Do we need a different strategy for HPV screening and vaccination in East Asia?

Dear Sir, Recently, pooled IARC studies and meta-analyses have showed that at least 13 human papillomavirus (HPV) types, including types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 and 68, are commonly associated with invasive cervical cancer (ICC). Based on HPV type prevalence data from these studies, current HPV vaccines against only HPV16/18 are considered to prevent a majority (>70%) of cervical cancer worldwide. However, HPV data in East Asia have not been fully evaluated in previous pooled and meta-analyses. The present study thus focused on HPV type prevalence in Japan. We performed a meta-analysis of published data to obtain the representative results, and investigated HPV type prevalence and type-specific risks for cervical carcinogenesis in Japan. Furthermore, obtained data were compared with those in China, Korea and other regions. Source articles presenting HPV prevalence data among Japanese women were identified from National Library of Medicine (PubMed). For the meta-analysis, the following inclusion criteria were considered: (i) Studies were published between 1995 and 2005. (ii) Studies had to use PCR-based assays to identify at least 16 strains of HPV6, 11, 16, 18, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59 and 68. (iii) Studies had to include at least 20 HPV-positive women with squamous intraepithelial lesion (SIL), cervical intraepithelial neoplasia (CIN) or ICC. When data or data subsets from an identical study had been published in more than one article, only the publication with the largest sample size was included. However, data from different studies conducted by the same study group were included. Overall, a total of 14 Japanese studies were identified for the present study. For some articles, additional typespecific data were obtained from the authors. HPV type prevalence data were collected separately for squamous cell carcinoma (SCC) and for adenoand adenosquamous carcinoma (ADC). Where histological data were not reported, ICC cases were classified as unspecified carcinoma (UC). On the basis of the pooled analysis of IARC studies, HPV types were separated into 2 groups. High-risk HPVs considered as carcinogenic or probably carcinogenic included HPV16, 18, 26, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 68, 73 and 82; all other HPV types were classified as low-risk types. To evaluate HPV genotype-specific risks for progression from LSIL (low grade SIL) to HSIL (high grade SIL) or more, prevalence ratios [(HSIL 1 ICC):LSIL] and 95% confidence intervals were calculated after adjusting for study area, specimen used for HPV DNA testing, and PCR primers. Logistic regression model was used for statistical adjustment, and the analysis was carried out using JMP 6.0J statistics package (SAS Institute, Cary, NC, USA). The p-values obtained in all tests were considered significant at <0.05. This analysis included 7,262 Japanese women (4,941 normal cytology, 475 LSIL, 720 HSIL and 1,126 ICC) from 14 Japanese HPV studies. Consensus primers for the L1, E6/E7 or E7LCR region or GP5/GP6 primers were employed in these studies. In this meta-analysis, HPV prevalence was 10.2% in women with normal cytology, 79.4% in LSIL, 89.0% in HSIL and 87.4% in ICC. HPV positivity was significantly lower in ADC (69.8%) than in SCC (90.7%). Since overall and typespecific HPV prevalence in UC was very similar to that in SCC, UC cases were combined with SCC cases for comparison of HPV type-specific prevalence by histological type. HPV type distributions by cervical disease were summarized in Table I. In ICC, the most common HPV types were, in order of decreasing prevalence, HPV16 (44.8%), 18 (14.0%), 52 (7.0%), 58 (6.7%), 33 (6.3%), 31 (5.1%), 35 (2.3%), 51 (1.0%) and 56 (0.9%). HPV16 was the predominant type (49.2%) in SCC, although HPV18 was the most prevalent (58.2%) in ADC. On the basis of the comparison of HPV type distributions between LSIL and HSIL/ICC, the type-specific risks for progression from LSIL to HSIL/ICC were analyzed (Table I). HPV16, 18 and 33 conferred a significantly higher risk. Seven types of HPV16/18/31/33/ 35/52/58 (the prevalence ratio; 1.86, 95% CI 1.63–2.15) presented a higher risk of progression than the other high-risk types (0.24, 95% CI 0.17–0.33) and low-risk types (0.18, 95% CI 0.09–0.37). Among Japanese women with ICC, HPV16 and 18 were the most common types, which was consistent with the results from other regions. A pooled analysis demonstrated that HPV16 and 18 were associated with 73.5% of ICC in Southeast Asia, 76.9% in Northern Africa and 71.5% in Europe/ North America, and that HPV52 and 58 were detected in 6.1% of ICC cases in Southeast Asia, 1.5% in Northern Africa and 1.1% in Europe/North America. In Japan, however, HPV16 and 18 were less frequently identified (58.8%), and HPV52 and 58 were more common (13.7%). In China, although HPV16 and 18 were predominant (87.1% of all ICC cases from 5 areas), a multicenter study showed that HPV52 and 58 were locally common in Hong Kong (11.8%) and Guangzhou (southern China, 8.3%). Other small studies also reported