The risk of cervical cancer associated with specific types of human papillomavirus: A case–control study in a UK population

Abstract

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 casecontrol 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 naïve 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 precancer.3-5 The second is the expected reduction in the positive predictive value of cytological screening after introduction of vaccination; this is inevitable as the number of false positives will remain the same while the number of true positives 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 cancer associa...

Long-term CIN3+ risk in women with abnormal cytology; role of hrHPV testing

“…This risk difference was only found in younger women (<30 years), while in older women (⩾30 years) the risks between women positive for HPV16 and women positive for other hrHPV types were similar. This is in line with another study (Powell et al , 2011) that found that the mean age of women with HPV16-associated cancer was significantly lower than of nonHPV16-associated cancer. All CIN3+ in HPV16-positive women were identified within 5 years after detection of abnormal cytology, while lesions associated with other hrHPV types were also found in the 5 years hereafter.…”

“…All CIN3+ in HPV16-positive women were identified within 5 years after detection of abnormal cytology, while lesions associated with other hrHPV types were also found in the 5 years hereafter. This suggests that HPV16 has its main oncogenic effect within a shorter timeframe and at a younger age than other hrHPV types (Safaeian et al , 2009; Powell et al , 2011). …”

Type-specific HPV prevalence in invasive cervical cancer in the UK prior to national HPV immunisation programme: baseline for monitoring the effects of immunisation

“…The methods of specimen selection, preparation and testing in each study were obtained from publications7 21 22 and study leads. A summary of methods of sample preparation and HPV testing is shown in table 1.…”

“…Studies of HPV in cervical cancer and associated high-grade cervical lesions in the years immediately prior to immunisation have been conducted in England, Scotland, Wales7 21 22 and Northern Ireland (unpublished). However, each of these studies (and many from other countries) is limited in numbers to assess subgroups of particular interest, such as cancers in women aged <30 years.…”

Overall efficacy of HPV-16/18 AS04-adjuvanted vaccine against grade 3 or greater cervical intraepithelial neoplasia: 4-year end-of-study analysis of the randomised, double-blind PATRICIA trial

“…HR HPV types 16/18 have the highest type-specific risk of cervical cancer development2 and predominate in 70% of cervical cancer cases worldwide 3…”