Attribution of human papillomavirus types to cervical intraepithelial neoplasia and invasive cancers in Southern China

Abstract

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.

Human Papillomavirus Type-Specific Prevalence in Women with Cervical Intraepithelial Neoplasm in Western China

“…HPV-45, the third most commonly prevalent genotype in the worldwide scope, is extremely scarce in CIN patients in western China. Thus, in the area with high HPV-58 attribution, inclusion of HPV-58 should be considered in prioritization of HPV types in future vaccines (2). In summary, our study demonstrates a high prevalence of HPV-16 and -58, but not HPV-18 and -45, in cervical precancerous lesions in western China, suggesting an important role of the two HPV genotypes in cervical cancer development in this area.…”

Prevalence, Clinicopathological Characteristics, and Outcome of Human Papillomavirus–Associated Oropharyngeal Cancer in Southern Chinese Patients

“…In view of the relatively higher prevalence of HPV52 in cervical cancer in east Asia (28,29), and the recent report of finding several cases of HPV52 coinfections in OPSCC specimens collected from Beijing, China (30), we chose to use a PCR primer set that has been optimized for HPV-52 detection. However, we did not detect any HPV-52 from our OPSCC specimens.…”

Technical Issues Associated With Estimating the Prevalence of HPV-52 in Cervical Intraepithelial Neoplasia

“…This result is in contrast to several previous reports that indicated parts of Asia had higher rates of HPV-52 associated with CIN II/III than other regions of the world. [10][11][12][13][14][15][16] This apparent discrepancy may have several explanations. The 2014 metaanalysis used a different literature search strategy, including studies in Chinese, and calculated the prevalence of HPV-52 as a proportion of HPV-positive cases only, which may have resulted in differing prevalence estimates.…”

“…6,10 However, HPV-52 prevalence estimates in women vary greatly across differing geographical regions, and several studies from Eastern Asia report it as being the second or third most common HPV type detected in cervical neoplasia. [11][12][13][14][15][16] A recent meta-analysis reported the relative prevalence of HPV-52 to be 16.5% in women with high-grade cervical disease (CIN II/III) and 5.7% in cervical cancers of unspecified histology in Eastern Asia, compared with only 8.1% and 1.8% in Europe. 10 Studies using laser capture microdissection conducted by our group in Australian women estimated the prevalence of HPV-52 in CIN III and cervical cancers to be 4.5% and 2.3%, respectively (manuscripts in preparation).…”