ATHENA Landmark Trial

Shaping our Understanding of the Role of High-Risk HPV Testing in Cervical Cancer Screening  

 

The ATHENA HPV trial was a large, prospective clinical trial evaluating the performance of the cobas® HPV test in three relevant populations*: women with ASC-US (Atypical Squamous Cells of Undetermined Significance) cervical cytology (≥21 years), women with normal cervical cytology (≥30 years), and an overall screening population (25+ years) to explore HPV as a first-line test (longitudinal 3 year trial).1, 2, 3, 4 ATHENA, with over 47,000 women enrolled, also set out to evaluate the medical value of testing for pooled hrHPV DNA as well as genotypes HPV 16 and HPV 18 individually.

 

*Women <25 years (n=4,183) with normal cytology exited the trial.

View the ATHENA Trial Design, Features and Results
ATHENA Infographics

ATHENA Key Findings:

 

The cobas® HPV test was clinically validated in ATHENA, the first screening trial for registration that evaluated simultaneous real-time genotyping of 12 pooled hrHPV genotypes plus HPV 16 and HPV 18 individually. The ATHENA trial evaluated the performance of the cobas® HPV test in multiple clinical situations, including primary screening, ASC-US triage and co-testing (HPV and Pap cytology).

ATHENA not only validated the cobas® HPV test as comparable to the current standard of pooled hrHPV testing within the ASC-US population, but the trial also quantified risk of precancer and cervical cancer in HPV 16+ and/or HPV 18+ women who had ASC-US or who had normal cytology.

The ATHENA trial demonstrated that one in four women who are HPV 16 positive will have cervical disease within three years and that nearly 1 in 7 women with normal Pap cytology who were HPV 16 positive actually had high-grade cervical disease that was missed by cytology.

In addition, results from the ATHENA trial included a comparison of a cobas® HPV test screening strategy to alternative strategies using Pap cytology and HPV testing. The comparison showed that a strategy leveraging the ability of the cobas® HPV test to identify women testing positive for HPV 16 or 18, and using cervical cytology (Pap) as a triage, follow-up test, would allow clinicians to detect more disease without referring a significantly greater number of women to unnecessary follow-up. In 2014, based on ATHENA trial data, the U.S. FDA approved for the first time the use of the Roche cobas® HPV test instead of Pap cytology for first-line primary screening in women 25 and older.

 

ATHENA Principal Publications
 
  • High-risk human papillornavirus testing in women with ASC-US cytology: results from the ATHENA HPV study (Stoler MH, et al. Arn J Clin Pathol. 2011 ;135(3):468-75)
  • Evaluation of HPV-16 and HPV-18 genotyping for the triage of women with high­risk HPV+ cytology-negative results (Wright TC, Jr., et al. Arn J Clin Pathol. 2011; 136(4):578-86)
  • Performance of carcinogenic human papillornavirus (HPV) testing and HPV16 or HPV18 genotyping for cervical cancer screening of women aged 25 years and older a subanalysis of the ATHENA study (Castle PE, Stoler MH, Wright TC Jr, et al. Lancet On col 2011; 12:880-890)
  • The ATHENA human papillomavirus study: design, methods, and baseline results (Wright TC Jr, Stoler MH, Behrens CM, Apple R, Derion T, Wright TL Arn J Obstet Gynecol 2011; 1 :e 1-e 11)
  • Comparison of cervical cancer screening strategies incorporating different combinations of cytology, HPV testing, and genotyping for HPV 16/18 results from the ATHENA HPV study (Cox JT, Castle PE, Behrens CM, et al. Arn J Obstet Gynecol 2012; 184:el-el 1)
  • Primary cervical cancer screening with human papillornavirus: end of study results from the ATHENA study using HPV as the first-line screening test (Wright TC, et al. Gynecol Oncol. 2015;136(2):189-97)
  • Triaging HPV-Positive Women with p16/Ki-67 Dual-stained Cytology Results from a Sub-study Nested into the ATHENA Trial, Wright et al, Gyn Oncology, January 2017 (online 2016)
References
  1. Wright TC, Jr., et al. The ATHENA human papillomavirus study: design, methods, and baseline results. Am J Obstet Gynecol. 2012;206(1):46 e1- e11
  2. Stoler MH, et al. High-risk human papillomavirus testing in women with ASC-US cytology: results from the ATHENA HPV study. Am J Clin Pathol. 2011;135(3):468-75. (for ASC-US CYTOLOGY)
  3. Wright TC, Jr., et al. Evaluation of HPV-16 and HPV-18 genotyping for the triage of women with high-risk HPV+ cytology-negative results. Am J Clin Pathol. 2011;136(4):578-86. (FOR CO-TESTING)
  4. Wright TC, et al. Primary cervical cancer screening with human papillomavirus: end of study results from the ATHENA study using HPV as the first-line screening test. Gynecol Oncol. 2015;136(2):189-97. (FOR PRIMARY SCREENING)