What is the recommended management for a 58-year-old female with Human Papillomavirus (HPV) E6/7 positive status?

Management of HPV E6/E7 Positive 58-Year-Old Female

For a 58-year-old female with HPV E6/E7 mRNA positivity, immediate colposcopy with endocervical sampling is strongly recommended due to the high risk of underlying high-grade cervical lesions, even with normal cytology.

Understanding HPV E6/E7 Positivity

HPV E6/E7 mRNA testing detects active oncogenic expression from high-risk HPV types. Unlike standard HPV DNA testing, E6/E7 mRNA positivity indicates:

• Active viral oncogene expression rather than just viral presence
• Higher specificity for clinically significant lesions
• Greater positive predictive value for high-grade dysplasia

Initial Management Algorithm

1. Immediate colposcopy with endocervical sampling 1

   • Required regardless of cytology results
   • E6/E7 positivity indicates active oncogenic expression
   • Do not delay colposcopy as normal cytology does not rule out significant lesions

2. Endometrial sampling

   • Recommended in conjunction with colposcopy for women ≥35 years 2
   • Particularly important at age 58 to rule out endometrial pathology

3. HPV genotyping (if not already done)

   • If HPV 16 or 18 positive: higher risk requires more aggressive management
   • If other high-risk HPV types: still requires colposcopy but slightly lower risk 1

Management Based on Colposcopy Findings

If colposcopy identifies lesions:

• Directed biopsies of all suspicious areas
• If high-grade lesion (CIN2+) is found:
  • Treatment with excisional procedure (LEEP or cold knife conization) 1
  • Cold knife conization preferred if adenocarcinoma in situ (AIS) is suspected

If colposcopy is negative or shows only low-grade lesions:

• For women with E6/E7 mRNA positivity and age >40 years, consider treatment even with negative colposcopy
• The positive predictive value of E6/E7 mRNA testing in women >40 years is 83.7% for HPV 16 and 84.6% for HPV 33 3
• This "test and treat" approach is justified by the high PPV in this age group 4

Follow-up Protocol

If treated for high-grade precancer:

• Initial surveillance with HPV testing or cotesting at 6,18, and 30 months 1
• Long-term surveillance should continue for at least 25 years from initial diagnosis 1

If no high-grade lesion is found:

• For E6/E7 positive women with negative colposcopy: repeat cotesting in 6-12 months 2
• Do not return to routine screening until negative results are confirmed

Important Considerations

• Age factor: At 58 years, the risk of significant disease with E6/E7 positivity is higher
• Post-menopausal status: May affect colposcopic visualization; ensure adequate examination
• Higher specificity: E6/E7 mRNA testing has higher specificity (92.5%) compared to cytology alone 4
• Risk of missed disease: Even with negative colposcopy, the risk of underlying CIN2+ remains significant in E6/E7 positive women

Pitfalls to Avoid

• Do not rely solely on cytology results, as normal cytology does not rule out significant lesions in E6/E7 positive patients 1
• Do not delay colposcopy based on normal cytology findings
• Do not discontinue surveillance too early if treated for dysplasia
• Do not assume negative margins rule out disease if excisional procedure is performed
• Do not use LEEP for suspected AIS without careful consideration due to higher rates of positive margins compared to cold knife conization 1

By following this management approach, you can minimize the risk of missing significant cervical disease in this 58-year-old woman with HPV E6/E7 positivity, while optimizing her outcomes in terms of morbidity, mortality, and quality of life.