The risk of cervical cancer associated with specific types of human papillomavirus: a case–control study in a UK population Ned G. Powell 1 , Sam J. Hibbitts 1 , Adam M. Boyde 2 , Robert G. Newcombe 3 , Amanda J. Tristram 1 and Alison N. Fiander 1 1 HPV Research Group, Department of Obstetrics and Gynaecology, School of Medicine, Cardiff University, Cardiff, United Kingdom 2 Department of Pathology, University Hospital of Wales, Heath Park, Cardiff, United Kingdom 3 Department of Primary Care and Public Health, School of Medicine, Cardiff University, Cardiff, United Kingdom Mounting evidence supports incorporation of HPV testing into cervical screening; however, the optimal test format and target population have yet to be confirmed. Assessment of the potential benefits of type-specific testing requires estimation of the risk associated with infection with individual HPV types. However, the risk posed by individual HPV types may be population specific and influenced by cervical screening practice. The existing data on HPV type-specific risk is derived largely from unscreened populations. Our study addressed the lack of data on HPV type-specific risk in cytologically screened populations using a case– control study of 262 invasive cervical cancers diagnosed in Wales between 2000 and 2006, and 8,428 controls who attended for cytological screening in 2004. The analysis showed that the odds ratios (ORs) for infection with HPV 16 and 18 are considerable; 2770 (95% CI 1050–7320) and 950 (95% CI 330–2740), respectively, and that the OR for other oncogenic types are in general considerably less (ranging, where quantified, from 20.2 to 386 in the same population). The effect of age on OR associated with particular HPV types was also assessed; this indicated that infection with a high-risk HPV in women older than 40 years was associated with an approximately 30-fold increased risk of invasive cervical cancer relative to women younger than 40 years. These results indicate that there is significant prognostic information associated with knowledge of HPV type. Human papillomavirus (HPV) is present in the vast majority of invasive cervical cancers and is considered the primary cause of this disease. 1 In the United Kingdom, vaccination to prevent infection with two oncogenic types of HPV (16 and 18) commenced in September 2008, with vaccine being given to 12- to 13-year-old girls born between September 1995 and August 1996. A 2-year catch up program for women aged up to 18 years is also underway. In clinical trials, this vaccine has shown 100% efficacy for prevention of both persistent infection and high-grade cervical intraepithelial neoplasia associated with HPV 16 and 18 in HPV naı ¨ve women. 2 It is likely that cervical screening in the United Kingdom will change substantially in the near future, with two main factors driving this change. The first is the growing body of evidence showing that HPV testing has greater sensitivity than cytological screening for cervical cancer and pre- cancer. 3–5 The second is the expected reduction in the posi- tive predictive value of cytological screening after introduc- tion of vaccination; this is inevitable as the number of false positives will remain the same while the number of true posi- tives will decline. However, there remain many questions regarding how best to use HPV testing. These include whether genotyping for specific HPV types is worthwhile, and what is the significance of a positive HPV test result in different age groups. The objectives of our study were to investigate the potential benefit of HPV genotyping by assessing the risk of cervical can- cer associated with infection with individual HPV types, and to determine the effect of age on estimates of type-specific risk, in a cytologically well-screened UK population. It was necessary to perform these analyses on a popula- tion specific basis as a recent analysis of contemporary archival cervical cancers from the Welsh (UK) population indicated that HPV 16 and 18 were present in 82% of can- cers; which is a higher proportion than previously reported. 6 Estimates of the risks associated with infection with specific HPV types are currently based mainly on case–control stud- ies from populations with smaller proportions of HPV 16/18 associated disease, 7 which suggests that such estimates might not accurately represent the risks associated with HPV infec- tion in UK populations. To address these objectives, the risks posed by infection with specific HPV types were determined using a case–con- trol analysis of HPV infection in recently diagnosed cervical Key words: HPV, type-specific risk, case–control, cervical cancer Grant sponsor: Welsh Office for Research and Development in Health and Social Care; Grant numbers: ReF05/1/014, ReF06/2/224 DOI: 10.1002/ijc.25485 History: Received 7 Dec 2009; Accepted 12 May 2010; Online 25 May 2010 Correspondence to: Ned G. Powell, HPV Research Group, Department of Obstetrics and Gynaecology, School of Medicine, Cardiff University, Cardiff, CF14 4XN, United Kingdom, Tel.: 0044-(0)2920-744742, Fax: 0044-(0)2920-744399, E-mail: powellng@ cf.ac.uk Epidemiology Int. J. Cancer: 000, 000–000 (2010) V C 2010 UICC International Journal of Cancer IJC