HPV as a Primary Screening Tool in Women 25 Years and Older for Risk Assessment of Cervical Cancer

Results of three-year follow-up phase of the ATHENA trial

Three-year follow-up data from the ATHENA trial indicate that human papilloma virus (HPV) primary screening with triage to colposcopy based on genotyping and reflex cytology provides a more sensitive cervical screening strategy than cytology and is more efficient than cotesting. The results were presented at the Plenary session, entitled “Innovative and Practice Changing Concepts in Gynecologic Oncology”, of the 45th Annual Meeting on Women’s Cancer, organised by the Society of Gynecologic Oncology (22-25 March, 2014, Tampa, USA).

The ATHENA study

The study objective was to explore the performance and clinical utility of cervical cancer screening strategies using HPV as the first-line test and to compare HPV-based strategies with cytology-based strategies. The ATHENA trial enrolled 42,209 women 25 years and older, of whom 40,901 were evaluable for this subanalysis.

At enrollment, all women had liquid-based cytology and HPV testing using the cobas HPV Test that detects HPV16 and HPV18 separately and a pool of 12 other high risk HPV types.

Women with abnormal cytology (≥ atypical squamous cells of unknown significance) or high risk HPV-positive were referred for colposcopy. Women undergoing colposcopy who did not have positive cervical intraepithelial neoplasia grade 2 (CIN2+) proceeded to the three-year follow-up phase in which annual cytology and HPV testing were performed.

During follow-up, women with abnormal cytology were referred to colposcopy but did not exit the study unless they had CIN2+ finding. At the three-year visit, all women underwent repeat colposcopy with cervical biopsy. For each strategy, the study investigators determined the total number of cases (baseline and during three-year follow-up) of CIN2+ detected as well as the number of screening tests (liquid-based cytology and/or HPV tests) and the number of colposcopies required to carry out the strategy.

A total of 587 cases with CIN2+ finding were identified at baseline and during the three-year follow-up period. Cytology with atypical squamous cells of unknown significance triage was much less sensitive for CIN2+ than any of the HPV-based strategies.

High risk HPV primary screening with triage to colposcopy based on HPV16/18 genotyping and reflex cytology had an overall sensitivity of 80.0% and detected the most disease at the baseline screening round, but it was somewhat less efficient in terms of the number of colposcopy examinations required to identify an individual case of CIN2+.

Cotesting with both cytology and high risk HPV showed a marginal decrease in sensitivity (77.3%), but required nearly double the number of screening tests.

Cobas HPV Test

On 12 March, 2014, the US Food and Drug Administration (FDA) Microbiology Devices Panel of the Medical Devices Advisory Committee discussed, made recommendations, and voted on a premarket approval application for a new indication for the cobas HPV Test, sponsored by Roche Molecular Systems, Inc.

The cobas HPV Test is a qualitative in-vitro test for the detection of HPV that is currently approved by FDA for use in conjunction with cervical cytology. Roche is seeking a claim whereby the cobas HPV Test can be used as a first-line primary cervical screening test.

The test utilises amplification of target DNA by the polymerase chain reaction and nucleic acid hybridisation for the detection of 14 high risk HPV types in a single analysis. The test specifically identifies types HPV 16 and HPV 18 while concurrently detecting the rest of the high risk types (31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68).

Per the proposed indication, women who test negative for high risk HPV types by the cobas HPV Test would be followed up in accordance with the physician’s assessment of screening and medical history, other risk factors, and professional guidelines.

Women who test positive for HPV genotypes 16 and/or 18 by the cobas HPV Test would be referred to colposcopy. Women who test high risk HPV positive and 16/18 negative by the cobas HPV Test (12 other high risk HPV positive) would be evaluated by cervical cytology to determine the need for referral to colposcopy.

On 13 March 2014, Roche announced that the panel recommended unanimously that the benefits of the cobas HPV Test as a first-line, primary screening tool in women 25 years and older to assess their risk of cervical cancer based on the presence of clinically relevant high risk HPV DNA outweigh the risks.

The panel also voted unanimously that the cobas HPV Test is safe and effective for the proposed indication for use. If approved, the cobas HPV Test would become the first and only HPV test indicated as the first-line primary screen of cervical cancer in the United States.

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