Shang-Ying Hu

Prevalence of human papillomavirus and cervical intraepithelial neoplasia in China: a pooled analysis of 17 population-based studies.

High‐risk (HR) human papillomavirus (HPV) prevalence has been shown to correlate well with cervical cancer incidence rates. Our study aimed to estimate the prevalence of HR‐HPV and cervical intraepithelial neoplasia (CIN) in China and indirectly informs on the cervical cancer burden in the country. A total of 30,207 women from 17 population‐based studies throughout China were included. All women received HPV DNA testing (HC2, Qiagen, Gaithersburg, MD), visual inspection with acetic acid and liquid‐based cytology. Women positive for any test received colposcopy‐directed or four‐quadrant biopsies. A total of 29,579 women had HR‐HPV testing results, of whom 28,761 had biopsy confirmed (9,019, 31.4%) or assumed (19,742, 68.6%) final diagnosis. Overall crude HR‐HPV prevalence was 17.7%. HR‐HPV prevalence was similar in rural and urban areas but showed dips in different age groups: at age 25–29 (11.3%) in rural and at age 35–39 (11.3%) in urban women. In rural and urban women, age‐standardized CIN2 prevalence was 1.5% [95% confidence interval (CI): 1.4–1.6%] and 0.7% (95% CI: 0.7–0.8%) and CIN3+ prevalence was 1.2% (95% CI: 1.2–1.3%) and 0.6% (95% CI: 0.5–0.7%), respectively. Prevalence of CIN3+ as a percentage of either all women or HR‐HPV‐positive women steadily increased with age, peaking in 45‐ to 49‐year‐old women. High prevalence of HR‐HPV and CIN3+ was detected in both rural and urban China. The steady rise of CIN3+ up to the age group of 45–49 is attributable to lack of lesion removal through screening. Our findings document the inadequacy of current screening in China while indirectly raising the possibility that the cervical cancer burden in China is underreported.

Prevalence of type‐specific human papillomavirus in endocervical, upper and lower vaginal, perineal and vaginal self‐collected specimens: Implications for vaginal self‐collection

To determine why a vaginal self‐collection tested for high‐risk human papillomavirus (HR‐HPV) by Hybrid Capture 2® (hc2) has lower sensitivity and specificity for cervical intraepithelial neoplasia Grade 2 or worse (≥CIN 2), we collected 5 specimens (endocervix, upper and lower vagina, perineum, vaginal self‐collection) from 2,625 women. Endocervical and self‐collected specimens had HR‐HPV tests by hc2. All 5 anogenital specimens were tested for 37 HPV genotypes [Linear Array®, (LA)] from 397 women hc2 positive in endocervical or self‐collected specimens and for a randomly selected 71 of 2,228 women hc2 negative on both specimens. Three hundred nintey‐five women who screened positive by hc2 or had abnormal cytology underwent colposcopic evaluation. Of 47 women with ≥CIN 2, hc2 was positive in 97.9% (46/47) of endocervical and 80.9% (38/47), p = 0.008 of self‐collected specimens. Seven of 9 women with ≥CIN 2 and negative self‐collected hc2 tests were positive for HR‐HPV by LA. Of 2,578 women without ≥CIN 2, hc2 was positive in 9.8% (253/2,578) of endocervical and 11.4% (294/2,578), p = 0.001 of self‐collected specimens. Of the 41 more women without ≥CIN 2 that tested hc2 positive on the self‐collected but negative on endocervical specimen, LA tested positive for HR‐HPV in 24, negative for HPV in 11 and negative for HR‐HPV but positive for low‐risk HPV in 6. Lower sensitivity of self‐collected specimens is secondary to lower levels of vaginal HR‐HPV. The principal cause of the lower specificity of self‐collected specimens is HR‐HPV present solely in the vagina, which is not associated with ≥CIN 2.

A multi-center survey of HPV knowledge and attitudes toward HPV vaccination among women, government officials, and medical personnel in China

OBJECTIVES To assess knowledge of HPV and attitudes towards HPV vaccination among the general female population, government officials, and healthcare providers in China to assist the development of an effective national HPV vaccination program. METHODS A cross-sectional epidemiologic survey was conducted across 21 urban and rural sites in China using a short questionnaire. 763 government officials, 760 healthcare providers, and 11,681 women aged 15-59 years were included in the final analysis. Data were analyzed using standard descriptive statistics and logistic regression. RESULTS Knowledge of HPV among the general female population was low; only 24% had heard of HPV. Less than 20% of healthcare providers recognized sexually naive women as the most appropriate population for HPV vaccination. There was high acceptance of the HPV vaccine for all categories of respondents. Only 6% of women were willing to pay more than US

Use of an expanded gold standard to estimate the accuracy of colposcopy and visual inspection with acetic acid

300 for the vaccine. CONCLUSIONS Aggressive education is necessary to increase knowledge of HPV and its vaccine. Further proof of vaccine safety and efficacy and government subsidies combined with increased awareness could facilitate development and implementation of HPV vaccination in China.

Comparison of ThinPrep and SurePath Liquid-Based Cytology and Subsequent Human Papillomavirus DNA Testing in China

We estimate the accuracy of colposcopy and visual inspection with acetic acid (VIA) while minimizing the effects of misclassification bias, and maximizing ascertainment of disease. VIA was performed by experienced physicians on a population‐based sample of women aged 30 to 49 years in rural Shanxi province, China. Each woman received VIA, liquid‐based cytology (LBC) and hybrid capture 2 (hc2, QIAGEN, Gaithersburg, MD; formerly Digene Corporation). Any woman who tested positive on any test had colposcopy, endocervical curettage (ECC) with directed biopsies as necessary and 4‐quadrant random biopsies from normal‐appearing areas of the cervix. A standard diagnosis based on colposcopy and directed biopsy, and an expanded diagnosis including ECC and 4‐quadrant random biopsy were generated for each woman. In 1,839 women, use of the expanded versus the standard diagnostic criteria increased the prevalence of histologically confirmed high‐grade cervical intraepithelial neoplasia and cancer (CIN2+) from 3.2% (59/1,839) to 4.2% (77/1,839) and decreased the sensitivity of VIA for CIN2+ from 69.5% (95% CI: 56.8–79.8) to 58.4% (95% CI: 47.3–68.8%) with little change in specificity of approximately 89%. Compared with the expanded diagnostic criterion, the sensitivity of a visual diagnosis of high‐grade CIN or cancer by a colposcopist was 49.4% (95% CI: 38.2–60.5). The use of an expanded diagnostic criterion in this study yielded more conservative estimates of the sensitivity of VIA and colposcopy.

Prevalence of HPV Infection And Cervical Intraepithelial Neoplasia And Attitudes towards HPV Vaccination among Chinese Women Aged 18-25 in Jiangsu Province

Liquid‐based cytology (LBC) has been compared with conventional cytology in numerous studies. In the current study of 2 LBC systems, the accuracy, rates of unsatisfactory cytology, and sufficiency of residual LBC specimens for Hybrid Capture 2 (HC2) HPV DNA testing were compared.

Liquid-based cytology and human papillomavirus testing: a pooled analysis using the data from 13 population-based cervical cancer screening studies from China.

ObjectiveFew data are available on the epidemiology of HPV and cervical cancer among Chinese women younger than 25 years old. This study aimed to estimate the HPV infection rate and the prevalence of cervical intraepithelial neoplasia (CIN) in women aged 18–25, as well as their knowledge of and attitudes towards HPV vaccination.MethodsA population-based cervical cancer screening study was conducted on women aged 18–25 in Jiangsu province in 2008. Participants provided socio-demographic, reproductive and behavioral information and completed a survey about their knowledge of and attitudes towards HPV vaccination. Women then underwent a gynecologic exam to provide two cervical exfoliated cell samples for high risk HPV DNA testing and liquid-based cytology (LBC) as well as visual inspection with acetic acid (VIA). Women testing positive for any test were referred to colposcopy and biopsy. The gold standard for diagnosis of cervical lesions was directed or random biopsies.ResultsWithin the sample of 316 women, 3.4% of them were diagnosed with CIN grade 2 or worse lesions and 17.1% were found to be positive for HPV DNA. Among these young women, extra-marital sexual behavior of them (OR=2.0, 95%CI: 1.1–3.8) or their husbands (OR=2.6, 95%: 1.4–4.7) were associated with an increased risk of HPV positivity. Although overall HPV awareness was low, after a brief educational intervention, 98.4% reported they would electively receive HPV vaccination and would also recommend that their daughters be vaccinated. However, most urban and rural women reported their ideal maximum out-of-pocket contribution for HPV vaccination to be less than 500 RMB and 50–100 RMB, respectively.ConclusionOur study indicates cervical disease burden is relatively high among sampled Chinese women aged 18–25. Appropriate educational interventions for female adolescents and strategies to subsidize vaccine costs are definitely needed to ensure the effectiveness of vaccination campaigns in China.

Population-based human papillomavirus 16, 18, 6 and 11 DNA positivity and seropositivity in Chinese women.

OBJECTIVE The objective of this study was to evaluate the impact of introducing HR-HPV testing in cytology regarding cervical cancer screening practice. METHODS A pooled analysis of liquid-based cytology (LBC) and HR-HPV testing using data from 13 population-based cervical cancer screening studies conducted in China was performed. Participants (n=25,404) received LBC and HR-HPV testing. Women found to be positive on screening were referred for colposcopy and biopsy. The effectiveness of screening strategies that use: LBC with HR-HPV triage for atypical squamous cells of undetermined significance (ASC-US), HR-HPV testing with cytology triage for HPV positive tests, or LBC and HPV cotesting was compared with that of LBC screening alone. RESULTS LBC with HR-HPV triage for ASC-US had similar sensitivity compared with LBC alone, but significantly increased specificity for both cervical intraepithelial neoplasia grade 2 or worse (CIN2+) and CIN3 or worse (CIN3+) endpoints, and had the best balance between sensitivity and specificity among the strategies. LBC and HR-HPV cotesting had the highest sensitivity and negative predictive value (NPV) and could permit a safe extension of screening intervals. Through the use of an immediate colposcopy threshold of ASC-US or worse for HR-HPV positive women and the use of a raised threshold of low-grade squamous intraepithelial lesion (LSIL) or worse for HR-HPV negative women, LBC and HR-HPV cotesting could provide the same effectiveness as LBC testing with HR-HPV triage for ASC-US at baseline tests. CONCLUSIONS The results of the current study support the use of the cervical cancer screening guidelines in China.

Seroprevalence of human papillomavirus types 6, 11, 16 and 18 in Chinese women.

To optimize HPV vaccination implementation at the population‐level in China, data are needed on age‐specific HPV 16, 18, 6 and 11 prevalence. This cross‐sectional, population‐based study evaluated the age‐ and type‐specific HPV 16, 18, 6 and 11 prevalence of DNA and serum antibodies among women in China. From July 2006 to April 2007, 17–54 year old women from three rural provinces (Xinjiang, Shanxi and Henan) and two cities (Beijing and Shanghai) provided cervical exfoliated cells for HPV DNA and liquid‐based cervical cytology (SurePath). High‐ and low‐risk HPV types were detected with HC‐II (Qiagen), with genotyping of HPV‐positive samples using Linear Array (Roche). HPV 16, 18, 6 and 11 serum antibodies were detected using a Luminex‐based, competitive immunoassay (Merck). A total of 4,206 women with DNA and serum antibody results were included. HPV 16 DNA prevalence peaked in women aged 30–34 (4.2%) and 45–49 yr (3.8%), while HPV 18 DNA prevalence peaked at ages 40–44 yr (1.3%). Most women were dually DNA and serum antibody negative: HPV 16 (92.2%), 18 (97.2%), HPV 16 and 18 (90.2%), 6 (92.0%), 11 (96.6%), 6 and 11(89.9%) and HPV 16, 18, 6 and 11 (82.5%). Future national HPV vaccination programs in China should target younger women due to increased exposure to HPV types 16, 18, 6 and 11 with increasing age. Cumulative exposure of HPV may be underreported in this population, as cross‐sectional data do not accurately reflect exposure to HPV infections over time.

Risk Stratification and Long-term Risk Prediction of E6 Oncoprotein in a Prospective Screening Cohort in China

BackgroundHuman papillomavirus (HPV) seroprevalence data have not previously been reported for different geographical regions of China. This study investigated the cross-sectional seroprevalence of antibodies to HPV 6, 11, 16, and 18 virus-like particles in Chinese women.MethodsPopulation-based samples of women were enrolled from 2006 to 2007 in 3 rural and 2 urban areas of China. Each consenting woman completed a questionnaire and provided a blood sample. Serum antibodies were detected using a competitive Luminex immunoassay that measures antibodies to type-specific, neutralizing epitopes on the virus-like particles.ResultsA total of 4,731 women (median age 35, age range 14-54) were included, of which 4,211 were sexually active women (median age 37) and 520 virgins (median age 18). Low risk HPV 6 was the most common serotype detected (7.3%), followed by HPV 16 (5.6%), HPV 11 (2.9%), and HPV 18 (1.9%). Overall HPV seroprevalence to any type was significantly higher among sexually active women (15.8%) than virgins (2.5%) (P = 0.005). Overall seroprevalence among sexually active women gradually increased with age. Women from rural regions had significantly lower overall seroprevalence (Odds Ratio (OR) = 0.7; 95% CI: 0.6-0.9, versus metropolitan regions, P < 0.001). With increasing number of sexual partners, women were at higher risk of seropositivity of any type (OR = 2.6; 95% CI: 1.7-3.9 for > = 4 partners versus 1 partner, P < 0.001). Wives were at higher risk of seropositivity for HPV 16/18/6/11 when reporting having a husband who had an extramarital sexual relationship (OR = 2.0; 95% CI: 1.6-2.5, versus those whose husbands having no such relationship, P < 0.001). There was a strong association between HPV 16 seropositivity and presence of high-grade cervical lesions (OR = 6.5; 95% CI: 3.7-11.4, versus normal cervix, P < 0.001).ConclusionsHPV seroprevalence differed significantly by age, geography, and sexual behavior within China, which all should be considered when implementing an optimal prophylactic HPV vaccination program in China.