Human papillomavirus (HPV) persistence is essential for cervical cancer development. We accrued nested-cohort subjects from a population-based study to investigate the host and viral factors related to outcome of HPV infection. Women (age ≥ 30 years old) with HPV-positive but normal cytology and negative colposcopy were invited to participate. After signing informed consent, every participant completed a structured questionnaire and had 6-monthly follow-ups of Pap smear, HPV testing and colposcopy. Total and type-specific HPV clearance rates as well as host and viral factors associated with clearance in 3-year longitudinal followup were analyzed. Adjusted hazard ratios (HRs) of progression to ≥ cervical intraepithelial neoplasia (CIN) 2 according to baseline HPV of the women with normal cytology were calculated from national registry database. Among the 626 eligible women, 526 (median age 47, 29-75) were enrolled and 412 returned for followup at least once. The median follow-up of enrolled subjects was 23 months (range 6.8-39). The 3-year cumulative total HPV clearance rate was 49.0% (95% confidence interval [CI]: 43.3-54.7%). The median 3-year cumulative type-specific HPV clearance rate was 50.0% (range 0-100.0%) with a median time to clearance of 12.4 months (6.4-24.5). Older age was associated with significantly decreased total HPV clearance and decreased type-specific clearance in HPV-18 and -53, while high viral load was associated with decreased total and type-specific clearance. After adjusting confounding variables, the HR of developing CIN2 in baseline HPVpositive women was 34.0-fold (95% CI: 15.5-74.7) as compared to HPV-negative women. ' 2008 Wiley-Liss, Inc.Key words: human papillomavirus; genotype; viral load; clearance Cervical cancer is one of the leading cancers in female worldwide. 1 There is strong epidemiological and molecular biological evidence indicating that human papillomavirus (HPV) plays a central role in the etiology of cervical cancer. 2,3 Over 90% of cervical cancers and their precursor lesions are attributable to HPV infection. 4,5 However, the prevalence of genital-tract HPV infections has been reported to range from 1.4 to 25.6% in cytologically normal population. 6 It is widely believed that persistent HPV infection is necessary for the development of cervical cancer. 3,7,8 Incorporation of HPV testing into cervical cancer screening has been advocated, although specificity is decreased with expected increase in sensitivity in early detection of high-grade cervical neoplasms. 9-11 However, identifying infection of high-risk HPV causes anxiety in the individual woman. Because of lack of adequate knowledge in predicting outcome, the appropriate management is unclear except periodical follow-up.Several 8,13 HPV variants 17 have been reported associated with HPV persistence/decreased clearance, whereas ever users of oral contraceptives were associated with faster clearance. 15 Multiple infections, viral load 15 and smoking 8 were unrelated to clearance in other longitudinal follow-u...

Highlights d Low-input tagHi-C captures the chromatin structures using hundreds of cells d Compartment and the Rabl configuration are dynamic during hematopoiesis d Gene-body-associating domains (GADs) are general structures of highly expressed genes d Spatial chromatin loops link GWAS SNPs to candidate bloodphenotype genes

We aimed to assess the distribution of human papillomavirus (HPV) genotypes in high-grade cervical lesions in Taiwan. The study included 1,086 paraffin-embedded, formaldehyde-fixed cervical intraepithelial neoplasia (CIN) 2/3 specimens. HPV genotyping was performed using polymerase chain reaction (PCR)-based methods. Multiple HPV types were validated by E6 type-specific PCR, direct sequencing and/or real-time PCR. HPV DNA was detected in 995 (91.6%) specimens, and multiple HPV types were identified in 192 (19.3%) samples. The leading HPV types were HPV16 (24%), HPV52 (20%), HPV58 (20%), HPV33 (13%), HPV31 (8%) and HPV18 (4.6%). Although the leading six types consisted of 87.6%, HPV16 or 18 comprised only 30.9%. The prevalence of different HPV types showed a significant association with age. In women older than 50 yr, HPV16 and 18 comprised 21.3% (83/389), while HPV52, 58 and 33 represented 55.5% (216/389). In women aged less than 50 yr, HPV16 and 18 comprised 32.1% (224/697, p < 0.0001), while HPV 52, 58 and 33 represented 47.9% (334/697, p 5 0.02). The distribution of HPV genotypes was compared with previously reported findings for Taiwanese women with cervical cancer (CC). The overall HPV16 positivity rate was significantly higher in CC than in CIN 2/3 (odds ratio: 2.14, 95% CI: 1.91-2.40). In addition, HPV18, 39 and 45 were significantly overrepresented in CC, whereas HPV52, 58, 33, 31, 35, 51 and 53 were underrepresented. We concluded that an effective vaccine against the most common HPV types could prevent a significant proportion of cervical cancer cases that occur in Taiwan.Human papillomavirus (HPV) is the primary etiologic agent of invasive cervical cancer (CC) and its precursors. 1 HPV DNA testing is a promising alternative or complementary test to improve the efficacy of cervical screening. 1,2 With the advent of the HPV vaccine, data on genotype-specific prevalence of HPV infection would be useful to predict the potential benefits of HPV vaccination. 3,4 Anogenital HPVs can be divided into high- (HPV16,18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68 and 82/MM4) and low-risk groups (HPV6,11, 40, 42, 43, 44, 54, 61, 70, 72, 81 and CP6108) according to the frequency of their presence in patients with cervical carcinoma. 5 In addition, HPV26, 53 and 66 are probably carcinogenic to humans. 5 The distribution of specific HPV genotypes in patients with CC varies greatly across populations. 6 The prevalence of HPV16, 18 and 45 is lower in high-grade squamous intraepithelial lesions (HSIL) than in invasive cancer (prevalence ratio for CC:HSIL 1.30, 95% CI: 1.26-1.34 for HPV16; and 1.76, 95% CI: 1.58-1.95 for HPV18). In contrast, the remaining highrisk types are significantly underrepresented in CC. These differences highlight the importance of HPV type in the risk of progression from HSIL to CC. 7,8 A meta-analysis including 7,094 cases of HSIL from all continents 8 has shown that the 8 most common HPV types in HSIL were broadly similar to those in invasive squamous cell carcinoma, the only exception being ...