What is the purpose and application of the Bethesda Classification in cervical cancer screening?

Bethesda Classification System for Cervical Cytology

The Bethesda System is the standardized terminology for reporting cervical cytology results in the United States, designed to ensure uniform grading of cellular abnormalities and facilitate clear communication between cytopathologists and clinicians. 1

Primary Purpose and Function

The Bethesda System replaced the numerical Papanicolaou class designations to provide precise, consistent reporting of cervical cytology findings across laboratories and clinical settings. 2 This standardization is essential for:

• Registration and comparison of results over time and between different settings 1
• Quality assurance in cervical cancer screening programs 1
• Guiding clinical management decisions based on risk stratification 1

Laboratories must apply nationally agreed terminology that is translatable into the Bethesda Reporting System, with CIN terminology reserved exclusively for histology. 1

Classification Categories

Specimen Adequacy

The system first addresses whether the specimen is satisfactory for evaluation, which may include qualifiers such as "partially obscuring thick areas" that indicate technical limitations without rendering the specimen unsatisfactory. 3

Squamous Cell Abnormalities (Risk-Stratified)

From lowest to highest cancer risk: 1

• ASC-US (Atypical Squamous Cells of Undetermined Significance): Represents approximately 3.6% of all Pap results and can detect up to 40% of high-grade lesions. 4 This category is more restricted than previous "atypia" designations. 2

• LSIL (Low-Grade Squamous Intraepithelial Lesion): Encompasses HPV-associated cellular changes, mild dysplasia, and CIN I. 2 Nearly 80-85% of LSIL cases are positive for high-risk HPV. 4

• ASC-H (Atypical Squamous Cells—Cannot Exclude HSIL): A subdivision introduced in the 2001 update to identify cells suspicious for high-grade disease. 1, 5

• HSIL (High-Grade Squamous Intraepithelial Lesion): Combines moderate dysplasia, severe dysplasia, carcinoma in situ, and CIN II/III based on their morphologic, behavioral, and virologic similarity. 2

• Squamous Cell Carcinoma: Invasive disease requiring immediate biopsy even if cytology is negative but a visible lesion is present. 1

Glandular Cell Abnormalities

AGC (Atypical Glandular Cells) is a separate category important for detecting glandular preinvasive lesions, with endocervical adenocarcinoma in situ now recognized as a distinct entity. 5, 4

Clinical Application in Screening

Management Algorithm Based on Results

For ASC-US: 4, 6

• High-risk HPV testing for triage (preferred approach)
• If HPV positive → colposcopy
• If HPV negative → routine screening intervals
• Alternative: repeat cytology at 4-6 months for 2 years

For LSIL: 4

• Direct referral to colposcopy (nearly 80-85% are high-risk HPV positive)
• HPV testing not sufficiently selective as initial management for all women with LSIL 1

For ASC-H, HSIL, or AGC: 4, 6

• Immediate colposcopy with directed biopsy
• Management is less controversial for HSIL, with most patients receiving treatment

For invasive carcinoma on cytology: 1

• Biopsy any visible lesion
• Diagnostic excision if no visible lesion

Integration with HPV Testing

High-risk HPV DNA testing has revolutionized the management of atypical cytology. 4 For women aged ≥30 years, cotesting (cytology plus HPV) every 5 years is the preferred screening strategy. 1 However:

• HPV testing should not be used as a stand-alone screening test 1
• Women <30 years should not be screened for HPV due to high viral clearance rates 1
• HPV testing is not recommended for women <20 years for any purpose 1

Quality Assurance Requirements

Laboratories must use CLIA-certified facilities that report findings according to Bethesda 2001 terminology. 1 The system requires:

• Adequate sample collection and preparation 1
• Proper handling, staining, screening, and interpretation 1
• Balance between optimal patient care, quality assurance, and cost-effectiveness 1

Special Population Considerations

Women with HIV have 10-11 times higher risk of abnormal cervical cytology compared to the general population, requiring more vigilant follow-up. 4, 3

Adolescents and young women (<21 years) require special management due to high HPV prevalence and frequent LSIL regression, with different algorithms than older women. 1

Vaccinated women must continue screening according to standard guidelines, as HPV vaccines cover only 70% of cervical cancer-causing types. 1

Critical Implementation Points

The Bethesda System functions as a screening tool to determine which women require colposcopy, not as a definitive diagnostic tool. 7 Colposcopy with directed biopsy remains the gold standard for diagnosis and treatment planning. 1

A common pitfall is that many women equate having a pelvic examination with having a Pap test when no cytology sample was actually obtained—clinics should have protocols to verify documented screening. 1

The system's two-tiered approach (low-grade vs. high-grade SIL) reflects the understanding that cytologic discrimination between CIN II and CIN III is limited and that these lesions behave similarly, requiring comparable management. 2, 7