Format

Send to

Choose Destination
See comment in PubMed Commons below
Future Oncol. 2010 May;6(5):709-16. doi: 10.2217/fon.10.38.

Population fraction of cervical neoplasia attributable to high-risk human papillomaviruses.

Author information

1
National Institute for Health & Welfare, Helsinki & Oulu, Finland.

Abstract

AIMS:

The efficacy of human papillomavirus (HPV) type 16 and 18 vaccines against cervical intraepithelial neoplasia grade II (CIN2+) has been verified, but the active follow-up of studies with invasive cervical cancer or cervical intraepithelial neoplasia grade III (CIN3) as primary end points are ethically not possible. Furthermore, ongoing registry-based passive follow-up studies with invasive cervical cancer as the end point will take time.

MATERIALS & METHODS:

To evaluate the feasibility of CIN3 as a surrogate end point, we compared high-risk (hr) HPV-associated relative risk and population attributable fraction (PAF) of CIN3 and/or squamous cell carcinoma (SCC) estimated in a large serological case-cohort HPV study. Our case-cohort comprised 83 SCC and 389 CIN3 cases and a subcohort of 7862 out of 230,998 Finnish women, who at baseline were under 32 years of age and had undergone a minimum of two pregnancies within 5 years during 1983-1997.

RESULTS:

PAFs of the case-cohort, approach-based, serologically defined and misclassification-corrected HPV16 and hrHPV (HPV types 16, 18, 31 and 33) exposures in the SCC samples were 61% (95% CI: 18-85) and 73% (95% CI: 13-93), respectively. Considerably lower HPV16 and hrHPV PAF estimates in CIN3 of 6% (95% CI: -19-35) and 36% (95% CI: -5-65), respectively, were obtained. A meta-analysis-derived, PCR-based, hrHPV-associated relative risk estimate of 20.3 in CIN2/3+ yielded a PAF estimate for hrHPV in CIN2/3+ of 86% (90% CI: 63-95) in our study population. The former, hrHPV serology-based CIN3 PAF estimates were biased owing to low sensitivity of HPV16 and/or HPV16/18/31/33 serology, most notably in cervical cancer precursor lesions, but the latter estimate overlapped with our hrHPV serology-based cervical cancer PAF estimate.

CONCLUSION:

CIN3 may be a valid surrogate efficacy end point for HPV vaccination studies, but the associated causality of multiple hrHPV exposures needs to be unambigously defined.

PMID:
20465386
DOI:
10.2217/fon.10.38
[Indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Atypon
    Loading ...
    Support Center