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Dermatologic toxicities resulting in dose reduction or discontinuation of treatment pose challenges for targeted anticancer therapies. We conducted this randomized, double-blind, placebo-controlled trial to investigate the efficacy of topical application of Compound Danxiong Granules (CDG) for treatment of dermatologic toxicities associated with targeted anticancer therapies. One hundred and ten patients with dermatologic toxicities induced by targeted anticancer therapies were randomly assigned to CDG or placebo group. Each crude herb (Rhizoma Chuanxiong, Paeonia suffruticosaAndr.,Cortex Phellodendri, Geranium sibiricumL., andFlos Carthami) was prepared as an instant herbal powder. Application of the CDG via topical washes lasted 20 minutes, twice daily, for 10 days. The primary outcome was the total effective rate, defined as reduction in at least one grade of skin toxicity. The total effective rate was 77.61% (52/67) in the CDG group and 27.27% (9/33) in the placebo group (P<0.0001). Compared to the placebo treatment, CDG treatment achieved a higher total effective rate for hand-foot skin reaction (95.45% versus 27.27%), acneiform eruption (69.23% versus 30.78%), and paronychia (68.42% versus 22.22%). Topical application of CDG can effectively attenuate dermatologic toxicities induced by targeted anticancer therapies. The effect of CDG was more pronounced in hand-foot skin reaction.

Objective: To make the clinical evaluation of a solid-state human papillomavirus (HPV) sampling medium in combination with an economical HPV testing method (careHPV TM ) for cervical cancer screening. Methods: 396 women aged 25-65 years were enrolled for cervical cancer screening, and four samples were collected. Two samples were collected by woman themselves, among which one was stored in DCM preservative solution (called "liquid sample") and the other was applied on the Whatman Indicating FTA Elute ® card (FTA card). Another two samples were collected by physician and stored in DCM preservative solution and FTA card, respectively. All the samples were detected by careHPV TM test. All the women were administered a colposcopy examination, and biopsies were taken for pathological confirmation if necessary. Results: FTA card demonstrated a comparable sensitivity of detecting high grade Cervical Intraepithelial Neoplasia (CIN) with the liquid sample carrier for self and physician-sampling, but showed a higher specificity than that of liquid sample carrier for self-sampling (FTA vs Liquid: 79.0% vs 71.6%, p=0.02). Generally, the FTA card had a comparable accuracy with that of Liquid-based medium by different sampling operators, with an area under the curve of 0.807 for physician &FTA, 0.781 for physician &Liquid, 0.728 for self & FTA, and 0.733 for self &Liquid (p>0.05). Conclusions: FTA card is a promising sample carrier for cervical cancer screening. With appropriate education programmes and further optimization of the experimental workflow, FTA card based self-collection in combination with centralized careHPV TM testing can help expand the coverage of cervical cancer screening in low-resource areas.

Background: It is important to understand the natural history of cervical cancer, which has implications for cancer prevention and management. However, a dearth of studies on the long-term development of cervical cancer exists in China. Methods: We investigated the natural history of cervical cancer in Chinese women by creating a multistate model using 11 years of follow-up data from the Shanxi Province Cervical Cancer Screening Study I conducted from 1999 to 2010. In 1999, a total of 1,997 eligible women, ages 35 to 45 years, were enrolled in Xiangyuan County, Shanxi Province. Participants were followed up in 2005 and 2010, respectively. Results: The average time a subject spent in CIN1 before transiting into another state was 1.4693 years [95% confidence interval (CI): 1.1215–1.9251] and the average time a subject spent in CIN2 was 2.9822 years (95% CI: 1.9790–4.4938). A subject's transition probability from CIN1 to normal increased with time. However, the transition probability from CIN1 to CIN2 was relatively lower, with 3-, 5-, and 10-year transition probabilities of 0.1415, 0.1066, and 0.0437. Comparison of 5-year transition probabilities between CIN2 to normal/CIN1 and CIN2 to CIN3+ yielded a ratio of 2.74. Conclusions: Women with CIN1 had a substantial tendency for regression. Similarly, women with CIN2 had a higher probability of regression to normal/CIN1 than progression to CIN3+. Findings in this study may have significant implications for the development and evaluation of formal cervical cancer preventive strategies in China. Impact: This study may serve as a valuable reference to future research on other multistate cancer processes. Cancer Epidemiol Biomarkers Prev; 23(7); 1298–305. ©2014 AACR.

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.

BACKGROUND Liquid-based cytology (LBC) has been widely used for cervical cancer screening. Despite numerous studies and systematic reviews, to the authors' knowledge few large studies to date have focused on biopsy-confirmed cervical lesions and controversy remains concerning its diagnostic accuracy. The objective of the current study was to assess LBC for detecting biopsy-confirmed cervical intraepithelial neoplasia (CIN) and cancer. METHODS A pooled analysis of LBC using data from 13 population-based, cross-sectional, cervical cancer screening studies performed in China from 1999 to 2008 was performed. Participants (n = 26,782) received LBC and human papillomavirus testing. Women found to be positive on screening were referred for colposcopy and biopsy. The accuracy of LBC for detecting biopsy-confirmed CIN of type 2 or worse (CIN2+) as well as CIN type 3 or worse (CIN3+) lesions was analyzed. RESULTS Of 25,830 women included in the analysis, CIN2+ was found in 107 of 2612 with atypical squamous cells (4.1%), 142 of 923 with low-grade squamous intraepithelial neoplasia (15.4%), 512 of 784 with high-grade squamous intraepithelial neoplasia (65.3%), 29 of 30 with squamous cell carcinoma (96.7%), 4 of 27 with atypical glandular cells (14.8%), and 85 of 21,454 with normal cytology results (0.4%). No invasive cancers were found to have atypical squamous cells, atypical glandular cells, or cytologically normal slides. The overall sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of LBC for detecting CIN2+ were 81.0%, 95.4%, 38.3%, 99.3 %, and 94.9%, respectively. Although Hybrid Capture 2 was more sensitive than LBC, the specificity, positive predictive value, and overall accuracy of LBC were higher than those of Hybrid Capture2 at 85.2%, 18.6%, and 85.5%, respectively. CONCLUSIONS The results of the current study indicate that the performance of LBC can effectively predict the risk of existing CIN2+ and may be a good screening tool for cervical cancer prevention in a developing country. Cancer (Cancer Cytopathol) 2013;121:473-82. © 2013 American Cancer Society.

International collaborative training programs for graduate students are widespread, but studies on their educational impact are limited. As an advanced cancer institute in China, Cancer Hospital Chinese Academy of Medical Science (CHCAMS) attaches great importance to international exchanges and cooperation within graduate education. The Department of Epidemiology of CHCAMS has been involved in several existing international training programs and has also launched a short-term training program in cooperation with foreign universities and institutes from 2008. Fogarty International Clinical Research Scholars and Fellows (FICRS-F) Program and the Fulbright-Fogarty Fellowship Program are the most typical examples of our practice in international cooperation on graduate education over these years. Our department has gained substantial experience in graduate-level international collaborative training, focused on cancer epidemiology. This paper is a brief introduction to the practice of different programs in our department and students’ achievements during and after training. Moreover, we attempt to serve as a reference and help promote the training of graduate students pursuing careers in cancer research or global health by other universities or research institutes.

Objective We performed a pooled analysis to examine cigarette smoking and household passive smoke exposure in relation to the risk of human papillomavirus (HPV) infection and cervical intraepithelial neoplasia grade 2+ (CIN2+). Methods Data were pooled from 12 cross-sectional studies for cervical cancer screenings from 10 provinces of China in 1999-2007. A total of 16,422 women were analyzed, along with 2,392 high-risk-HPV (hr-HPV) positive women and 381 CIN2+ cases. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression models controlling for sexual and non-sexual confounding factors. Results There was an excess risk between active smoking and hr-HPV infection and CIN2+. Adjusted OR for ever smokers vs. never smokers was 1.45 (95% CI=1.10-1.91), for hr-HPV infection and 1.89 (95% CI=1.03-3.44), for CIN2+. Passive smoking had a slightly increased risk on the hr-HPV infection with adjusted OR 1.11 (1.00-1.24), but no statistical association was observed between passive smoke exposure and CIN2+. Compared with the neither active nor passive smokers, both active and passive smokers had a 1.57-fold (95% CI=1.14-2.15) increased risk of HPV infection and a 1.99-fold (95% CI=1.02-3.88) risk of CIN2+. Conclusion Our large multi-center cross-sectional study found active smoking could increase the risk of overall hr-HPV infection and CIN2+ adjusted by passive smoking and other factors. Passive smoking mildly increased the risk of HPV infection but not the CIN2+. An interaction existed between passive tobacco exposure and active smoking for hr-HPV infection and the CIN2+.

Objective To explore the genotype distribution of high-risk human papillomavirus (HR-HPV) and its attribution to different grades of cervical lesions in rural China, which will contribute to type-specific HPV screening tests and the development of new polyvalent HPV vaccines among the Chinese population. Methods One thousand two hundred ninety-two subjects were followed based on the Shanxi Province Cervical Cancer Screening Study I (SPOCCS-I), and screened by HPV DNA testing (hybrid capture® 2 [HC2]), liquid-based cytology (LBC), and if necessary, directed or random colposcopy-guided quadrant biopsies. HPV genotyping with linear inverse probe hybridization (SPF10-PCR-LiPA) was performed in HC2 positive specimens. Attribution of specific HR-HPV type to different grades of cervical lesions was estimated using a fractional contribution approach. Results After excluding incomplete data, 1,274 women were included in the final statistical analysis. Fifteen point two percent (194/1,274) of women were HR-HPV positive for any of 13 HR-HPV types (HPV16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68) and the most common HR-HPV types were HPV16 (19.1%) and HPV52 (16.5%). The genotypes most frequently detected in HR-HPV-positive cervical intraepithelial neoplasia grade 1 (CIN1) were HPV52 (24.1%), HPV31 (20.7%), HPV16 (13.8%), HPV33 (13.8%), HPV39 (10.3%), and HPV56 (10.3%); in HR-HPV-positive cervical intraepithelial neoplasia grade 2 or worse (CIN2+): HPV16 (53.1%), HPV58 (15.6%), HPV33 (12.5%), HPV51 (9.4%), and HPV52 (6.3%). HPV52, 31, 16, 33, 39, and 56 together contributed to 89.7% of HR-HPV-positive CIN1, and HPV16, 33, 58, 51, and 52 together contributed to 87.5% of CIN2+. Conclusion In summary, we found substantial differences in prevalence and attribution of CINs between different oncogenic HPV types in a rural Chinese population, especially for HPV16, 31, 33, 52, and 58. These differences may be relevant for both clinical management and the design of preventive strategies.

As China's population ages, the importance of determining prevalence of cervical disease and accurate cervical cancer screening strategies for postmenopausal women is increasing. Seventeen population-based studies were analyzed to determine prevalence of cervical neoplasia in postmenopausal women. All women underwent HPV DNA testing, visual inspection with acetic acid (VIA) and cytology testing. Diagnostic values for primary and combinations screening methods included sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), referral rate and area under curve (AUC) were calculated using directed biopsy or four quadrants biopsy as reference standard. Premenopausal and postmenopausal women had equal HPV infection and cervical neoplasia rates (p 0.05). HPV DNA testing CIN3+ sensitivity, specificity, PPV, NPV, referral rate and AUC were 97.9% (95% CI: 90.2-99.9%), 84.2% (95% CI: 82.8-85.5%), 9.9% (95% CI: 7.4-12.8%), 100% (95% CI: 99.8-100%), 17.2% (95% CI: 15.9-18.7%), 0.911, respectively. VIA values were 41.7% (95% CI: 28.4-55.9%), 94.5% (95% CI: 93.6-95.3%), 11.8% (95% CI: 7.5-17.3%), 98.9% (95% CI: 98.5-99.3%), 6.2% (95% CI: 5.3-7.1%) and 0.681, respectively. Values for VIA with HPV triage were 39.6% (95% CI: 26.6-53.8%), 99.2% (95% CI: 98.8-99.5%), 45.2% (95% CI: 30.8-60.4%), 98.9% (95% CI: 98.5-99.3%), 1.5% (95% CI: 1.1-2.0%) and 0.694, respectively. VIA and HPV DNA co-test values were 100% (95% CI: 94.0-100%), 79.5% (95% CI: 78.0-81.0%), 8.0% (95% CI: 6.0-10.3%), 100% (95% CI: 99.9-100%), 21.9% (95% CI: 20.4-23.4%) and 0.898, respectively. VIA sensitivity decreases significantly in postmenopausal women compared to premenopausal performance. HPV DNA testing maintains performance between pre- and postmenopausal women and is the most accurate primary modality for screening postmenopausal populations in low resource areas of China.

Background The cost-effectiveness of human papillomavirus (HPV) vaccination in women pre-sexual debut has been demonstrated in many countries. This study aimed to estimate the cost-effectiveness of a 3-dose bivalent HPV vaccination at ages 12 to 55 year in both rural and urban settings in China. Methods The Markov cohort model simulated the natural history of HPV infection and included the effect of screening and HPV vaccination over the lifetime of a 100,000 female cohort. Transition probabilities and utilities were obtained from published literature. Cost data were estimated by Delphi panel using healthcare payers’ perspective. Vaccine cost was assumed Hong Kong listed price. Vaccine efficacy (VE) was based on the PATRICIA trial data assuming VE irrespective of HPV type at all ages on incident HPV. Costs and outcomes were discounted at 3 %. Cervical cancer cases and incremental cost-effectiveness ratio (ICER) for vaccination and screening compared with screening alone were estimated for each vaccination age. Reduced VE in women post-sexual debut were investigated in scenario analyses. Results With 70 % vaccination coverage, a reduction of cancer cases varying from 585 to 33 in rural and 691 to 32 in urban were estimated at ages 12 to 55, respectively. The discounted ICERs of vaccination at any age under 23 years in rural and any age under 25 years in urban were lower than the current threshold. Scenario analyses with lower VE post-sexual debut confirmed the results with age 20 in rural and 21 in urban had consistent lower ICERs. The more ‘catch-up’ cohorts vaccinated at the start of a program, the more cancer lesions are avoided in the long-term. Conclusions Vaccination at any age under 23 years old in rural and any age under 25 years old in urban were cost-effective. Catch-up to the age of 25 years in rural and urban could still be cost-effective. Electronic supplementary material The online version of this article (doi:10.1186/s12885-016-2207-3) contains supplementary material, which is available to authorized users.

Objective : Cervical cancer is the second most common cancer among women worldwide, and over 85% of cervical cancers occur in developing countries such as China. Lack of resources for nationwide cervical cancer screening in China makes vaccination against oncogenic strains of HPV particularly important. Knowledge of age at sexual debut and sexual behavior is essential prior to implementation of a national vaccination program. Methods and materials : A cross-sectional epidemiologic survey was conducted across 21 urban and rural sites in China to assess age at sexual debut and sexual behavior. 98.6% of the 11,852 recruited women aged 15–59 years were included in the analysis. Data were collected using a short, nurse-administered questionnaire and analyzed using standard descriptive statistics and survival analysis. Results : In urban areas, more than ten percent of the 15–19 year old age group were already sexually active at the time of interview; this number increased to nearly 44% in the 20–24 year old age group. Chinese young women with an occupation were more likely to be sexually active compared to female students of the same age, irrespective of area of residence. The crude median sexual debut age for the youngest age group was 17 years, earlier than the sexual debut age reported by older cohorts. Younger age cohorts had an earlier menarche age than older cohorts and were more likely to have more sexual partners than older women, and more likely to have partners with more than one female partner. Conclusion : There is a trend towards earlier sexual debut and riskier sexual behaviors in younger age groups of Chinese women. These findings suggest that HPV vaccination of women between the ages of 13 and 15 years, before the completion of national compulsory education, is likely to contribute to the prevention of HPV infection and cervical cancer in China.

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 to 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 and Co). 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 years (3.8%), while HPV 18 DNA prevalence peaked at ages 40–44 years (1.3%). Most women were dually DNA and serum antibody negative: HPV 16 (92.2%), 18 (97.2%), HPV 16 & 18 (90.2%), 6 (92.0%), 11 (96.6%), 6 & 11(89.9%), and HPV 16, 18, 6, & 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 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.

Worldwide, one-seventh of cervical cancers occur in China, which lacks a national screening program. By evaluating the diagnostic accuracy of self-collected cervicovaginal specimens tested for human papillomavirus (HPV) DNA (Self-HPV testing) in China, we sought to determine whether Self-HPV testing may serve as a primary cervical cancer screening method in low-resource settings.We compiled individual patient data from five population-based cervical cancer-screening studies in China. Participants (n = 13 140) received Self-HPV testing, physician-collected cervical specimens for HPV testing (Physician-HPV testing), liquid-based cytology (LBC), and visual inspection with acetic acid (VIA). Screen-positive women underwent colposcopy and confirmatory biopsy. We analyzed the accuracies of pooled Self-HPV testing, Physician-HPV testing, VIA, and LBC to detect biopsy-confirmed cervical intraepithelial neoplasia grade 2 or more severe (CIN2+) and CIN3+. All statistical tests were two-sided.Of 13 004 women included in the analysis, 507 (3.9%) were diagnosed as CIN2+, 273 (2.1%) as CIN3+, and 37 (0.3%) with cervical cancer. Self-HPV testing had 86.2% sensitivity and 80.7% specificity for detecting CIN2+ and 86.1% sensitivity and 79.5% specificity for detecting CIN3+. VIA had statistically significantly lower sensitivity for detecting CIN2+ (50.3%) and CIN3+ (55.7%) and higher specificity for detecting CIN2+ (87.4%) and CIN3+ (86.9%) (all P values.001) than Self-HPV testing, LBC had lower sensitivity for detecting CIN2+ (80.7%, P = .015), similar sensitivity for detecting CIN3+ (89.0%, P = .341), and higher specificity for detecting CIN2+ (94.0%, P.001) and CIN3+ (92.8%, P.001) than Self-HPV testing. Physician-HPV testing was more sensitive for detecting CIN2+ (97.0%) and CIN3+ (97.8%) but similarly specific for detecting CIN2+ (82.7%) and CIN3+ (81.3%) (all P values.001) than Self-HPV testing.The sensitivity of Self-HPV testing compared favorably with that of LBC and was superior to the sensitivity of VIA. Self-HPV testing may complement current screening programs by increasing population coverage in settings that do not have easy access to comprehensive cytology-based screening.

Via a large population-based survey conducted in rural, southwestern China, we aim to evaluate the effect of visual inspection with acetic acid/Lugol’s iodine (VIA/VILI) on diagnosing cases of cervical cancer and of pre-cancerous lesions while exploring the mode of cervical prevention and control in low-resource settings in China. Women aged 30–59 years from Chongqing, China were recruited from 2006 to 2009. Participants underwent VIA/VILI, and, if positive, received colposcopy-directed or random biopsies. Women with negative VIA/VILI or biopsy-confirmed cervical intraepithelial neoplasia (CIN) 1 lesions diagnosed in the first round of screening were re-screened in the following year with the same procedure. In total, 10,269 women received VIA/VILI. The average age of participants was 40.9 ± 7.6 years. Overall, 0.85% (87/10,269) of women were diagnosed via pathology-confirmed biopsy with CIN1, 0.25% (26/10,269) with CIN2, 0.27% (28/10,269) with CIN3, and 0.02% (2/10,269) with cervical cancer. Over half (57.7%) of CIN2 lesions, the majority of CIN3 lesions (89.3%), and all cancer cases (100%) were detected in the first round of screening. In a rural, low-resource setting in China, one-time VIA/VILI screening detected more than a half of CIN2 cases, most CIN3 cases and all the cervical cancer cases. Detection rates of CIN2 lesions significantly increased with a 1-year follow-up VIA/VILI screen. Therefore, if multiple cervical cancer screenings are not feasible logistically or financially, a one-time VIA/VILI may be the most efficient strategy to detect cervical cancer and most CIN3 lesions in women in low-resource settings.

The objectives of this study were to compare the sensitivity of colposcopically directed biopsy (biopsy of cervical quadrants with colposcopic impressions of human papillomavirus, cervical intraepithelial neoplasia [CIN], or cancer) for CIN 3 or cancer (CIN 3+) among physicians and to estimate the increase in yield of CIN 3+ per colposcopy associated with "random" biopsies and/or endocervical curettage (ECC).Two studies in which 7 physicians performed 1,383 colposcopic examinations on women with abnormal cervical cytology were reviewed. At colposcopy, the cervix was divided into quadrants by lines from the 12- to the 6-o'clock and from the 3- to the 9-o'clock positions. Each quadrant was assigned a colposcopic impression of normal, human papillomavirus or CIN 1, CIN 2 or CIN 3, or cancer. Each quadrant had biopsy of colposcopically detected lesions or "random" biopsy at the squamocolumnar junction if the colposcopic impression was normal. Lastly, ECC was obtained.Among the physicians, the sensitivity of colposcopically directed biopsy for CIN 3+ varied from 28.6% to 92.9% (p.001). With logistic regression, the sensitivity of colposcopically directed biopsy for CIN 3+ increased as the number of cervical quadrants with CIN 3+ increased (p.001); once corrected for the number of quadrants with CIN 3+, differences between the physician's sensitivities remained significant (p = .01). For 6 of 7 physicians, the yield of CIN 3+ per colposcopy was greater when colposcopically directed biopsy was augmented by up to 4 "random" biopsies plus ECC (p = .03 to p.001).The sensitivity of colposcopy for CIN 3+ varies widely. Performing up to 4 "random" biopsies plus ECC increases the yield of CIN 3+.

Controversy remains over whether high-risk human papillomavirus (HPV) DNA testing should be used as a primary screen for cervical cancer. The aims of our study were to assess whether HPV DNA testing could be applied to cervical-cancer screening programmes in China, as well as other similar developing countries.We did a pooled analysis of population-based cervical cancer screening studies done in mainland China from 1999 to 2008 with concurrent HPV DNA testing (Hybrid Capture 2 assay; Qiagen, Gaithersburg, MD, USA), liquid-based cytology (LBC), and visual inspection with acetic acid (VIA). Eligible women were sexually active, not pregnant, had an intact uterus, and had no history of cervical intraepithelial neoplasia (CIN), cervical cancer, or pelvic irradiation. All women positive for any test were referred for colposcopy and biopsy. Cervical lesions were diagnosed by directed or random biopsy. We assessed the diagnostic accuracy of HPV DNA testing for the detection of CIN grade 3 or greater.30,371 women from 17 cross-sectional, population-based studies in various parts of China were screened. 1523 women were subsequently excluded because of inadequate HPV DNA specimens or they did not have a biopsy taken, which included women with atypical squamous cells of undetermined significance; low-grade squamous intraepithelial lesion or worse; positive HPV, negative cytology, and missing or positive colposcopy results; and unsatisfactory cytology results. HPV DNA testing had a higher sensitivity of 97·5% (95% CI 95·7-98·7) for detection of CIN grade 3 or worse, and a lower specificity of 85·1% (82·3-87·9), compared with cytology (sensitivity 87·9% [95% CI 84·7-90·7], specificity 94·7% [93·5-96·0]) and VIA (54·6% [48·0-61·2], 89·9% [86·8-93·0]). Sensitivity did not vary by study or age (35 years, 35-49 years, ≥50 years); however, specificity did vary with age (p0·0001) and was highest in women younger than 35 years (89·4%; 95% CI 86·1-91·5). An increase in the positive cutoff point from the manufacturer recommended 1 pg/mL to 2 pg/mL led to a decrease in the overall HPV DNA positivity from 16·3% to 13·9% (p0·0001), which could result in a decrease in referral rates, although sensitivity was slightly lower (97·5% to 95·2%). An increase in the cutoff point to 10 pg/mL in women younger than 35 years maintained a high sensitivity 97·7% (95% CI 87·7-99·9) and increased specificity to 93·5% (95% CI 91·9-94·6).HPV DNA testing is highly sensitive and moderately specific for CIN grade 3 or worse, with consistent results across study sites and age groups-including women younger than 35 years. A rise in the cutoff point might be beneficial for future screening programmes in China, especially when screening women younger than 35 years.

The causal relationship between persistent high-risk human papillomavirus infection and cervical cancer is widely accepted. HR-HPV DNA testing, alone or in combination with Pap smear testing, may have a role in primary screening. The screening results (VIA, VILI, Pap, and HR-HPV DNA) of 9,057 women in rural China were analyzed to determine the screening performance for the detection of CIN3+. All screening strategies had comparable AUCs (0.9). Cotesting strategies had the overall highest sensitivity for CIN3+ (99.4%), followed by HR-HPV DNA testing alone (96.3%), Pap alone (80.2%), and reflex testing (75.4%). Reflex testing had the highest specificity (96.7%), followed by Pap alone (93.3%), HR-HPV DNA testing alone (85.5%), and both cotesting strategies (LSIL: 84.8%, HSIL: 84.8%). Of the single-test strategies, HR-HPV DNA testing had a higher sensitivity (96.3% vs. 80.2%) compared with Pap testing. The specificity of the Pap test was higher (93.3% vs. 85.5%) and it had a lower percent referred for colposcopy (7.8% vs. 15.8%) than HR-HPV DNA testing. HR-HPV DNA testing with a 10.0 cutoff point (relative light units/cutoff ratio) had a sensitivity (85.2%) and specificity (90.6%) estimate comparable to Pap testing. A single-test primary screening strategy with adequate performance would permit less frequent screening and be most appropriate. Of the primary screening strategies investigated in this setting in China, the performance of HR-HPV DNA testing with an increased cutoff-point might best meet these criteria.

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.

Background Liquid-state specimen carriers are inadequate for sample transportation in large-scale screening projects in low-resource settings, which necessitates the exploration of novel non-hazardous solid-state alternatives. Studies investigating the feasibility and accuracy of a solid-state human papillomavirus (HPV) sampling medium in combination with different down-stream HPV DNA assays for cervical cancer screening are needed. Methods We collected two cervical specimens from 396 women, aged 25–65 years, who were enrolled in a cervical cancer screening trial. One sample was stored using DCM preservative solution and the other was applied to a Whatman Indicating FTA Elute® card (FTA card). All specimens were processed using three HPV testing methods, including Hybrid capture 2 (HC2), careHPV™, and Cobas®4800 tests. All the women underwent a rigorous colposcopic evaluation that included using a microbiopsy protocol. Results Compared to the liquid-based carrier, the FTA card demonstrated comparable sensitivity for detecting high grade Cervical Intraepithelial Neoplasia (CIN) using HC2 (91.7 %), careHPV™ (83.3 %), and Cobas®4800 (91.7 %) tests. Moreover, the FTA card showed a higher specificity compared to a liquid-based carrier for HC2 (79.5 % vs. 71.6 %, P = 0.015), comparable specificity for careHPV™ (78.1 % vs. 73.0 %, P > 0.05), but lower specificity for the Cobas®4800 test (62.4 % vs. 69.9 %, P = 0.032). Generally, the FTA card-based sampling medium’s accuracy was comparable with that of liquid-based medium for the three HPV testing assays. Conclusions FTA cards are a promising sample carrier for cervical cancer screening. With further optimization, it can be utilized for HPV testing in areas of varying economic development.

Background Controversy remains whether a pattern of cervical intraepithelial neoplasia exists on the cervix. Our study aims at determining if the prevalence of histologically proven lesions differs by cervical four-quadrant location or by 12 o'clock surface locations of diagnosis. Methods We conducted a retrospective, histopathological study of 19 different population based cervical cancer screening studies from 1999 to 2010 by Cancer Hospital of Chinese Academy of Medical Sciences. The Institutional Review Board for human research subjects at CHCAMS approved all of the studies. During the colposcopy procedure, participant received either 4-quadrant biopsy or directed biopsy with/without endocervical curettage. Data of all samples were stratified by the methods of sampling. Kruskal-Wallis test was used to determine overall distribution of normal/CIN1, CIN2 and CIN3+ on the cervix. Results In total, 53,088 cervical samples were included in distribution analysis. 66.9 % samples were obtained by random biopsy, 16.1 % were by directed biopsy, and 17.0 % were by endocervical curettage. 95.9%of the biopsied samples were diagnosed as normal/CIN1, 2.0 % were CIN2, and 2.1 % were CIN3 + . CIN2 and CIN3+ were most often found in quadrants 2 and 3 (χKW2 = 46.6540, p

Background Comprehensive long-term evaluation for self-collected human papilloma virus (HPV) testing is not well established. We aimed to assess its predictive capacity from a long-term perspective compared with other cervical cancer mainstream screening methods. Methods 1997 women aged 35–45 years from Shanxi, China were screened by self-collected HPV testing, doctor-collected HPV testing, liquid based cytology, and visual inspection with acetic acid in 1999. The women were followed up in 2005, 2010, and 2014 with doctor-collected HPV testing, liquid based cytology, and visual inspection with acetic acid (except in 2014). On the basis of baseline screening results, we calculated cross-sectional and prospective clinical performance and 15-year cumulative incidence rates (CIRs) of cervical intraepithelial neoplasia grade 2 or higher (CIN2+). Findings Incident sensitivities for CIN2+ of all methods decreased with time, whereas incident specificity remained stable. Self-collected HPV testing predicted 84·2%, 53·2%, and 43·4% CIN2+ incident cases in 2005, 2010, and 2014, respectively, showing no significant difference with doctor-collected HPV testing and cytology at cutoff atypical squamous cells of undetermined significance (ASC-US), but higher than cytology (p=0·008, 0·004 and 0·008) and visual inspection with acetic acid (p=0·004, 0·003, 0·029) at cutoff low-grade squamous intraepithelial lesions at follow-up in 2005, 2010, and 2014, respectively. The difference of incident sensitivity between self-collected HPV testing and cotest was comparable until at 15-year follow-up (43·4% vs 56·6%, p=0·006). Women with baseline-positive self-collected HPV testing showed comparable CIN2+ CIRs with those women who were baseline-positive by doctor-collected HPV testing during 15-year follow-up, but higher than cytology at cutoff ASC-US (p=0·004), cotest (p Interpretation Self-collected HPV testing showed comparable longitudinal performance to doctor-collected HPV testing and cytology, indicating an alternative role in primary cervical cancer screening. Self-collected HPV with 5 year interval could be an option. Funding National Natural Science Foundation of China (81322040) and Chinese Academy of Medical Sciences Initiative for Innovative Medicine (CAMS-I2M-1-019).

Controversy remains over whether random cervical biopsies and endocervical curettage (ECC) should be used in women with positive screening but negative colposcopy. Our paper aims to determine the indications for random biopsies and ECC among these screened positive women. Three thousand two hundred thirteen women with any positive screening test result but negative colposcopy, who received random 4-quadrant biopsies, were pooled from 17 population-based cervical cancer screening studies done in China from 1999 to 2008. The detection rates of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) and CIN grade 3 or worse (CIN3+) stratified by cytology and high-risk human papillomavirus (HR-HPV) status were assessed, as well as the false negative rates for CIN2+ and CIN3+ by random biopsies without ECC. Compared with women with negative cytology and positive HR-HPV, those with atypical squamous cells of undetermined significance/low-grade squamous intraepithelial lesion (ASC-US/LSIL) and negative HR-HPV had the equivalent lower risks of CIN2+ and CIN3+, but ascending risks were observed in the groups of ASC-US/LSIL and positive HR-HPV, and atypical glandular cells/atypical squamous cells cannot exclude high-grade squamous intraepithelial lesion/high-grade squamous intraepithelial lesion or worse (AGC/ASC-H/HSIL+). If random biopsies were only taken without ECC, 9.3% of CIN2+ and 18.5% of CIN3+ would have been missed. For women with any positive screening but negative colposcopy, in areas with good cytological infrastructure, it was necessary to perform random biopsies plus ECC on those with cytological ASC-US/LSIL and positive HR-HPV, AGC, ASC-H, or HSIL+. In contrast, those with other results should be followed up.

To evaluate the trend of cervical cancer incidence and mortality rates during 1989-2008 in Chinese women, so as to inform the development of relevant policies and strategies in China.The incidence and mortality rates of cervical cancer during 1989-2008 in urban and rural areas were calculated based on the data from the National Cancer Registry Database. Age-standardized rates were calculated using the Chinese population of 1982 and World Segi's population of 1985. Joinpoint regression analysis was performed to obtain annual percentage changes (APC) so as to assess the trend of incidence and mortality rates over the period from 1989 to 2008.The crude incidence rate of cervical cancer in Chinese women increased from 3.06/10(5) in 1989-1990 to 11.87/10(5) in 2007-2008 (from 4.96/10(5) to 11.98/10(5) in urban registration areas and from 2.39/10(5) to 11.77/10(5) in rural registration areas).The crude mortality rate slightly increased from 2.19/10(5) in 1989-1990 to 3.20/10(5) in 2007-2008 (from 3.21/10(5) to 2.56/10(5) in urban registration areas and from 1.82/10(5) to 3.75/10(5) in rural registration areas). Generally, the upward trends of crude incidence rates were shown over the year 1989-2008, with an APC of 14.4% after 1997 in urban areas and 22.5% after 1999 in rural areas.After age standardization of world population, the APC of incidence rates in recent decade in urban areas remained stable, and the one in rural areas slightly decreased.Although the overall crude and world age-standardized mortality rates had no significant changes during 1989-2008, the crude mortality rates increased by 8.1% annually after 1999.The upward trends were also shown for crude and world age-standardized mortality rates in urban areas after 2001 with an APC of 7.3%.The crude mortality rates in rural areas increased by 3.9% annually during 1989-2008, but no significant change was found after age standardization.Over the last decade, the cervical cancer incidence and mortality rates ascended by year in China. It is particularly urgent to establish a comprehensive prevention and control system that combines cervical cancer screening and human papillomavirus vaccination, so as to reduce the burden of cervical cancer in Chinese women.

To estimate the cost-effectiveness of once-in-a-lifetime cervical cancer screening program and to predict the optimal modality for its operation on women living in rural and urban areas of China, based on Markov modeling and simulation.Three modalities including visual inspection with acetic acid plus Lugol's iodine (VIA/VILI), conventional Pap Smear (Pap Smear), and simple HPV DNA testing (careHPV) were hypothesized for the rural cohort, whereas other five modalities including Pap Smear, liquid-based cytology (LBC), simple HPV DNA testing (careHPV), Hybrid Capture 2 HPV DNA testing (HC2), and LBC plus HC2 (LBC + HC2) were tested for the urban cohort. A Markov model was constructed based on the factors as natural history, screening, diagnosis and treatment on cervical cancer using data related to the epidemics and the costs from rural and urban areas of the country. Long-term effectiveness and cost-effectiveness were predicted through simulation of the model.Compared to the non-screening scenario, the amount of life years saved were 277.97 - 2727.53 and 134.02 - 1446.84 years per 100 000 women, respectively, for different cohorts in rural and urban areas. The cost-effectiveness ratios were 1520.99 - 2453.74 and 3847.35 - 44 570.35 RMB per life year saved, respectively, for different cohorts in rural and urban areas. The incremental cost-effective ratio for careHPV starting from 40 years old (careHPV@40) and careHPV from 30 years old (careHPV@30) dominated other strategies for the rural cohort, while careHPV@40, careHPV@30, HC2 from 30 years old (HC2@30), and LBC + HC2 from 30 years old (LBC + HC2@30) were dominant for the urban cohort.All eight once-in-a-lifetime cervical cancer screening modalities were cost-effective based on our model. In particular, careHPV screening starting from 40 years old seemed to be the most cost-effective one for women living in both rural and urban areas.

To compare the predictive values of 5% acetic acid stain and visual inspection, human papillomavirus (HPV) Self test, ThinPrep Pap and HPV direct test in screening for cervical cancer with biopsy as gold standard. Positive predictive values and negative predictive values were compared simultaneously by joint hypothesis tests and then either positive predictive values or negative predictive values of the any two screening tests were compared by marginal regression based on both GEE and weighted least square methods. Hochberg method was used for multiplicity adjustment. It was showed that HPV direct test had the highest negative predictive value and ThinPrep Pap the highest positive predictive value. 5% acetic acid stain and visual inspection had both the lowest positive predictive value and negative predictive value. Both HPV direct test and ThinPrep Pap were efficient, but the latter required compatible infrastructure and skilled caregivers to go with. Both 5% acetic acid stain and visual inspection were inexpensive, and their positive predictive value and negative predictive value were lower than HPV self-test. They also had similar positive predictive value with HPV direct test and similar negative predictive value with ThinPrep Pap. HPV self-test appeared to be efficient, suggesting that it had significant potential for screening program to be implemented in the rural areas of China since the test could be performed without speculum examination in low-resource regions.

To analyze the incidence and mortality of oral and pharyngeal cancers from 32 cancer registration centers, 2003 to 2007.Data from 32 eligible cancer registries were included in this study. Both crude and age-standardized incidence and mortality of oral and pharyngeal cancers from 2003 to 2007 were calculated and stratified by area and gender. Age-stratified incidence and mortality, as well as the proportions of new and death cases of oral and pharyngeal cancer were also calculated at each site.Mouth, tongue and salivary gland were the most predilection sites of oral and pharyngeal cancers. The crude incidence for both oral and pharyngeal cancers was 3.15/10(5) from 2003 to 2007. The age-standardized incidence rates using the Chinese population (1982) and the World Segi's population were 1.75/10(5) and 2.26/10(5). The crude mortality of oral and pharyngeal cancer was 1.37/10(5) from 2003 to 2007; with age-standardized mortality rates, using the Chinese population (1982) and the World Segi's population were 0.69/10(5) and 0.94/10(5). Both incidence and mortality were higher in males than in females, higher in urban than in rural areas, and ascended with age. Age-standardized incidence and mortality in Zhongshan city ranked first among all the cancer registration areas. Age-standardized incidences by gender and area increased slightly from 2003 to 2007, while age-standardized mortalities were stable.Although the incidence and mortality of oral and pharyngeal cancer were low in China from 2003 to 2007, attention should also be paid since the exposure of relative risk factors did not seem to have reduced and the incidence increased slightly.

To explore the appropriate strategies which are suitable for the areas with diverse health and economic resource settings in China by estimating the life outcomes and cost-effectiveness of several cervical cancer screening strategies.Markov model was used to calculate the long-term effectiveness, utility, benefit and cost among screened and unscreened cohorts in rural and urban areas, and then analyses of cost-effectiveness, cost-utility and cost-benefit were performed. The assessed screening strategies were acetic acid of visual inspection combined with Lugol's iodine staining (VIA/VILI), conventional Pap smear and simple HPV DNA testing (careHPV) in rural areas, and conventional Pap smear, simple HPV DNA testing (careHPV), HPV DNA testing (HC2) and liquid-based cytology (LBC) alone or combined with HPV DNA testing (LBC+HC2) in urban areas. We estimated the life outcomes and cost-effectiveness of the above screening strategies at one-year, 3-year and 5-year intervals.All of the screening strategies were effective to decrease cervical cancer mortality and to increase life years, with a trend of shorter screening interval having better effectiveness. However, no matter in urban or rural areas, compared with careHPV testing at 5-year interval, the costs of other screening strategies were 1.28 - 13.86 folds, 1.31 - 14.14 folds, and 1.27 - 12.80 folds higher to avoid one death, to save a year of life, and a QALY, and the benefit per cost of other screening strategies was 9.9%-90.2%.careHPV testing at 5-year interval has the best cost-effectiveness performance and the highest benefit-cost ratio with the moderate life outcomes. It is the optimal cervical cancer screening strategy to be generalized in our country. careHPV testing at 3 years interval can be considered in more developed areas to achieve better effectiveness.

Liquid-based cytology (LBC) has been widely used for cervical cancer screening. Despite numerous studies and systematic reviews, to the authors' knowledge few large studies to date have focused on biopsy-confirmed cervical lesions and controversy remains concerning its diagnostic accuracy. The objective of the current study was to assess LBC for detecting biopsy-confirmed cervical intraepithelial neoplasia (CIN) and cancer.A pooled analysis of LBC using data from 13 population-based, cross-sectional, cervical cancer screening studies performed in China from 1999 to 2008 was performed. Participants (n = 26,782) received LBC and human papillomavirus testing. Women found to be positive on screening were referred for colposcopy and biopsy. The accuracy of LBC for detecting biopsy-confirmed CIN of type 2 or worse (CIN2+) as well as CIN type 3 or worse (CIN3+) lesions was analyzed.Of 25,830 women included in the analysis, CIN2+ was found in 107 of 2612 with atypical squamous cells (4.1%), 142 of 923 with low-grade squamous intraepithelial neoplasia (15.4%), 512 of 784 with high-grade squamous intraepithelial neoplasia (65.3%), 29 of 30 with squamous cell carcinoma (96.7%), 4 of 27 with atypical glandular cells (14.8%), and 85 of 21,454 with normal cytology results (0.4%). No invasive cancers were found to have atypical squamous cells, atypical glandular cells, or cytologically normal slides. The overall sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of LBC for detecting CIN2+ were 81.0%, 95.4%, 38.3%, 99.3 %, and 94.9%, respectively. Although Hybrid Capture 2 was more sensitive than LBC, the specificity, positive predictive value, and overall accuracy of LBC were higher than those of Hybrid Capture2 at 85.2%, 18.6%, and 85.5%, respectively.The results of the current study indicate that the performance of LBC can effectively predict the risk of existing CIN2+ and may be a good screening tool for cervical cancer prevention in a developing country.

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 $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.

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.

The study was embedded in Shanxi Province Cervical Cancer Screening Study II with the aim of examining the association between history of diagnosed tuberculosis or cervical inflammation and oncogenic human papillomavirus (HPV) infection, persistent oncogenic HPV infection, cervical intraepithelial neoplasia grade 3 or cervical cancer (CIN3+) in an isolated rural population of China. A total of 8,798 women were recruited for cervical cancer screening and an interviewer-administered questionnaire. Of the women in the study, 2.7% and 34% reported a diagnosis of tuberculosis and cervical inflammation, respectively. In the model for HPV infection, HPV persistence and CIN3+, we show an increasing magnitude of effect of tuberculosis with increasing severity of disease, as demonstrated by the increasing odds ratios from 1.68 for HPV positivity, to 1.75 for persistent HPV and then 2.08 for CIN3+. Women reporting a diagnosis of tuberculosis, cervical inflammation or both tuberculosis and cervical inflammation were at 75%, 22% and 113% higher odds of persistent HPV infection, respectively. One percent of the study population was diagnosed with tuberculosis and cervical inflammation, placing them at 90% and 113% higher odds of infection with HPV and persistent HPV, respectively. Tuberculosis and oncogenic HPV are identified for the first time as co-infections in rural unscreened women in Shanxi Province, China, highlighting the importance of infection history in assessing an individual' s risk for HPV infection, persistence and CIN3+.

BACKGROUND: 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. METHODS: Eligible women ages 30 to 49 years were recruited for this cross-sectional population-based study in rural China. Women were assessed by visual inspection with acetic acid (VIA), LBC, and high-risk HPV HC2 DNA assay. Cervical specimens were preserved according to SurePath or ThinPrep protocols. LBC results were manually read. HC2 testing was performed on specimens with sufficient residual volume. Colposcopies and biopsies were performed on women who were VIA positive at the time of initial screening. Women with abnormal LBC or HC2 test results were called back for colposcopies and 4-quadrant cervical biopsies. RESULTS: Of 2005 eligible women, 972 were tested by SurePath and 1033 by ThinPrep. Compared with SurePath samples, ThinPrep samples had higher rates of unsatisfactory cytology (0.2% for SurePath and 1.5% for ThinPrep) and insufficient residual volume for HC2 (0.0% for SurePath and 18.2% for ThinPrep). SurePath samples yielded higher sensitivities and similar specificities for LBC and HC2 testing of residual specimens, but these differences were not determined to be significant by area-under-the-curve analysis (LBC performance: 0.89 for SurePath and 0.85 for ThinPrep; HC2 performance: 0.91 for SurePath and 0.89 for ThinPrep). CONCLUSIONS: Both methods yielded similar validity in detecting significant cervical lesions. However, SurePath samples yielded higher rates of satisfactory LBC slides and sufficient residual volume for HC2. Cancer (Cancer Cytopathol) 2011;000:000–000. V C 2011 American Cancer Society.

Few 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. A 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. Within 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. Our 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.

To assess the feasibility and accuracy of different cervical cancer screening algorithms suitable for different regions, and promote the prevention and control of cervical cancer in China.Using the data of a cross-sectional comparative trial of multiple techniques to detect cervical intraepithelial neoplasia in Xiangyuan County, Shanxi Province, conducted in 1999, to evaluate the feasibility and accuracy of different cervical cancer screening algorithms. All the women were screened by six screening tests, including liquid based cytology (LBC), fluorescence spectroscopy, visual inspection with 5% acetic acid staining (VIA), colposcopy, self-sampled HPV DNA and clinician-sampled HPV DNA test, and each woman had histopathological diagnosis. Different screening algorithms were developed by combining the screening tests in parallel or in serial, and the performance indexes of the algorithms such as sensitivity, specificity, colposcopy referral rate and receiver operating characteristic (ROC) curve for detecting the high grade lesions (or= CIN 2) were compared.Among the algorithms combined by LBC and HPV DNA testing, for the combination in parallel (either cytology was greater than ASC-US or HPV positives), its sensitivity was 100%, specificity was 68.6%, and colposcopy referral rate was 34.4%; for the algorithm of LBC as primary screening test, with ASC-US women triage by HPV DNA testing, its sensitivity was 93.0%, specificity was 89.9%, and colposcopy referral rate was 13.7%; for the algorithm of HPV DNA testing as the primary screening test, with HPV positive women triage by LBC, its sensitivity was 91.7%, specificity was 93.0%, and colposcopy referral rate was 10.6%. ROC analysis showed that LBC primary testing followed by HPV triage and HPV primary testing followed by LBC triage were much better than the combination in parallel (P = 0.0003, P = 0.0002). Among the algorithms with LBC or HPV DNA testing solely as primary screening test, the sensitivity, specificity and colposcopy referral rate of LBC were 94.2%, 77.3%, 25.7% and 87.2%, 93.5%, 10.0%, respectively, for cutoff by ASC-US or by LSIL; the sensitivity, specificity and colposcopy referral rate of HPV DNA testing were 97.6%, 84.8%, 18.8% and 83.5%, 85.9%, 17.1%, respectively, for clinician-sampled and self-sampled. Clinician-sampled HPV DNA testing was better than LBC cutoff by ASC-US or self-sampled HPV DNA testing (P = 0.005, P = 0.002). Among the algorithms combined by VIA and HPV DNA testing, the sensitivity, specificity and colposcopy referral rate were 70.9%, 74.3% and 27.6% for VIA alone as primary screening test; the sensitivity, specificity and colposcopy referral rate were 65.9%, 95.2% and 7.4% for HPV as primary screening test with HPV positive women triage by VIA. HPV primary testing followed by VIA triage was better than VIA alone (P = 0.004).Considering the health-resource settings and women's preference, both HPV primary testing followed by LBC triage and LBC primary testing followed by HPV triage are suitable for developed regions, moderately developed regions may choose either LBC or HPV as the screening approach, VIA is a suitable primary screening test in less developed regions, and HPV primary testing followed by VIA triage will be more effective if low cost HPV test is available in the future.

To analyze the cervical cancer mortality and distribution profiles by areas and population in 2004 - 2005 and the changes in the last 30 years.The demographic information and cervical cancer death data came from the Third National Retrospective Sampling Survey of Death Causes which including 158 sampling areas (including 61 cities and 97 villages; 52 in the east region, 49 in the middle region and 57 in the west region) covered 31 province-level regions in the interior of China by multiple stage stratified clustering sampling. The total number of the samples were 142 660 482 person years (72 970 241 person years in male and 69 690 241 person years in female). The crude and age-specific death rate was calculated. The standardized death rate was calculated by using 5 years interval from the census data of 2000. In addition, the mortality data was compared with the two previous national death surveys in 1970's and 1990's, respectively.In the sampling region of the third retrospective death causes survey from 2004 to 2005, the crude death rate of cervical cancer was 2.86/100 000 (1995/69 690 241), which accounting for 2.86% (1995/69 667) and ranking 9th of all cancer death causes in female population. The crude death rates of cervical cancer were 2.88/100 000 (1326/46 091 419) and 2.83/100 000 (669/23 598 822) for rural areas and urban areas, respectively, the Chinese population adjusted death rates of rural and urban areas were 2.01/100 000 and 1.67/100 000, respectively. The standardized death rates of cervical cancer in 1973 - 1975 and 1990 - 1992 were 11.10/100 000 and 3.25/100 000, respectively, which accounting for 17.91% and 4.86%, respectively; in 2004 - 2005, the crude death rates increased by age, rose remarkably from the age of 40 and arrived the peak of 20.83/100 000 (82/393 624) at the age of 85. The mortality among 35 - 44 year-old group was higher than those in 1990's. The crude death rates of the middle, west and east areas were 3.41/100 000 (827/24 225 738), 3.25/100 000 (636/19 563 647) and 2.05/100 000 (532/25 900 856), respectively, the Chinese population adjusted death rates of the middle and west areas were about twice that of the east (2.35/100 000 in the middle, 2.38/100 000 in the west, and 1.19/100 000 in the east).The mortality of cervical cancer was higher in rural areas than that in urban, as well as higher in the middle and west areas than that in east area in the interior of China in 2004 - 2005. Younger trend of cervical cancer death was observed; the mortality of cervical cancer and constituent ratio in the female tumor death continued to decline compared to those in 1973 - 1975 and 1990 - 1992.

To determine why a vaginal self-collection tested for high-risk human papillomavirus (HR-HPV) by Hybrid Capture 2(R) (hc2) has lower sensitivity and specificity for cervical intraepithelial neoplasia Grade 2 or worse (or = 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(R), (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 withor = 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 withor = CIN 2 and negative self-collected hc2 tests were positive for HR-HPV by LA. Of 2,578 women withoutor = 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 withoutor = 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 withor = CIN 2.

Background and objective In China, there has been no established national program for cervical cancer prevention, the screening methods and experiences are especially deficient in the rural areas. The aim of this paper is to evaluate the effects of acetic acid/Lugol's iodine (VIA/VILI) used for screening of cervical cancer and pre-cancerous lesions in a rural area of China by analyzing the large-scale population-based screening data from the demonstration site. Methods Women aged 30-59 years from Xiangyuan County in Shanxi Province were recruited for cervical cancer screening from 2005 to 2007. VIA/VILI was the primary screening method followed by colposcopy if the VIA/VILI was positive. Cervical lesions were diagnosed by directed biopsy under the colposcopy. The VIA/VILI negative women or cervical intraepithelial neoplasia 1 (CIN1) were re-screened using the same procedure in the next year. Results In total, 7145 women received the cervical cancer screening, with a participation rate of 74.75%. Their average age was 42.16 years. A total of 1287 women were consecutively screened for three times from 2005 to 2007. The detection rates of CIN2, CIN3 and cervical cancer were 0.70% (9/1287), 1.01% (13/1287) and 0.23% (3/1287) for the first round screening, and were 0.22% (2/976), 0.11% (1/976) and 0% (0/976) for the second round screening, respectively. Only one CIN2 was found in the third round screening. In the years of 2006-2007, 3490 women were screened consecutively twice. The detection rates of CIN2, CIN3 and cervical cancer were 0.26% (9/3490), 0.52% (18/3490) and 0.15% (5/3490) for the first round screening, and 0.40% (14/2943), 0.40% (14/2943) and 0.03% (1/2943) for the second round screening. Likewise, 2 368 women were screened consecutively twice in the years of 2007-2008. The detection rates of CIN2, CIN3 and cervical cancer were 0.55% (13/2368), 0.25% (6/2368) and 0.12% (3/2368) for the first round screening, and 0.42 (10/2040), 0.04% (1/2040) and 0% for the second round screening. The cumulative detection rates for CIN2, CIN3 and cervical cancer were 0.81% (58/7145), 0.74% (53/7145) and 0.17% (12/7145), respectively. And 53.45% (31/58) of CIN2, 68.81% (37/53) of CIN3 and almost all cervical cancers (11/12) were found during the first round screening, except for an early stage cervical cancer (Ia). Only one CIN2 was detected in the third round screening in the same population. The average age of CIN1, CIN2, CIN3 and cervical cancer were 38.65, 40.61, 44.10 and 46.73 years, respectively. Conclusions VIA/VILI can be used as an alternative screening method for cervical cancer and high-grade pre-cancerous lesions among the women aged 30-59 years in China's rural areas because of its low cost, easy training for the local health providers, and less depending on facilities. One round screening by VIA/VILI can detect more than a half of CIN2, two-thirds of CIN3 and almost all the cervical cancer in the population, and the detection rates of CIN2/3 can be increased by two consecutive rounds of screening.

To determine the association between viral load of high risk human papillomavirus (HR-HPV) and cervical intraepithelial neoplasia (CIN).Cervical exfoliated cells were collected from 18 186 women aged 17 -59 from six urban areas and eight rural areas when they were screened in the cross-sectional population-based studies from 1999 to 2008. HR-HPV was detected by the Hybrid Capture 2 (hc2) system, and viral load was measured by the ratio of relative light units to standard positive control (RLU/PC). RLU/PC was categorized for analysis into four groups: negative [0, 1.00), low viral load [1.0, 10.00), moderate viral load [10.00, 100.00), and high viral loador = 100.00. Cervical lesions were diagnosed by biopsies as normal, CIN 1, CIN 2, CIN 3 and squamous cervical cancer (SCC). Association between HR-HPV viral load and CIN was evaluated by unconditional multinomial logistic regression.The HR-HPV infection rate of the population was 14.51% (2515/17334). 100.00% (29/29) of SCC, 97.63% (206/211) of CIN 3, 93.43% (199/213) of CIN 2, 75.04% (421/561) of CIN 1 and 10.17% (1660/16320) of normal women were positive for HR-HPV DNA. The median RLUs for the HR-HPV positive women with SCC, CIN 3, CIN 2, CIN 1 and normal were 320.85, 158.05, 143.70, 125.34 and 9.64, respectively. There were significant differences among the distributions of viral loads in each lesion (chi2 = 6190.40, P0.01). The severity of CIN increased with the viral load (chi2 = 5493.35, P0.01). Compared with the risks of CINs in HR-HPV negative population, the risks of CINs in low, moderate and high viral loads were increased gradually [OR(95% CI) : CIN 1 : 9.01(6.31 - 12.87), 24.96(18.23 - 34.17) and 68.42(51.40 - 91.08); CIN 2 : 26.44(12.07 - 57.95), 98.53(49.54 - 195.98) and 322.88(168.62 - 618.27); CIN 3+ : 72.89(24.02-221.18); 343.58(121.81-969.09) and999.99(473.38 -999.99)], and there were obvious dose-response relationships (chi2trend was 3115.05, 2413.95 and 3098.57, respectively. P0.01). In each age group of the HR-HPV positive population,the risks of CIN 2 + in the women with moderate or high viral load were higher than the one with low viral load [OR(95% CI):35 : 4.71(1.23 - 18.09) and 15.06(4.40 - 51.49); 35 -: 4.01 (1.62 -9.90) and 14.09(6.15 -32.28); 40 - : 3.06(1.52 -6.16) and 7.78(4.05 -14.95);or =45: 3.50(1.36 -9. 01) and 7.57(3.13 - 18. 30)], and there was a positive correlation between the risk of CIN 2+ and the viral load (chi2trend was 51.33, 66.28, 53.64 and 51.00, respectively. P0.01). The risk of CIN 2 + was highest among the women aged 40 - with high viral load [OR (95% CI) : 2.02 (1.15 - 3.52)].There is strong correlation between the HR-HPV viral load and the severity of CIN, and so is the correlation between the HR-HPV viral load and the risk of CIN 2 +. A moderate to high viral load of HR-HPV should be the major risk factor for the cervical cancer and CIN 2 and CIN 3, and there is a higher risk in the women aged 35 or older than the younger ones. Considering both the age and viral load could help the doctors to manage the screening women more effectively.

showed no meaningful change in median dynamic parameters but did have a significant reduction in viable fraction. Analyzable diffusion data were available for 51/61 patients; 16 patients demonstrated a greater than 30% on-treatment increase in ADC. 15 of these patients were dosed at 30mg/kg. Conclusions: Reduction in median dynamic parameters reflective of vessel permeability and perfusion was observed in 62% of patients. On the Q2W schedule, sustained decrease across all time-points was only observed at 30mg/kg. Increase in ADC was primarily observed in patients treated at 30mg/kg. The DCE-MRI and DW-MRI findings of ontreatment decrease in tumor vessel permeability, perfusion and cellular density support the proposed anti-angiogenic mechanism of action of Vanucizumab.

Background Human 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. Methods Population-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. Results A 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 = 4 partners versus 1 partner, P Conclusions HPV 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.

Background Human papillomavirus (HPV) 16 and 18 are the two most common HPV oncogenic types that can be prevented by vaccination. This study aimed at assessing the cost-effectiveness of 3 doses of the bivalent HPV vaccine in rural and urban settings in China. Methods A Markov model was adapted to reflect the lifetime of a modelled 100,000 12-year-old girls cohort in rural and urban settings in China. Input parameters were obtained from published literature, official reports and a two-round expert review panel. Clinical and economic outcomes of vaccination at age 12 with screening was compared to screening only. In the base case analysis, a 3 % discount rate, the vaccine cost of 247 CNY (US$ 39, PAHO vaccine cost in 2013), two rounds of screening in a life time and 70 % coverage for both screening and vaccination were used. One-way, two-way and probabilistic sensitivity analyses were performed. We used different thresholds of cost-effectiveness to reflect the diversity of economic development in China. Results Vaccination in addition to screening could prevent 60 % more cervical cancer cases and deaths than screening only. The incremental cost effectiveness ratio varied largely when changing cost of vaccination and discount in one way analysis. Vaccination was very cost-effective when the vaccine cost ranged 87-630 CNY (US$ 13.8-100) in rural and 87-750 CNY (US$ 13.8–119) in urban; and remained cost-effective when the vaccine cost ranged 630–1,700 CNY (US$ 100–270) in rural and 750–1,900 CNY (US$ 119–302) in urban in two way analysis. Probabilistic sensitivity analyses showed that model results were robust. Conclusions In both rural and urban, the vaccination cost and discounting are important factors determining the cost-effectiveness of HPV vaccination; policy makers in China should take these into account when making a decision on the introduction of HPV vaccine. In areas with a high burden of cervical cancer and limited screening activities, HPV vaccination should be prioritized. However, the vaccine cost needs to be reduced in order to make it very cost-effective and affordable as well, in particular in poverty areas with high disease burden. Electronic supplementary material The online version of this article (doi:10.1186/s12885-016-2893-x) contains supplementary material, which is available to authorized users.

Input data values for base case, one-way sensitivity analyses and probabilistic sensitivity analyses. a Screening practice: all women screened twice lifetime at 35 years and 45 years. Health states No HPV, HPV, CIN 1 and CIN 2/3 have utility=1 (i.e., no disutility); health states death and death from cervical cancer have utility=0; PSA=probabilistic sensitivity analyses; CIN=cervical intraepithelial neoplasia; HPV=human papillomavirus; CC=cervical cancer; VIA/VILI=visual inspection with acetic acid/iodine; NA=Not include in probabilistic sensitivity analyses; Se=sensitivity. (DOCX 21 kb)

Input data values for base case, one-way sensitivity analyses and probabilistic sensitivity analyses. a Screening practice: all women screened twice lifetime at 35 years and 45 years. Health states No HPV, HPV, CIN 1 and CIN 2/3 have utility=1 (i.e., no disutility); health states death and death from cervical cancer have utility=0; PSA=probabilistic sensitivity analyses; CIN=cervical intraepithelial neoplasia; HPV=human papillomavirus; CC=cervical cancer; VIA/VILI=visual inspection with acetic acid/iodine; NA=Not include in probabilistic sensitivity analyses; Se=sensitivity. (DOCX 21 kb)