorial

Author: Thomas J. Zuber
Date: March, 1996

The incidence of cervical cancer in the United States declined sharply in the four decades following the introduction of the Papanicolaou (Pap) smear in 1941.[1,2] The use of Pap testing has reduced cervical cancer mortality by over 70 percent,[1] but too many women still die of the disease. A high false-negative rate of between 20 percent and 40 percent was believed to be a major cause for the failure of early detection of cancer by Pap something.[1,3]

To improve detection of cervical cancer, ancillary screening and detection methods were developed. Directed biopsy, following magnified examination of the stained cervix (colposcopy), became a widely accepted means of evaluating abnormal Pap smears and detecting precancerous dysplastic lesions. As the rates of cervical intraepithehal neoplasia (CIN) and human papillomavirus. (HPV) infection escalated in the United States in the 1970s and 1980s, extensive efforts were initiated to train primary care physicians in the detection and treatment of CIN.

Our understanding of the relationship between CIN and cervical cancer has also evolved. The Pap classification system that had been used for many years was in recent years supplanted by the Bethesda classification system.[4] Older treatment guidelines that recommended treatment of any form of cervical dysplasia were replaced with less aggressive approaches.[1-3,5-7] More conservative management of mild abnormalities was proposed, since only 1 percent of the lowest-grade cervical lesions develop into cancer and the process generally takes many years.[1] The recommendation for nonsurgical management of the minimally abnormal Pap smear includes the abnormalities of atypia, HPV-related changes and even mild dysplasia.

The Bethesda system describes atypical squamous cells of undetermined significance (ASCUS) as a squamous cell abnormality that requires further qualification.[4,5] The cytopathologist should communicate to the clinician if a reactive or premalignant process is favored.[2,4,5] Less than 5 percent of Pap smears should be described as ASCUS[2,5] but in certain communities up to 30 percent of the Pap smears are interpreted as unqualified ASCUS. Since up to 75 percent of unqualified ASCUS smears have associated normal histology, a repeat Pap smear is recommended for these patients in four to six months.[2,5] Colposcopy should be performed only in patients with ASCUS smears suspicious for high-grade dysplasia or malignancy or those demonstrating persistent ASCUS on repeat testing. Colposcopic examination following the first unqualified ASCUS smear appears unnecessarily expensive and emotionally traumatic to the patient.[3]

The Bethesda system categorizes low-grade squamous intraepithelial lesions (LSIL) as cellular changes associated with HPV or mild dysplasia (CIN grade 1).[4] High-grade squamous intraepithelial lesions (HSIL) include moderate and severe dysplasia (CIN grade 2 and 3).[4] Long-term studies demonstrate that HPV-associated lesions and mild dysplasia progress to HSIL at similar rates.[5]

The classification of CIN 1 is further complicated by the inability of pathologists to clearly differentiate HPV-associated lesions (koilocytosis) from CIN 1.[5,8] Studies have shown a lack of inter- and intraobserver reproducibility in differentiating low-grade lesions.[5,8] Differentiating treatment recommendations between atypia and CIN 1 is problematic, and it has been suggested that CIN 1 represents more of a tissue response to HPV than a true premalignant change.[9]

Most cytology (Pap) specimens demonstrating LSIL represent processes that will spontaneously revert to normal without therapy.[2,5,7] Some experts[2,5] recommend that patients with LSIL on cytology can be managed with repeated cervical smears in four to six months, with colposcopic evaluation reserved for those with persistent abnormalities.

Some physicians perform colposcopy after the initial LSIL smear because of the possibility of underreporting of cervical cytology.[5] Others believe that biopsy of the cervix is necessary for definitive evaluation of dysplasia, but high rates of resolution of CIN 1 have been noted for both cytologically proven disease (by means of Pap smear) and histologically proven disease (by means of biopsy). Colposcopy after a single LSIL smear, however, may be appropriate for high-risk or unreliable patients. Persistent changes should prompt intervention, because of the increased risk of high-grade disease.

Following histologic (colposcopic biopsy) confirmation of a low-grade lesion and if the entire cervical lesion is visualized and the limits of the transformation zone are seen at colposcopy, an LSIL lesion can be monitored without treatment.[5]

Approximately 60 percent to 70 percent of biopsy-confirmed LSIL lesions regress spontaneously.[2,5-7,10] Because the relative immunodeficiency of pregnancy often allows for the development or progression of dysplastic changes, pregnant patients with LSIL should be monitored throughout the pregnancy. Definitive therapy should be delayed, when possible, until after delivery and reserved for those with persistent abnormalities.[5,11]

Biopsy of the cervix and subsequent reparative changes may produce local inflammation that can hasten the resolution of cervical dysplasia. The body's immune system often requires more than one to three months to respond to cellular injury or infection of the cervix.[12] Longer intervals (four to six months) seem appropriate for follow-up of low-grade cytologic changes of the cervix.[2,5] Mild cytologic changes may be noted for up to two to three years before resolving. HSIL discovered during the follow-up period, however, should prompt treatment.

Nutritional factors appear to influence the resolution of cervical dysplasia. Supplements with folate, beta carotene, and vitamins A, C and E may promote resolution of dysplasia.[13-15] Women followed in our practice for cervical dysplasia are encouraged to take a multivitamin with folate and antioxidants. We also strongly support the National Institutes of Health recommendation that all American eat at least five servings of fresh fruits and vegetables daily.

Cervical cancer clearly is a smoking-related disease.[16] The natural history of premalignant cervical disease is influenced by cigarette smoking, and smoking may promote the redevelopment of disease following treatment. Factors in cigarette smoke interfere with the immune system response[14,16] and may promote the growth of HPV. All women with a history of cervical dysplasia should be counseled to discontinue smoking.

Each evaluation and treatment of an abnormal Pap smear is estimated to cost $1,000 in the United States. All told, this $5.5-billion price tag[2] has created an undue economic burden on our health care system. The narrower indications for colposcopy and the more conservative management of low-grade lesions would reduce costs without exposing women to excessive risk.

Evaluation of cytologic abnormalities identified on screening Pap smears also represents a substantial burden on the health care resources of this country.[6] Aggressive intervention and overtreatment of mild cervical disease produces significant psychologic and physical morbidity for women.[6] Cautious observation of low-grade changes in women with minor Pap smear abnormalities is both appropriate and fiscally responsible.

REFERENCES

[1.] Larsen NS. Invasive cervical cancer rising in young white females. J Natl Cancer Inst 1994;86:6-7. [2.] Kurman RJ, Henson DE, Herbst AL, Noller KL, Schiffman MH. Interim guidelines for management of abnormal cervical cytology. JAMA 1994;271: 1866-9. [3.] Sedlacek T. Clinical options on dealing with minor cytologic abnormalities. Colposcopist 1992;24(4):1-2. [4.] The revised Bethesda system for reporting cervical/vaginal cytologic diagnoses: report of the 1991 Bethesda workshop. J Reprod Med 1992;37:383-6. [5.] American College of Obstetricians and Gynecologists. Cervical cytology: evaluation and management of abnormalities. ACOG technical bulletin no. 183. Washington, D.C.: ACOG, 1993:1-8. [6.] Montz FJ, Monk BJ, Fowler JM, Nguyen L. Natural history of the minimally abnormal Papanicolaou smear. Obstet Gynecol 1992;80(3 Pt 1):385-8. [7.] Kirby AJ, Spiegelhalter DJ, Day NE, Fenton L, Swanson K, Mann EM, et al. Conservative treatment of mild/moderate cervical dyskaryosis: long-term outcome. Lancet 1992;339:828-31. [8.] Ismail SM, Colclough AB, Dinnen JS, Eakins D, Evans DM, Gradwell E, et al. Observer variation in histopathological diagnosis and grading of cervical intraepithelial neoplasia. BMJ 1989;298:707-10. [9.] Kiviat NB, Koutsky LA. Specific human papillomavirus types as the causal agents of most cervical intraepithehal neoplasia: implications for current views and treatment [Editorial]. J Natl Cancer Inst 1993;85:934-5. [10.] Nasiell K, Roger V, Nasiell M. Behavior of mild cervical dysplasia during long-term follow-up. Obstet Gynecol 1986;67:665-9. [11.] Patsner B. Management of low-grade cervical dysplasia during pregnancy. South Med J 1990;83:1405-6, 1412. [12.] Reiter RC. Management of initial atypical cervical cytology: a randomized, prospective study Obstet Gynecol 1986;68:237-40. [13.] Butterworth CE Jr, Hatch KD, Gore H, Mueller H, Krumdieck CL. Improvement in cervical dysplasia associated with folic acid therapy in users of oral contraceptives. Am J Clin Nutr 1982;35:73-82. [14.] Palan PR, Mikhail MS, Basu J, Romney SL. Plasma levels of antioxidant beta-carotene and alpha-tocopherol in uterine cervix dysplasias and cancer. Nutr Cancer 1991;15:13-20. [15.] Romney SL, Palan PR, Duttagupta C, Wassertheil-Smoller S, Wylie J, Miller G, et al. Retinoids and the prevention of cervical dysplasias. Am J Obstet Gynecol 1981;141:890-4. [16.] Winkelstein W Jr. Smoking and cervical cancer-current status: a review. Am J Epidemiol 1990;131:945-57.

Dr. Zuber is an assistant clinical professor of family medicine at Michigan State University, Lansing. He is a member of the American Society of Colposcopy and Cervical Pathology and a recognized educator in colposcopy and LEEP.

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