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High-Risk and Low-Risk Human Papillomavirus and the Absolute Risk of Cervical Intraepithelial Neoplasia or Cancer

Thomsen, Louise T. MSc; Frederiksen, Kirsten PhD; Munk, Christian PhD; Junge, Jette MD; Castle, Philip E. PhD; Iftner, Thomas PhD; Kjaer, Susanne K. DMSc

doi: 10.1097/AOG.0000000000000056
Contents: Original Research

OBJECTIVE: To determine the absolute risk of cervical intraepithelial neoplasia (CIN) grade 3 or cervical cancer (CIN 3 or worse) after detection of low-risk human papillomavirus (HPV) and after a negative high-risk HPV test.

METHODS: In this prospective cohort study, consecutive liquid-based cervical cytology samples were collected from women screened for cervical cancer in Copenhagen, Denmark, during 2002–2005. Samples were tested with a clinical test for 13 high-risk and five low-risk HPV types. The cohort (N=35,539; aged 14–90 years) was monitored in a nationwide pathology register for up to 10.5 years for development of CIN 3 or worse.

RESULTS: The 8-year absolute risk of CIN 3 or worse was 1.1% (95% confidence interval [CI] 1.0–1.3%) for HPV-negative women; 1.7% (0.8–2.6%) for low-risk HPV-positive women without concurrent high-risk HPV; 17.4% (16.4–18.5%) for high-risk HPV-positive women without concurrent low-risk HPV; and 15.9% (13.5–18.3%) for women with concurrent high-risk and low-risk HPV. The 8-year absolute risk of CIN 3 or worse after a negative high-risk HPV test (irrespective of low-risk HPV status) was lower than after a normal cytology result among women aged younger than 30 years (3.5% [95% CI, 2.9–4.0%] compared with 6.9% [6.2–7.5%], P<.001) and women aged 30 years or older (0.7% [95% CI, 0.6–0.9%] compared with 1.8% [95% CI, 1.6–2.0%], P<.001).

CONCLUSION: A negative high-risk HPV test provides greater long-term reassurance against CIN 3 or worse than normal cytology. Detection of low-risk HPV does not predict CIN 3 or worse. Cervical cancer screening should not include testing for low-risk HPV types.


Detection of low-risk human papillomavirus in cervical cytology samples does not predict high-grade cervical intraepithelial neoplasia or cervical cancer.

Unit of Virus, Lifestyle and Genes and Statistics, Bioinformatics and Registry, Danish Cancer Society Research Center, and the Gynecologic Clinic, Rigshospitalet, University of Copenhagen, Copenhagen, and the Department of Pathology, Hvidovre Hospital, University of Copenhagen, Hvidovre, Denmark; the Global Cancer Initiative, Chestertown, Maryland; and the University Hospital of Tübingen, Section of Experimental Virology, Tübingen, Germany.

Corresponding author: Susanne K. Kjaer, DMSc, Unit of Virus, Lifestyle, and Genes, Danish Cancer Society Research Center, Strandboulevarden 49, DK-2100 Copenhagen, Denmark; e-mail:

Funded by the Danish Cancer Society, the MERMAID 2 project, and through an institutional grant from Sanofi Pasteur MSD (Lyon, France).

The authors thank Angelika Iftner and Barbara Holz at the University Hospital of Tübingen and the study staff at Hvidovre Hospital for technical and logistic support during data collection and Thor Schütt Svane Nielsen at the Danish Cancer Society for data management.

Presented in part at the 28th International Papillomavirus Conference, December 2–5, 2012, San Juan, Puerto Rico.

Financial Disclosure Ms. Thomsen has received support for conference participation from Sanofi Pasteur MSD. Dr. Munk has received support for conference participation and speakers' fees from Sanofi Pasteur MSD and Merck. Dr. Junge has received advisory board fees and consultant fees from Sanofi Pasteur MSD and Merck. Dr. Castle has served as a paid consultant for BD, Roche, Cepheid, GE Healthcare, and GenProbe/Hologic. He has received HPV tests and reagents for research at reduced or no cost from Qiagen, Roche, Norchip, and mtm. He is a paid member of a data and safety monitoring board for clinical trials of HPV vaccines for Merck. Dr. Iftner has received lecture fees and research grants through his institution from Hologic GmbH and Roche Diagnostics GmBH. Dr. Kjaer has received speakers' and advisory board fees and research grants through her institution from Sanofi Pasteur MSD and Merck. Dr. Frederiksen did not report any conflicts of interest.

© 2014 by The American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.