From the Guidelines
For a patient with ASCUS on Pap smear and positive HPV mRNA E6/E7 testing, the recommended follow-up is colposcopy with directed biopsies, as this approach allows for the identification and management of potential high-grade lesions. The presence of HPV E6/E7 mRNA indicates active viral oncogene expression, which carries a higher risk for progression to cervical dysplasia or cancer compared to standard HPV DNA testing alone 1. According to the 2006 consensus guidelines for the management of women with abnormal cervical cancer screening tests, women with ASC-US who are HPV DNA positive should be managed in the same fashion as women with LSIL and be referred for colposcopic evaluation 1.
Key considerations for managing these patients include:
- Colposcopy is recommended for women with ASC-US or greater cytologic abnormality on a repeat test 1
- Endocervical sampling is preferred for women in whom no lesions are identified and those with an unsatisfactory colposcopy 1
- Acceptable postcolposcopy management options of women with ASC-US who are HPV positive, but in whom CIN is not identified, are HPV DNA testing at 12 months or repeat cytologic testing at 6 and 12 months 1
If colposcopy reveals no significant abnormalities or only low-grade lesions, follow-up testing with co-testing (Pap and HPV) is typically recommended in 12 months. If high-grade lesions are found, appropriate treatment such as LEEP (Loop Electrosurgical Excision Procedure) may be necessary. This approach is warranted because while ASCUS itself represents minimal cellular changes, the presence of high-risk HPV oncogene expression significantly increases the risk of underlying precancerous changes that may not be apparent on the initial Pap smear.
From the Research
Recommended Follow-up for Positive HPV mRNA E6/E7 and ASCUS Cells on Pap
- The studies suggest that women with ASCUS and positive HPV mRNA E6/E7 should be referred for colposcopy and further biopsy 2, 3, 4.
- A positive HPV E6/E7 mRNA test result is associated with a higher risk of progressing to CIN2+ in the future 3.
- The sensitivity and specificity of HPV mRNA testing are higher than those of cytology in post-colposcopy follow-up of women with negative cervical biopsy 5.
- HPV E6/E7 mRNA testing can be used as a triage test to identify women with ASCUS who are at high risk of developing CIN2+ 6, 4.
- The use of p16/Ki-67 immunocytochemistry, HPV E6/E7 mRNA testing, and HPV DNA assay can help to define the management of HPV-positive women in cervical cancer screening 6, 4.
- Colposcopy referral or further biopsy is recommended for all ASCUS patients with HPV16/18/45 E6/E7 mRNA positivity and postmenopausal patients with HR-HPV E6/E7 mRNA positivity 2.
Specific Recommendations
- For premenopausal ASCUS patients with other HR-HPV E6/E7 mRNA positivity, colposcopy should be performed if possible, depending on the specific situation 2.
- Women with a negative HPV E6/E7 mRNA testing result can increase follow-up interval, by comprehensively considering their situation, thus avoiding unnecessary colposcopy and reducing the rate of colposcopy and biopsy 3.
- A positive mRNA test post-colposcopy could justify treatment in women above 40 years 5.