Primary cervical cancer screening with human papillomavirus: End of study results from the ATHENA study using HPV as the first-line screening test

- A negative HPV results at baseline predicts one-half the risk of CIN3 + over 3 years than a negative cytology result.
- HPV primary screening with triage using 16/18 genotyping and cytology increases sensitivity to detect CIN3 + 28% over cytology.
- Cytology failed to detect approximately 50% of CIN3 + in women 25-29 years.

ObjectivesATHENA evaluated the cobas HPV Test as the primary screen for cervical cancer in women ≥ 25 years. This reports the 3-year end-of-study results comparing the performance of HPV primary screening to different screening and triage combinations.Methods42,209 women ≥ 25 years were enrolled and had cytology and hrHPV testing. Women with abnormal cytology (≥ atypical squamous cells of undetermined significance) and those HPV positive were referred to colposcopy. Women not reaching the study endpoint of CIN2 + entered the 3-year follow-up phase.Results3-year CIR of CIN3 + in cytology-negative women was 0.8% (95% CI; 0.5-1.1%), 0.3% (95% CI 0.1-0.7%) in HPV-negative women, and 0.3% (95% CI; 0.1-0.6%) in cytology and HPV negative women. The sensitivity for CIN3 + of cytology was 47.8% (95% CI; 41.6-54.1%) compared to 61.7% (95% CI; 56.0-67.5%) for the hybrid strategy (cytology if 25-29 years and cotesting with cytology and HPV if ≥ 30 years) and 76.1% (95% CI; 70.3-81.8%) for HPV primary. The specificity for CIN3 + was 97.1% (95% CI; 96.9-97.2%), 94.6% (95% CI; 94.4-94.8%), and 93.5% (95% CI; 93.3-93.8%) for cytology, hybrid strategy, and HPV primary, respectively. Although HPV primary detects significantly more cases of CIN3 + in women ≥ 25 years than either cytology or hybrid strategy, it requires significantly more colposcopies. However, the number of colposcopies required to detect a single CIN3 + is the same as for the hybrid strategy.ConclusionsHPV primary screening in women ≥ 25 years is as effective as a hybrid screening strategy that uses cytology if 25-29 years and cotesting if ≥ 30 years. However, HPV primary screening requires less screening tests.