HPV DNA testing in population-based cervical screening (VUSA-Screen study): results and implications

Abstract

Background: Human papillomavirus (HPV) testing is more sensitive than cytology for detecting high-grade cervical intraepithelial neoplasia (CIN). We evaluated the performance of high-risk HPV (hrHPV) testing in routine screening.

Methods: In all, 25,871 women (29-61) enrolled in our population-based cohort study were offered both cytology and hrHPV testing. High-risk HPV-positive women with normal cytology and an age-matched subcohort of hrHPV-negative women with normal cytology were invited for repeat testing after 1 and/or 2 years and were referred for colposcopy if they presented with abnormal cytology and/or a positive hrHPV test. The hrHPV-positive women with borderline or mild dyskaryosis (BMD) and all women with moderate dyskaryosis or worse (>BMD) were directly referred for colposcopy. Women with BMD and an hrHPV-negative test were advised to repeat cytology at 6 and 18 months and were referred for colposcopy if the repeat cytology test was abnormal. The main outcome measure was CIN grade 3 or worse (CIN3+). Results were adjusted for non-attendance at repeat testing.

Results: The hrHPV-positive women with abnormal cytology had a CIN3+ risk of 42.2% (95% confidence interval (CI): 36.4-48.2), whereas the hrHPV-positive women with normal cytology had a much lower risk of 5.22% (95% CI: 3.72-7.91). In hrHPV-positive women with normal cytology, an additional cytology step after 1 year reduced the CIN3+ risk to only 1.6% (95% CI: 0.6-4.9) if the repeat test was normal. The CIN3+ risk in women with hrHPV-positive normal cytology was higher among women invited for the first time (29-33 years of age) (9.1%; 95% CI: 5.6-14.3) than among older women (3.0%; 95% CI: 1.5-5.5).

Conclusion: Primary hrHPV screening with cytology triage in women aged 30 years is an effective way to stratify women on CIN3+ risk and seems a feasible alternative to cytological screening. Repeat cytology after 1 year for hrHPV-positive women with normal cytology is however necessary before returning women to routine screening.

Figure 1

Flowchart of the screening profiles of women in the VUSA-Screen study. hrHPV=high-risk human papillomavirus; hrHPV+=positive hrHPV test; hrHPV−=negative hrHPV test; BMD=borderline or mild dyskaryosis; >BMD=moderate dyskaryosis or worse; CIN=cervical intraepithelial neoplasia (grade 2 or 3); Ca=cervical carcinoma. ^*The baseline hrHPV test results of these matched women were blinded.

Figure 2

Age-specific prevalence of hrHPV positivity and cytological abnormalities in women of the VUSA-Screen study. hrHPV=high-risk human papillomavirus; cytological abnormalities=borderline or mild dyskaryosis or worse (⩾BMD).

Figure 3

Cumulative 3-year risk of CIN3+ and CIN2+ stratified by cytology, hrHPV status and HPV16/18 genotype test results adjusted for non-attendance at repeat testing. Abbreviations: hrHPV=high-risk human papillomavirus; hrHPV+=positive hrHPV test; hrHPV−=negative hrHPV test; abnormal cytology, borderline or mild dyskaryosis or worse (⩾BMD); CI=confidence interval; CIN=cervical intraepithelial neoplasia (grade 2 or 3 or higher).