When is genotyping for Human Papillomavirus (HPV) not recommended in cases of Atypical Squamous Cells of Undetermined Significance (ASCUS)/Low-grade Squamous Intraepithelial Lesion (LSIL)?

HPV Genotyping is Not Recommended for ASCUS/LSIL Triage

HPV genotyping is not recommended for women with ASCUS or LSIL cytology results to determine who should proceed to colposcopy. 1 Instead, all women with ASCUS who test positive for high-risk HPV should be referred directly to colposcopy, regardless of specific HPV genotype.

Evidence-Based Rationale

The National Comprehensive Cancer Network (NCCN) and American Society for Colposcopy and Cervical Pathology (ASCCP) explicitly recommend against using HPV 16/18-specific DNA testing (genotyping) as a triage tool for women with ASCUS who are already positive for oncogenic HPV high-risk DNA 1. This recommendation is based on several important considerations:

1. Insufficient Risk Stratification: Only approximately 50% of CIN II-positive infections are associated with HPV 16 or 18, meaning that other oncogenic HPV types (e.g., HPV 31,45) still carry a significant risk of approximately 20% for CIN II-positive disease 1.

2. Management Pathway: For women with ASCUS who test positive for any high-risk HPV, the recommended management is colposcopy regardless of specific genotype 1.

3. No Clinical Utility: Genotyping in this context would not alter clinical management decisions, as all high-risk HPV positive women with ASCUS should proceed to colposcopy 1.

Specific Scenarios Where HPV Genotyping Should Not Be Used

1. LSIL Cytology: HPV DNA testing (including genotyping) is not recommended in women with LSIL cytology 1. The ALTS trial showed that LSIL cytology is best managed with colposcopy initially because no useful triage strategy was identified 1.

2. ASC-H or HSIL Cytology: HPV DNA testing is not recommended for women with ASC-H or HSIL cytology 1. These women should proceed directly to colposcopy.

3. Adolescents (< 21 years): HPV testing, including genotyping, is not recommended for adolescents with ASCUS or LSIL 1.

4. STD Screening: HPV DNA testing (including genotyping) should not be used for general STD screening 1.

When HPV Genotyping Is Appropriate

While not appropriate for ASCUS/LSIL triage, HPV genotyping does have specific approved uses:

• Women aged 30 years and older who are high-risk HPV DNA-positive but cytology negative may benefit from HPV genotyping (HPV 16/18) 1.
• This is because HPV 16 and 18 are more oncogenic than other high-risk types, with data suggesting the incidence of CIN III-positive is 17% in women who are HPV 16-positive and 14% in those who are HPV 18-positive, compared to only 3% with other high-risk HPV types 1.

Common Pitfalls to Avoid

1. Overreliance on HPV 16/18: Focusing only on HPV 16/18 for ASCUS/LSIL triage would miss approximately 20% of CIN II-positive disease associated with other oncogenic HPV types 1, 2.

2. Age-Inappropriate Testing: Applying genotyping strategies developed for older women to younger populations, where regression rates are higher 3.

3. Unnecessary Testing: Performing genotyping when it won't change management decisions adds cost without clinical benefit 1.

4. Ignoring Updated Guidelines: The 2019 ASCCP risk-based management guidelines specifically indicate that genotyping was not recommended for ASC-US or LSIL in 2012 guidelines, but colposcopy is recommended for HPV 16/18 positive results in more recent guidelines 1.

By following these evidence-based recommendations, clinicians can avoid unnecessary testing while ensuring appropriate management of women with abnormal cervical cytology results.