Abnormal Pap Test Result: Low-Grade Squamous Intraepithelial Lesion and High-Grade Squamous Intraepithelial Lesion

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Chapter 98 Abnormal Pap Test Result: Low-Grade Squamous Intraepithelial Lesion and High-Grade Squamous Intraepithelial Lesion

INTRODUCTION

Description: Low-grade squamous intraepithelial lesions (LGSIL) encompass changes associated with human papillomavirus (HPV), mild dysplasia, and cervical intraepithelial neoplasia (CIN) I. High-grade squamous intraepithelial lesions (HGSIL) include CIN II and III and carcinoma in situ (CIS).
Prevalence: Less than 5% of Pap tests for low-grade and 2% for high-grade abnormalities.
Predominant Age: Reproductive.
Genetics: No genetic pattern.

ETIOLOGY AND PATHOGENESIS

Causes: HPV appears to be responsible for the development of cervical dysplasia. Although as many as 70% of invasive cervical cancers have HPV serotypes 16 or 18 present, these types may be detected in patients with LGSIL as well. Normal patients have HPV prevalence rates that vary from 10% to 50%, depending on the study technique and population evaluated.
Risk Factors: Exposure to HPV and other sexually transmitted disease; smoking is associated with a higher risk.

CLINICAL CHARACTERISTICS

Signs and Symptoms

• Asymptomatic

DIAGNOSTIC APPROACH

Differential Diagnosis

• LGSIL—inflammatory change (cervicitis)
• Cervical carcinoma
• HGSIL—cervical CIS
• Invasive cervical carcinoma

Associated Conditions: HPV infection, vaginitis, cervicitis, cervical dysplasia, carcinoma in situ, invasive carcinoma of the cervix, endocervical adenocarcinoma.

Workup and Evaluation

Laboratory: No evaluation indicated.
Imaging: No imaging indicated.
Special Tests: High prevalence, a poor correlation with later risk, and the cost of screening have resulted in the general recommendation that routine HPV screening or serotyping not be carried out.
Diagnostic Procedures: For many patients with LGSIL, colposcopy, colposcopically directed biopsy, and endocervical curettage are appropriate to establish the source of the cytologic abnormality. (For compliant adolescents, a repeat Pap test in 6 and 12 months or high-risk HPV test alone in 12 months are acceptable alternatives.) If colposcopy is inadequate to delineate lesions present or the entire transformation zone cannot be seen, diagnostic conization may be needed. Colposcopy, colposcopically directed biopsy, and endocervical curettage should be used to evaluate all patients with HGSIL.

Pathologic Findings

Acetowhite areas on colposcopy, early vascular changes leading to mosaicism and punctation. Microscopic—loss of normal maturation, increased nuclear/cytoplasmic ratio, nuclear atypia (mild). Vascular changes leading to mosaicism and punctation (severe) are more typical of HGSIL. Nuclear atypia (moderate to severe) is also a feature of HGSIL.

MANAGEMENT AND THERAPY

Nonpharmacologic

General Measures: Evaluation of comments made by the cytopathologist. Increased frequency of Pap tests until the abnormality is resolved or further diagnosis is established. (For a follow-up Pap test to be “negative,” it must have normal or benign findings, but it also must be “satisfactory for interpretation.”)
Specific Measures: Compliant patients with LGSIL who are at low risk for HPV, sexually transmitted disease, and malignant progression of the lesion (e.g., smokers) may be followed by serial Pap tests. If colposcopy is adequate and the histologic abnormality found is mild, obtaining follow-up Pap tests at 4- to 6-month intervals for 2 years or three normal tests is suitable. When HGSIL is present, the evaluation determines therapy: cryotherapy, electrocautery, electrosurgical loop excision, laser ablation, or conization. Treatment must be based on an accurate diagnosis and the extent of the lesion involved. (Treatment of CIN 1 in women younger than age 21 is not recommended, even if the lesion persists. Virtually all are manifestations of a transient HPV infection and will resolve, although complete resolution may take up to 36 months.)
Diet: No specific dietary changes indicated.
Activity: No restriction.
Patient Education: Reassurance; American College of Obstetricians and Gynecologists Patient Education Pamphlet AP085 (The Pap Test), AP073 (Human Papillomavirus Infection).

Drug(s) of Choice

Based on specific indications, most therapy is surgical or ablative in nature.

FOLLOW-UP

Patient Monitoring: Normal health maintenance, increased frequency of Pap tests.
Prevention/Avoidance: Avoidance of HPV infection.

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Possible Complications: Progression to more severe squamous abnormalities. (Data suggest that for adolescents, virtually all atypical squamous cells of undetermined significance [ASCUS] and low-grade HPV-mediated changes are transitory and that regression to normal is to be expected without intervention.)
Expected Outcome: Of patients with these findings, 60% or more undergo spontaneous regression of the underlying process, resulting in a return to normal Pap test results. Only 15% of patients with LGSIL progress to HGSIL. HGSIL abnormalities are more likely to progress and warrant more aggressive evaluation and treatment.

MISCELLANEOUS

Pregnancy Considerations: No effect on pregnancy. Because of the potential significance of the HGSIL abnormality and the pathologic conditions that cause it, a delay in pregnancy while evaluation is ongoing may be advisable.
ICD-9-CM Codes: 622.1 (LGSIL), 233.1 (HGSIL, includes carcinoma in situ).

REFERENCES

Level I

Brewster WR, Hubbell FA, Largent J, et al. Feasibility of management of high-grade cervical lesions in a single visit: a randomized controlled trial. JAMA. 2005;294:2182.

Level II

Dehn D, Torkko KC, Shroyer KR. Human papillomavirus testing and molecular markers of cervical dysplasia and carcinoma. Cancer. 2007;111:1.

Higgins RV, Hall JB, McGee JA, et al. Appraisal of the modalities used to evaluate an initial abnormal Papanicolaou smear. Obstet Gynecol. 1994;84:174.

Nasiell K, Roger V, Nasiell M. Behavior of mild cervical dysplasia during long-term follow-up. Obstet Gynecol. 1986;67:665.

Level III

American College of Obstetricians and Gynecologists. Cervical cytology screening. ACOG Practice Bulletin 45. Obstet Gynecol. 2003;102:417.

American College of Obstetricians and Gynecologists. Cervical cancer screening in adolescents. ACOG Committee Opinion 300. Obstet Gynecol. 2004;104:885.

American College of Obstetricians and Gynecologists. Management of abnormal cervical cytology and histology. ACOG Practice Bulletin 66. Obstet Gynecol. 2005;106:645.

American College of Obstetricians and Gynecologists. Evaluation and management of abnormal cervical cytology and histology in the adolescent. ACOG Committee Opinion 330. Obstet Gynecol. 2006;107:963.

Apgar BS, Zoschnick L, Wright TCJr. The 2001 Bethesda System terminology. Am Fam Physician. 2003;68:1992.

Brinton LA, Hamman RF, Huggins GR, et al. Sexual and reproductive risk factors for invasive squamous cell cervical cancer. J Natl Cancer Inst. 1987;79:23.

Carmichael JA, Maskens PD. Cervical intraepithelial neoplasia: examination, treatment and follow-up: review. Obstet Gynecol Surg. 1985;40:545.

Dehn D, Torkko KC, Shroyer KR. Human papillomavirus testing and molecular markers of cervical dysplasia and carcinoma. Cancer. 2007;111:1.

Klinkhamer PJ, Meerding WJ, Rosier PF, Hanselaar AG. Liquid-based cervical cytology. Cancer. 2003;99:263.

Noller KL. Intraepithelial neoplasia of the lower genital tract (cervix, vulva). In: Katz VL, Lentz GM, Lobo RA, Gershenson DM, editors. Comprehensive Gynecology. 5th ed. Philadelphia: Mosby/Elsevier; 2007:752.

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