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Cervical Cancer Clinical Trials

ATHENA Landmark Study

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

The ATHENA HPV trial was a large, prospective clinical study 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 study).1,2,3,4 ATHENA, with over 47,000 women enrolled, also set out to evaluate the medical value of testing for pooled high-risk HPV (hrHPV) DNA as well as genotypes HPV 16 and HPV 18 individually.

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

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 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 positive and/or HPV 18 positive women who had ASC-US or who had normal cytology.
  • The ATHENA study 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 study 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

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.
  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.
  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. 5.


IMPACT Trial

The IMPACT (Improving Primary screening And Colposcopy Triage) trial was designed to evaluate a routine cervical cancer screening population in the United States (age 25-65, non-vaccinated and vaccinated from diverse races and ethnicities) with the cobas® HPV Test, CINtec® PLUS Cytology, and CINtec® Histology. The trial enrolled approximately 35,000 women at 32 different clinical centers across the United States. Results were studied in co-testing and primary screening populations identifying more than 5,000 HPV positive women and more than 530 ≥CIN2 disease cases.

The IMPACT trial clinically validated CINtec PLUS Cytology, which received FDA approval in March 2020. CINtec PLUS Cytology is a triage test that uses dual-biomarker technology to simultaneously detect the presence of p16 and Ki-67 within a single cell. The presence of both biomarkers is associated with HPV infections that are transforming and can, if left untreated, progress to pre-cancer or cancer. A positive result of these two biomarkers in a single cell signals that a woman is more significantly at risk for disease. 

Study data will be broadly shared, pending publication of the key findings.

IMPACT

References:

  1. CINtec® PLUS Cytology. Package insert. Roche Diagnostics; 2020.
CERTAIN

The CERTAIN Study

The CERTAIN (CERvical Tissue Adjunctive aNalysis) Study is one of the largest, most rigorous immunohistochemistry clinical studies done to date, evaluating use of the p16 biomarker for clinical/IVD use in the evaluation of cervical biopsy specimens.
 

The CERTAIN Study included:

  • 38,500 interpretations
  • 1,100 biopsies
  • 70 individual surgical pathologists
  • 3 globally recognized expert gynecopathologists

As a result of the CERTAIN Study, CINtec® Histology  achieved ≥ 99% acceptability for staining, morphology, and background. CAP (College of American Pathologists), the ASCCP (American Society for Colposcopy and Cervical Pathology) and WHO (World Health Organization) recommend the adjunctive use of p16 IHC in evaluation of cervical biopsies.2,3

References:

  1. CINtec Histology 510(k). Package insert. Roche Diagnostics; 2017.
  2. Darrah TM, Colgan TJ, Cox JT, et al. The Lower Anogenital Squamous Terminology Standardization Project for HPV-Associated Lesions: background and consensus recommendations from the College of American Pathologists and the American Society for Colposcopy and Cervical Pathology. Arch Pathol Lab Med. 2012;136(10):1266-1297
  3. Stoler M, Bergeron C, Colgan TJ, et al. Tumours of the Uterine Cervix. In: Kurman RJ, Carcangui ML, Herrington CS, Young RH, eds. WHO Classification of Tumours of Female Reproductive Organs. Lyon, France: IARC and WHO; 2014:169-206.