mRNA-Based HPV Assay Performs Well for Triaging Colposcopy Referrals

mRNA-Based HPV Assay Performs Well for Triaging Colposcopy Referrals

The use of APTIMA human papillomavirus (AHPV) assay for the detection of high-risk human papillomavirus E6/E7 oncogenic messenger RNA is an effective triage method for colposcopy referral in women with atypical squamous cells of undetermined significance cytology (ASC-US), according to the results of the Clinical Evaluation of APTIMA mRNA (CLEAR) study.1
The management options for an ASC-US finding on a cervical cancer screening test are referral for colposcopy, repeat cytology, or HPV testing for high-risk strains. However, there has been little consensus about which option is best, partly because the thresholds for referral for colposcopy or additional cytological evaluation were ill-defined.2 In recent years, HPV testing has proved to be the most useful management option in determining appropriate triage of women with ASC-US cytology.3
Previous studies have shown that in comparison with first-generation DNA-based HPV tests, the newer mRNA-based AHPV assay has greater specificity and similar sensitivity for detecting cervical intraepithelial neoplasia grade 2 (CIN2), CIN3, adenocarcinoma in situ, and invasive cervical cancer. “Because the development of HPV-induced cervical cancer is dependent on activity of the viral E6 and E7 oncoproteins, tests that detect the corresponding E6/E7 oncogenic mRNAs have the potential to be more specific than DNA-based tests for the detection of clinically significant disease,” explain the study authors. To expand on these findings, the CLEAR study compared the sensitivity and specificity of the AHPV assay with the DNA-based Hybrid Capture 2 (HC2) assay.
In the CLEAR study, 939 women who had positive ASC-US cytology were deemed “evaluable subjects.” Of these women, 9.7% had CIN2 or greater and 4.4% had CIN3 or greater using the AHPV assay. The sensitivity and specificity of the AHPV assay for CIN2 or greater were 86.8% and 62.9%, respectively; for CIN3 or greater, the sensitivity and specificity were 90.2% and 60.2%, respectively.
In 865 patients, results from both the AHPV and the HC2 assays were available. In a direct comparison of these tests, the study authors found no significant differences in the sensitivity of these assays to detect CIN2 or greater and CIN3 or greater. However, the specificity of the AHPV assay was significantly greater than that of the HC2 assay for both CIN2 or greater and CIN3 or greater (P<.0001).
The clinical implication of these study results could mean that for every 1000 women with ASC-US cytology results and no cervical disease present, about 70 women potentially could be spared a colposcopy if AHPV were used instead of HC2.

Pertinent Points:
- Compared with the DNA-based HC2 assay, the AHPV assay has similar sensitivity but significantly higher specificity for the detection of cervical dysplasia and cancer in women with ASC-US cytology.
- Use of the AHPV assay can prevent unnecessary colposcopic examinations, which could translate to improved effectiveness of and cost savings related to cervical cancer screening programs.


1. Stoler MH, Wright TC, Cuzick J, et al. APTIMA HPV assay performance in women with atypical squamous cells of undetermined significance cytology results. Am J Obstet Gynecol. 2013;208:144.e1-8.
2. Smith-McCune K, Mancuso V, Contant T, Jackson R. Management of women with atypical Papanicolaou tests of undetermined significance by board-certified gynecologists: discrepancies with published guidelines. Am J Obstet Gynecol. 2001;185:551-556.
3. Fey MC, Beal MW. The role of human papilloma virus testing in cervical cancer prevention. J Midwifery Womens Health. 2004;49:4-13.
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