Lifestyle and socio-demographic factors associated with high-risk HPV infection in UK women

British Journal of Cancer (2007) 97, 133 – 139 & 2007 Cancer Research UK All rights reserved 0007 – 0920/07 $30.00 www.bjcancer.com Lifestyle and socio-demographic factors associated with high-risk HPV infection in UK women SC Cotton*,1,7, L Sharp2,7, R Seth3, LF Masson1, J Little4, ME Cruickshank5, K Neal6 and N Waugh1, on behalf of the TOMBOLA Group 1 Department of Public Health, University of Aberdeen, Polwarth Building, Foresterhill, Aberdeen, Scotland; 2National Cancer Registry Ireland, Elm Court, Boreenmanna Road, Cork, Ireland; 3Histopathology Department, Queen’s Medical Centre, University Hospital NHS Trust, Nottingham, England; 4Canada Research Chair in Human Genome Epidemiology, Department of Epidemiology and Community Medicine, University of Ottawa, Ottawa, Ontario, Canada; 5Department of Obstetrics & Gynaecology, University of Aberdeen, Foresterhill, Aberdeen, Scotland; 6Division of Epidemiology and Public Health, School of Community Health Sciences, University of Nottingham Medical School, Nottingham, England The world age-standardised prevalence of high-risk HPV (hrHPV) infection among 5038 UK women aged 20 – 59 years, with a lowgrade smear during 1999 – 2002, assessed for eligibility for TOMBOLA (Trial Of Management of Borderline and Other Low-grade Abnormal smears) was 34.2%. High-risk HPV prevalence decreased with increasing age, from 61% at ages 20 – 24 years to 14 – 15% in those over 50 years. The age-standardised prevalence was 15.1, 30.7 and 52.7%, respectively, in women with a current normal, borderline nuclear abnormalities (BNA) and mild smear. In overall multivariate analyses, tertiary education, previous pregnancy and childbirth were associated with reduced hrHPV infection risk. Risk of infection was increased in non-white women, women not married/cohabiting, hormonal contraceptives users and current smokers. In stratified analyses, current smear status and age remained associated with hrHPV infection. Data of this type are relevant to the debate on human papillomavirus (HPV) testing in screening and development of HPV vaccination programmes. British Journal of Cancer (2007) 97, 133 – 139. doi:10.1038/sj.bjc.6603822 www.bjcancer.com Published online 22 May 2007 & 2007 Cancer Research UK Keywords: HPV infection; lifestyle factors; cervical cancer *Correspondence: SC Cotton; E-mail: 7 Principal authors who contributed equally to this work. Received 23 February 2007; revised 25 April 2007; accepted 2 May 2007; published online 22 May 2007 factors (e.g. Cuzick et al, 2003; Cuschieri et al, 2004; Moss et al, 2004; Hibbitts et al, 2006; Kitchener et al, 2006). Most infections in women under 30 are transient (Koutsky and Kiviat, 1999; Nobbenhuis et al, 2001; Woodman et al, 2001); infection risk factors, and/or their relative importance, may differ between young and older women. In addition, while cytological smear grade is strongly associated with HPV prevalence (Cuzick et al, 2003; Cuschieri et al, 2004), it is less clear whether the relative contribution of lifestyle risk factors differs by smear grade. We investigated factors associated with prevalence of hrHPV types in a large series of UK women and compared them in younger and older women and by cytological smear grade. MATERIALS AND METHODS Study population Subjects were women assessed for eligibility for TOMBOLA (Trial Of Management of Borderline and Other Low-grade Abnormal smears), a randomised controlled trial (RCT) of alternative management policies and HPV triage (TOMBOLA Group, 2006). Women aged 20 – 59 years, resident in Grampian, Tayside or Nottingham, with a low-grade smear (mild dyskaryosis or borderline nuclear abnormalities (BNA)) taken routinely in the UK national cervical screening programmes (CSPs) during 01/10/ Epidemiology Infection with human papillomavirus (HPV) is necessary for the development of cervical cancer (Walboomers et al, 1999; Bosch et al, 2002). Around 40 HPV types infect mucosal surfaces of the lower genital area (International Agency for Research on Cancer, 2005) and are broadly classified into high- or low-risk for cervical cancer (Munoz et al, 2003). Testing for high-risk HPV (hrHPV) DNA has the potential to improve cervical screening (Brink et al, 2005). In addition, following encouraging trial results (Harper et al, 2004; Villa et al, 2005), two HPV vaccines are under licence. The effectiveness and cost-effectiveness of incorporating HPV testing into screening, and of vaccine programmes, will partly depend on current HPV prevalence, infection patterns and factors associated with infection within specific populations. Human papillomavirus population prevalence mainly depends on patterns of sexual exchange (International Agency for Research on Cancer, 2005), which vary between and within countries, by, for example, birth cohort and ethnic group (Johnson et al, 2001; Fenton et al, 2005). Most available data on HPV prevalence and associated factors are from the United States of America, and/or focus on young women; many series are highly selective and may lack generalisibility. Other series did not examine lifestyle risk Socio-demographic factors and HPV infection SC Cotton et al 134 1999 – 31/10/2003, with no previous treatment for cervical lesions, were eligible for TOMBOLA. Recruitment was in two phases: 01/ 10/1999 – 12/03/2001 and 13/03/2001 – 31/10/2003. During phase one, eligible women had no abnormal smears in the previous 3 years; during phase two, they had up to one BNA smear in the previous 3 years. In phase one, women with a BNA smear were invited to a recruitment clinic approximately 6 months later for a follow-up smear and a swab for HPV testing. Women with a mild smear during both phases, or a BNA smear during phase two, were invited to a recruitment clinic approximately 2 months later and a swab for HPV testing was taken. The swab, an endocervical sample, was taken with a cytobrush; this was immersed in 2 ml of sterile phosphate-buffered saline containing 0.05% thiomersal. A total of 52% of eligible women attended a recruitment clinic, of whom 95% (n ¼ 5514) consented to participate; 27 were subsequently excluded because the smear was inadequate. Five thousand and seventy-four (92%) of the remainder provided an HPV sample. Ethical approval was obtained from the joint Research Ethics Committee of NHS Grampian and the University of Aberdeen, the Tayside Committee on Medical Research Ethics and the Nottingham Research Ethics Committee. Participants provided informed consent. HPV testing Analysis was performed 1 – 4 weeks after swab collection in a single laboratory (Nottingham). Human and viral DNA were extracted using the Qiagen UK kit (Crawley, West Sussex, UK) (QIAamps DNA Mini Kit) following optimisation of the manufacturer’s protocol. Each batch included negative controls containing only elution buffer AE. Extracted DNA was amplified and quantitated by type-specific real-time polymerase chain reaction (PCR) for the housekeeping (...truncated)