The attribution of individual human papillomavirus (HPV) types to cervical neoplasia, especially intraepithelial lesions, varies ethnogeographically. Population-specific data are required for vaccine cost-effectiveness assessment and type replacement monitoring. HPV was detected from 2,790 Chinese women (444 invasive cervical cancers [ICC], 772 cervical intraepithelial neoplasia [CIN] grade 3, 805 CIN2 and 769 CIN1. The attribution of each HPV type found in multiple-type infections was approximated by the fractional contribution approach. Multiple-type infection was common and correlated inversely with lesion severity (54.7% for CIN1, 48.7% for CIN2, 46.2% for CIN3, 27.5% for ICC). Vaccine-covered high-risk types (HPV16/18) attributed to 59.5% of squamous cell carcinoma, 78.6% of adenocarcinoma, 35.9% of CIN3, 18.4% of CIN2 and 7.4% of CIN1. Distinct features compared to worldwide were a higher attribution of HPV52 and HPV58, and a much lower attribution of HPV45. Inclusion of HPV52 and HPV58 in future vaccines would provide the highest marginal increase in coverage with 11.7% for squamous cell carcinoma, 14.4% for CIN3, 22.6% for CIN2 and 17.7% for CIN1. The attribution of HPV types in southern China is different from elsewhere, which should be considered in prioritizing HPV types for vaccine and screening assay development.Cervical cancer is the third most common cancer in women worldwide. 1 Infection with human papillomavirus (HPV) is a necessary, though insufficient, cause of cervical cancer. [2][3][4][5] More than 40 different types of HPV have been detected from the female genital tract, and 15 of them (HPV16,18,31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, 73 and 82) are classified as high-risk based on the epidemiological association with development of cervical cancer. [6][7][8] Two prophylactic vaccines (Cervarix TM by GlaxoSmithKline, United Kingdom; and Gardasil TM by Merck Sharp and Dohme, NJ USA) are currently available for prevention of HPV infection and the subsequent development of cervical neoplasia. Worldwide, about 70-80% of invasive cervical cancers are caused by HPV16 and HPV18, which are covered by both vaccines. 9-12 However, the distribution of non-16/18 HPV types especially among cervical intraepithelial neoplasia varies markedly by geographic region. [13][14][15][16] A population-specific assessment on the prevalence, more importantly the attribution, of each HPV type is essential for policy makers to evaluate the population benefits and cost-effectiveness of the current and next generation vaccines. Such data is also necessary for formulating an HPV-based screening strategy, especially for deciding the spectrum of HPV types to be covered. Furthermore, data acquired before the widespread administration of HPV vaccine is a crucial baseline for monitoring the effectiveness of vaccination at the population level and for detecting HPV type replacement if it ever occurs.

Although a second age-related peak of human papillomavirus (HPV) infection is observed in many populations, it does not seem to have any impact on cervical screening policies. We examined the age-specific prevalence of HPV infection among 2,604 women enrolled for cervical screening and correlated the age at diagnosis of 2,491 cervical intraepithelial neoplasia Grade 2/3 (CIN2/3) lesions and 801 invasive cervical cancers (ICC). Two peaks of HPV infection were detected at 26-30 and 46-50 years, respectively. The first infection peak was followed by a CIN2/3 peak and an ICC peak at 5-15 and 15 years later, respectively. The second infection peak was followed by an ICC peak 20 years later, but strikingly no CIN2/3 peak was detected in between and thus eliminated an opportunity of treating the lesions at preinvasive stages. The most plausible explanation is that women at the expected second CIN2/3 peak (50-65 years) are not having Pap smears under the current opportunistic screening program. Furthermore, women of this age may have physiological retraction of the transformation zone, and CIN lesions may remain undetected if an adequate Pap smear sample is not obtained. To combat this problem, the screening program in Hong Kong needs to focus on women aged 50 years and older and a mop-up screening up to 75 years is necessary. Bimodal peaks of HPV infection and cervical cancer are seen in many countries and the analysis of populationspecific age distribution of CIN2/3 should be an integral exercise in evaluating the effectiveness of a screening program.Human papillomavirus (HPV) infection is a necessary cause of cervical cancer. 1 The infection is mainly transmitted by the sexual route and occurs most commonly in young sexually active individuals with peak prevalence in women younger than 25 years. 2,3 Interestingly, most studies have also observed a second less pronounced peak of infection among older women, mostly 55 years and older. 2 A few hypotheses have been proposed to explain this observation. First, hormonal changes associated with menopause might induce reactivation of latent HPV infection; however, this second peak has not been universally observed in postmenopausal women. Second, it could be attributed to changes in sexual behavior of women and their partners in middle age, but the occurrence of second peak did not correlate well with data on sexual behavior. 2,3 Finally, the second peak may be a reflection of population-specific cohort effects as it is not consistently observed across the world. 2,4 The underlying reason for this second minor peak is still obscure, and its potential importance has not been fully investigated. It has been shown that a3/a15 HPV types, including HPV61, 71, 72, 81, 83, 84 and 89, are more commonly found in cervical scrape samples collected from older women and these samples also contain more squamous cells. 5 Because a3/a15 HPV types are nononcogenic, the significance of the increased prevalence among older women is unclear. 6 Nonetheless, many studies have confirmed a second ...