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Thermal ablation is a point-of-care ablative treatment technique for cervical intraepithelial neoplasia (CIN). However, limited information is available about its efficacy in low- and middle-income countries. We evaluated the efficacy of thermal ablation in treatment of CIN detected through high-risk human papillomavirus (HPV) screening in China. Women positive on high-risk HPV and having colposcopically suspected lesions eligible for ablation underwent colposcopy, biopsy and thermal ablation in one visit. Women ineligible were recalled for large loop excision of transformation zone (LLETZ) when histopathology results were high-grade CIN. Posttreatment follow-up at 6 months or more was with HPV test and cytology followed by colposcopy and biopsy for HPV and/or cytology-positive women. Cure was defined as either negative cytology and HPV test or absence of histopathology proved CIN in any positive women. Of total 218 HPV-positive women treated with thermal ablation (n = 170) or LLETZ (n = 48), 196 reported for follow-up evaluation. For women with histologically confirmed CIN at baseline (thermal ablation-104; LLETZ-38), cure rates were 84.6% for thermal ablation and 86.8% for LLETZ. Cure rates after thermal ablation were 90.3% for CIN grade one (CIN1) and 76.2% for CIN grade two or worse (CIN2+). HPV clearance rate was 80.4% in women undergoing thermal ablation, which was lower for HPV16/18 compared to other oncogenic types (67.6% vs 85.7%). HPV test had a negative predictive value (NPV) of 98.7% to detect CIN2+ at follow-up and the positive predictive value (PPV) was 40.4%. Thermal ablation is effective to treat CIN as well as to clear the high-risk HPV infection. HPV test has high PPV and NPV in following up patients posttreatment.

Objective To estimate long-term outcomes of biopsy-confirmed cervical intraepithelial neoplasia grade 1 (CIN1) or normal cervix and identify the cofactors during disease progression. Methods In 1999, a cervical cancer screening cohort in Shanxi, China, enrolled 1997 women aged 35–45. They were followed up at year 6, 11, and 15 after enrollment with high-risk human papillomavirus (hrHPV) DNA testing, liquid-based cytology, and visual inspection with acetic acid. Progression, persistence, and regression rates were calculated, stratified by baseline hrHPV and cytological status. Risk factors associated with hrHPV acquisition, persistence, and progression were examined. Results The cumulative rates of progression to CIN2+ among CIN1 over 6, 11, and 15 years were 7.5%, 21.4%, and 24.0%, respectively; the regression rates to normal cervix were 85.0%, 76.7%, and 72.9%, respectively. Over 6, 11, and 15 years, 0.7%, 2.9%, and 5.2% of normal cervix developed CIN2+, respectively, but over 90% remained normal after 15 years. CIN1 or normal cervix positive for hrHPV had significantly higher progression rates to CIN2+ than those without hrHPV. Similarly, the severity of cytological status was found to be associated with an increased risk of developing CIN2+. Women who had an earlier sexual debut were at a higher risk of acquiring new HPV infection and repeated HPV infections. Conclusions Clinical follow-up strategies for women with CIN1 or normal cervix could be adjusted accordingly based on hrHPV/cytology status.

Human papillomavirus (HPV) test, self-sampling and thermal ablation for cervical intraepithelial neoplasia (CIN) have been developed separately to increase screening coverage and treatment compliance of cervical cancer screening programmes. A large-scale study in rural China screened 9,526 women with their combinations to explore the optimal cervical cancer-screening cascade in the real-world. Participants received careHPV and polymerase chain reaction (PCR) HPV tests on self-collected samples. Women positive on either HPV test underwent colposcopy, biopsy and thermal ablation in a single visit. Samples positive on either HPV test were retested for genotyping. Absolute and relative performance of HPV tests, triage strategies, 'colposcopy and thermal ablation' approach were statistically evaluated. PCR HPV test detected 33.3% more CIN grade two or worse (CIN2+) at a cost of 28.1% more colposcopies compared to careHPV. Sensitivities of PCR HPV and careHPV tests to detect CIN2+ were 96.7 and 72.5%. Specificities for the same disease outcome were 82.1 and 86.0%. Triaging HPV-positive women with HPV16/18 genotyping considerably improved the positive predictive value for CIN2+ (4.8-5.0 to 18.2-19.2%). Ninety-six women positive on HPV and having abnormal colposcopy were eligible for thermal ablation and all accepted same-day treatment, contributing to 64.6% being treated appropriately (CIN1+ on histopathology), which reached up to 84.8% among women positive on HPV 16/18 triage. No serious side-effects/complications were reported. The combination of PCR HPV test followed by HPV 16/18 triaging on self-collected samples and colposcopy of triage positive women followed by immediate thermal ablation might be the appropriate screening cascade for rural China.

Background Cervical cancer is a major public health concern in China. We report the end‐of‐study results of a phase II/III trial to assess the efficacy, immunogenicity, and safety of the AS04‐human papillomavirus (HPV)‐16/18 vaccine in Chinese women aged 18‐25 years followed for up to 72 months after first vaccination. Results of approximately 57 months following first vaccination have been previously reported. Methods Healthy 18‐25‐year‐old women (N = 6051) were randomized (1:1) to receive three doses of AS04‐HPV‐16/18 vaccine or Al(OH)3 (control) at Months 0‐1‐6. Vaccine efficacy against HPV‐16/18 infection and cervical intraepithelial neoplasia (CIN), cross‐protective vaccine efficacy against infections and lesions associated with nonvaccine oncogenic HPV types, immunogenicity, and safety were assessed. Efficacy was assessed in the according‐to‐protocol efficacy (ATP‐E) cohort (vaccine N = 2888; control N = 2892), total vaccinated cohort for efficacy (TVC‐E; vaccine N = 2987; control N = 2985) and TVC‐naïve (vaccine N = 1660; control N = 1587). Results In initially HPV‐16/18 seronegative/DNA‐negative women, vaccine efficacy against HPV‐16/18‐associated CIN grade 2 or worse was 87.3% (95% CI: 5.5, 99.7) in the ATP‐E, 88.7% (95% CI: 18.5, 99.7) in the TVC‐E, and 100% (95% CI: 17.9, 100) in the TVC‐naïve. Cross‐protective efficacy against incident infection with HPV‐31, HPV‐33 and HPV‐45 was 59.6% (95% CI: 39.4, 73.5), 42.7% (95% CI: 15.6, 61.6), and 54.8% (95% CI: 19.3, 75.6), respectively (ATP‐E). At Month 72, >95% of initially seronegative women who received HPV vaccine in the ATP cohort for immunogenicity (N = 664) remained seropositive for anti‐HPV‐16/18 antibodies; anti‐HPV‐16 and anti‐HPV‐18 geometric mean titers were 678.1 EU/mL (95% CI: 552.9, 831.5) and 343.7 EU/mL (95% CI: 291.9, 404.8), respectively. Serious adverse events were infrequent (1.9% vaccine group [N = 3026]; 2.7% control group [N = 3025]). Three and zero women died in the control group and the vaccine group respectively. New onset autoimmune disease was reported in two women in the vaccine group and two in the control group. Conclusions This is the first large‐scale randomized clinical trial of HPV vaccination in China. High and sustained vaccine efficacy against HPV‐16/18‐associated infection and cervical lesions was demonstrated up to Month 72. The vaccine had an acceptable safety profile. Combined with screening, prophylactic HPV vaccination could potentially reduce the high burden of HPV infection and cervical cancer in China. Trial registration NCT00779766., Cervical cancer is one of the most aggressive forms of cancer that women can suffer from. The presence of human papillomavirus (HPV) is responsible for almost all cases of cervical cancer. For these reasons, the world health organization recommends that HPV vaccines should be included in national vaccination programs. From the first licensure of the first HPV vaccine in 2006 to the development of new HPV vaccines, the latter have been studied in clinical trials and demonstrated to decrease in the number of cervical cancers while remaining acceptably safe. Many developed countries have included HPV vaccination in their program. These countries reported a decrease of cervical cancer cases. Many countries from the less developed regions are still yet to introduce HPV vaccination. The novelty: In 2016, the Chinese authorities approved licensure of the first HPV vaccine for use in China to help prevent cervical cancer and based their decision on clinical trials conducted in China. We present here the final results of the key clinical trial of this HPV vaccine that involved around 6000 Chinese women over 6 years. The impact: Chinese women represent almost 10% of the worldwide population at risk of cervical cancer. Latest estimations from 2016 indicate that 111 000 new cervical cancer cases are reported every year in China. This number could be reduced with the HPV vaccination.

To evaluate whether low-frequency ultrasound-facilitated transdermal delivery of a Chinese medicine (CM) formula could improve the efficacy of intrapleural administration of interleukin-2 (IL-2) in treatment of malignant pleural effusion (MPE). A total of 110 eligible participants were randomized into the low-frequency sonophoresis (LFS) of CM (LSF/CM) group (55 cases) and the control group (55 cases) by simple randomization using a random number table. The control group was treated with an intrapleural administration of IL-2; and the LFS/CM group was treated with LFS of a CM gel formulation, combined with the same IL-2 injection as in the control group. The CM formula consisted of Semen Lepidii, Semen Sinapis, Ramulus Cinnamomi, Poriacocos, Herba Lycopi, and Radix Paeoniae Rubra. After 2-week treatment, the therapeutic outcome was determined by the change of the amount of MPE, which was evaluated by B-scan ultrasound and/or chest X-ray, and the change of quality of life (QOL) scores, which were evaluated by the Eastern Cooperative Oncology Group (ECOG) performance status. A significantly higher objective remission rate (ORR) was obtained with intrapleural IL-2 plus LFS/CM than IL-2 treatment alone (P=0.049). In addition, more patients in the LFS/CM group than in the control group had an improved QOL score (P=0.048), and no patients in the LFS/CM group had a reduced QOL. Conclusion: LFS of CM formulation could effectively alleviate MPE and improve the QOL of cancer patients.

To evaluate the efficacy and safety of topical delivery of modified Da-Cheng- Qi Decoction (加味大承气汤, MDCQD) by low-frequency ultrasound sonophoresis (LFUS) in patients with refractory metastatic malignant bowel obstruction (MBO) using an objective performance criteria (OPC) design. Fifty patients with refractory metastatic MBO were enrolled in this open-label single-arm clinical trial. Alongside fasting, gastrointestinal decompression, glycerol enema, intravenous nutrition and antisecretory therapy, a 50 g dose of MDCQD (prepared as a hydrogel) was applied through topical delivery at the site of abodminal pain or Tianshu (S 25) using LFUS for 30 min, twice daily for 5 consecutive days. The overall outcome was the remission of intestinal obstruction, and improvement on abdominal pain, abdominal distention, nausea and vomiting scores. Indicators of safety evaluation included liver and renal function as well as blood coagulation indicators. Among 50 patients, 5 patients (10%) showed complete remission of intestinal obstruction and 21 patients (42%) showed improvement of intestinal obstruction. The overall remission rate of bowel obstruction was 52%. The results of the symptom score, based on the severity and frequency of the episode, are as follows: 26 patients (52%) showed improvment on symptom scores, 20 patients (40%) did not respond to treatment, and 4 patients (8%) discontinued treatment due to intolerance. No serious adverse effects or abnormal changes on liver and renal function or blood coagulation were observed. Topical delivery of MDCQD at 100 g/day using LFUS can improve the treatment response in patients with refractory metastatic MBO.

Objective Precise prevention is more desired for cervical cancer due to the huge population, high prevalence of human papillomavirus (HPV) infection in China and the vision of screen-and-treat strategies in low- and middle-income countries (LMICs). Considerations of combining type-specific prevalence and attribution proportion to high-grade cervical intraepithelial neoplasia are informative to more precise and effective region-specific cervical cancer prevention and control programs. The aim of the current study was to determine the genotype distribution of HPV and attribution to cervical precancerous lesions among women from rural areas in North China. Methods A total of 9,526 women participated in the cervical cancer screening project in rural China. The samples of women who tested positive for HPV were retested with a polymerase chain reaction (PCR)-based HPV genotyping test. The attribution proportion of specific high-risk human papillomavirus (HR-HPV) types for different grades of cervical lesions was calculated by using the type contribution weighting method. Results A total of 22.2% (2,112/9,526) of women were HR-HPV positive and HPV52 (21.7%) was the most common HR-HPV genotype, followed by HPV58 (18.2%), HPV53 (18.2%) and HPV16 (16.2%). The top three genotypes detected in HR-HPV-positive cervical intraepithelial neoplasia (CIN)1 were HPV16 (36.7%), HPV58 (20.4%), HPV56 (15.3%). Among CIN2+, the most frequent genotypes were HPV16 (75.6%), HPV52 (17.8%), HPV58 (16.7%). HPV16, 56, 58, 53, 52, 59, 68, and 18 combined were attributed to 84.17% of all CIN1 lesions, and HPV16, 58, and 52 combined were attributed to 86.98% of all CIN2+ lesions. Conclusions The prevalence of HR-HPV infection among women from rural areas in North China was high and HPV16, HPV58, HPV52 had paramount attributable fraction in CIN2+. Type-specific HPV prevalence and attribution proportion to cervical precancerous lesions should be taken into consideration in the development of vaccines and strategy for screening in this population.

Background The World Health Assembly has adopted a global strategy to eliminate cervical cancer. However, neither the optimal pathway nor the corresponding economic and health benefits have been evaluated. We take China as an example to assess the optimal pathway towards elimination and the cost-effectiveness of tailored actions. Methods A validated hybrid model was used to assess the costs and benefits of alternative strategies combining human papillomavirus vaccination, cervical screening, and treatment of pre-invasive lesions and invasive cancer for females with different immunization history. All Chinese females living or projected to be born during 2015–2100, under projected trends in aging, urbanization, and sexual activity, were considered. Optimal strategies were determined by cost-effectiveness efficiency frontiers. Primary outcomes were cervical cancer cases and deaths averted and incremental cost-effectiveness ratios (ICERs). We employed a lifetime horizon from a societal perspective. One-way and probabilistic sensitivity analyses evaluate model uncertainty. Results The optimal pathway represents an integration of multiple tailored strategies from females with different immunization history. If China adopts the optimal pathway, the age-standardized incidence of cervical cancer is predicted to decrease to fewer than four new cases per 100,000 women (i.e., elimination) by 2047 (95% confidence interval 2043 to 2050). Compared to the status quo, the optimal pathway would avert a total of 7,509,192 (6,922,744 to 8,359,074) cervical cancer cases and 2,529,873 (2,366,826 to 2,802,604) cervical cancer deaths in 2021–2100, with the discounted ICER being $− 339 (− 687 to − 79) per quality-adjusted life-year. Conclusions By adopting an optimal pathway from 2021 (namely, the year of the first Chinese Centennial Goals) onwards, cervical cancer could be eliminated by the late 2040s (namely, ahead of the second Chinese Centennial Goals) while saving net economic costs in China.

Introduction: Uptake of cervical cancer screening services in Chinese migrant workers is unknown and may be lower than non-migrant workers in China. Methods: We conducted a cross-sectional study among migrant and non-migrant women aged 21-65 at 7 provinces across China and administered a questionnaire investigating knowledge and attitudes regarding cervical cancer, human papillomavirus (HPV), and HPV vaccine. We used multivariable logistic regression to evaluate odds of previous cervical cancer screening in migrant workers. Results: 737 women participated in the study. Mean age was 41.9 ± 7.2 years. 50.2% of the participants were migrant workers. 27.6% of the migrant workers reported previous cervical cancer screening compared to 33.2% of local participants. 36.6% migrant workers reported awareness of HPV compared to 40.2% of local participants. In adjusted analysis migrant status was not associated with increased odds of previous cervical cancer screening (aOR = 1.11 95%CI: 0.76-1.60). High school or higher education compared to less than high school education and employer-sponsored insurance compared to uninsured were associated with increased odds of previous cervical cancer screening (aOR = 2.15 95%CI: 1.41-3.27 and aOR = 1.67 95% CI: 1.14-2.45, respectively). Having heard of HPV compared to no awareness of HPV was associated with increased odds of cervical cancer screening (aOR = 2.02 95%CI: 1.41-2.91). Awareness of HPV among migrant workers was associated with increased odds of cervical cancer screening compared to migrant and local participants without awareness (aOR = 2.82 95% CI: 1.70-4.69 and 2.97 95%CI: 1.51-5.83, respectively). Conclusions: Efforts to increase education opportunities, provide insurance, and promote HPV awareness could increase cervical cancer screening uptake in migrant women in China.

Background: Currently, knowledge of the protective effects of natural acquired immunity against human papillomavirus (HPV) is mostly based on studies using binding antibodies (IgG) as biomarkers due to the labor-consuming characteristics of neutralizing antibodies assays, and the conclusions from different studies are inconsistent. Methods: In a phase III clinical trial of the Escherichia coli-produced HPV-16/18 bivalent vaccine, participants were tested for neutralizing antibodies and IgG antibodies with pseudovirion-based neutralization assay and L1 virus-like particle-based ELISA, respectively. HPV-16 and HPV-18 infections were identified using cervical specimens periodically collected during the over 5·5 years of follow-up. Data of the 3,634 women aged 18-45 years in the control arm were used to evaluate the protective effects of the type-specific neutralizing antibodies as well as the IgG antibodies. Findings: For the persistent infection (PI) endpoints of HPV-16/18 lasting for over 6/12 months, the prevalence of type-specific neutralizing antibodies was highly protective (6 m PI: RR = 0·16, 95% CI: 0·04, 0·63; 12 m PI: RR = 0·23, 95% CI: 0·06, 0·95), while the prevalence of IgG antibodies was associated with minor and nonsignificant protection (6 m PI: RR = 0·71, 95% CI: 0·44, 1·16; 12 m PI: RR = 0·76, 95% CI: 0·43, 1·36). Women with neutralizing antibodies had a lower risk of subsequent homotypic infection, irrespective of their IgG status. In contrast, women with positive IgG while negative neutralizing antibodies showed a similar risk of subsequent infection as those with neither neutralizing nor IgG antibodies. Interpretation: The findings indicate that naturally acquired neutralizing antibodies are associated with a substantially reduced risk of subsequent homotypic infection. Funding: National Natural Science Foundation of China ; The Fujian Province Health Education Joint Research Project; Xiamen Science and Technology Major Project; Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; and Xiamen Innovax. Declaration of Interest: We declare no competing interests. Ethical Approval: Written informed consent was obtained from all participants, and the trial was conducted in accordance with Good Clinical Practice and was approved by independent ethics committees.

BACKGROUND Cervical cancer screening with cytology suffers from low sensitivity, whereas the efficiency of human papillomavirus (HPV)-based screening is limited by low specificity. The authors evaluated a novel p16INK4a immunocytology approach in cervical cancer screening compared with HPV-based and cytology-based screening. METHODS In total, 2112 women aged 49 to 69 years from Shanxi, China were screened from March to July 2019. HPV testing, liquid-based cytology (LBC), and p16INK4a immunocytology were performed on samples from all women. Any positive result triggered a referral to colposcopy with biopsy, if indicated. Screening performance for detecting cervical intraepithelial neoplasia grade 2 and 3 or worse (CIN2+/CIN3+) was evaluated using multiple algorithms. RESULTS p16INK4a had a lower positive rate (10.0%) than LBC abnormality (vs 12.1%; P = .004) and a high-risk HPV positivity (21.4%; P < .001). For the detection of CIN3+, the relative sensitivity of p16INK4a compared with HPV and LBC was 0.93 (95% CI, 0.82-1.07) and 1.12 (95% CI, 0.95-1.32), respectively. The specificity of p16INK4a was significantly higher than that for HPV and LBC, with a relative specificity of 1.13 (95% CI, 1.11-1.16) and 1.02 (95% CI, 1.01-1.04), respectively. In addition, p16INK4a alone yielded a clinical performance very similar to that of the current mainstream strategy of using HPV16/18 with reflex cytology (ASC-US+, atypical squamous cells of undetermined significance or worse). The immediate risk of CIN3+ was 14.6% if p16INK4a results were positive and 0.2% if p16INK4a results were negative. CONCLUSIONS With minimal colposcopy referrals, p16INK4a screening demonstrated promising utility for risk stratification and yielded a better balance between sensitivity and specificity compared with HPV and LBC primary screening. Moreover, with accuracy and efficiency similar to what is achieved using mainstream cotest algorithms, p16 may simplify the screening practice. More evidence will be required before clinical recommendation.

Human papillomavirus (HPV) vaccines are efficacious against HPV infections and associated lesions in women HPV-naïve at vaccination. However, vaccine efficacy (VE) against oncogenic, high-risk HPV (HR-HPV) types in women infected with any other HR-HPV type at first vaccination (baseline) remains unclear. This post-hoc analysis of a phase II/III study (NCT00779766) evaluated AS04-adjuvanted HPV-16/18 (AS04-HPV-16/18) VE against HR-HPV type infection in 871 Chinese women aged 18–25 years over a 72-month follow-up period. Study participants were DNA-negative at baseline to HR-HPV type(s) considered for VE and DNA-positive to any other HR-HPV type. Initial serostatus was not considered. Baseline DNA prevalence was 14.6% for any HR-HPV type and 10.6% excluding HPV-16/18. In the total vaccinated cohort for efficacy, VE against 6-month and 12-month HPV-16/18 persistent infections (PIs) in women DNA-negative to HPV-16/18 but DNA-positive to any other HR-HPV type at baseline was 100.0% (95% Confidence Interval [CI]: 79.8–100.0) and 100.0% (95%CI: 47.2–100.0), respectively. VE against HPV-16/18 incident infections in women DNA-positive to one vaccine type but DNA-negative to the other one at baseline was 66.8% (95%CI: −18.9–92.5). VE against HPV-31/33/45 incident infections, in women DNA-positive to HPV-16/18 and DNA-negative to the considered HPV type at baseline was 71.0% (95%CI: 27.3–89.8). No HPV-16/18 PIs were observed in vaccinated women with non-vaccine HPV A7/A9 species cervical infection at baseline. These findings indicated that women with existing HR-HPV infection at vaccination might still benefit from the AS04-HPV-16/18 vaccine. However, this potential benefit needs further demonstration in the future.

Background It is widely acknowledged that HPV prophylactic vaccine could prevent new infections and their associated lesions among women who are predominantly HPV-naive at vaccination. Yet there still remains uncertainty about whether HPV vaccination could benefit to individuals who have undergone surgery for cervical disease. Methods This post-hoc analysis intends to focus on intent-to-treat participants who underwent excision treatment at baseline and the follow-up period in a phase II/III, double-blind, randomized trial (ClinicalTrials.gov, number NCT00779766) conducted in Jiangsu province, China. We evaluate the impact of HPV vaccination on preventing women from subsequent infection and cervical lesions (LSIL+ and CIN2+) after excision treatment. Results One hundred sixty-eight (vaccine, n = 87; placebo, n = 81) performed excisional treatment in this clinical trial. We observed a significant effect of vaccination on acquiring 14 high-risk HPV (HR-HPV) infection after treatment (vaccine efficacy: 27.0%; 95% CI 4.9, 44.0%). The vaccine efficacy against new infections after treatment for 14 HR-HPV infection was estimated as 32.0% (95%CI 1.8, 52.8%), and was 41.2% (95%CI -162.7, 86.8%) for HPV16/18 infection. The accumulative clearance rates of the vaccine group and placebo group were 88.9 and 81.6% for HPV16/18 infection (P = 0.345), 63.4, 48.7% for 14 HR-HPV infection (P = 0.062), respectively. No significant difference was observed on the persistent rate of HPV16/18, 14 HR-HPV infection and occurrence rate of LSIL+ between the two groups. Conclusions No significant evidence from this study showed that HPV-16/18 AS04-adjuvanted vaccine could lead to viral faster clearance or have any effect on the rates of persistent infection among women who had excision treatment. However, the vaccine may still benefit post-treatment women with “primary prophylactic” effect. Further research is required in clarifying the effect of using the prophylactic HPV vaccine as therapeutic agents. Trial registration ClinicalTrials.gov identifier: NCT00779766. Date and status of trial registration: October 24, 2008. Completed; Has Results.

Women are anticipated to go through more than two rounds of cervical screening in their lifetime. Human papillomavirus (HPV) testing is increasingly used as the primary cervical cancer screening test. However, triage strategies for HPV-positive women were usually evaluated at baseline screening. We assessed the effect of sequential rounds of cervical screening on several algorithms for HPV triage. A total of 1,997 women ages 35–45 years were enrolled in 1999 in Shanxi, P.R. China and followed up three times at approximately 5-year intervals. Cervical intraepithelial neoplasia (CIN) grade 2 or worse (CIN2+) prevalence by prior HPV results and performance of 12 triage algorithms with cytology, genotyping, and prior HPV were examined among 229 HPV-positive women at the fourth round. CIN2+ prevalence varied from 56.5% (95% confidence interval, 36.8%–74.4%) following 15 years HPV persistence to 3.5% (1.2%–9.9%) with an incident HPV within 15 years. Triage with cytology (with threshold of atypical squamous cells of undetermined significance) yielded positive predictive value (PPV) of 21.4% (13.8%–29.0%), entailing immediate colposcopic referral, and negative predictive value (NPV) of 97.4% (94.6%–100%), permitting retesting at short intervals. Triage with genotyping (16/18/31/33/45/52/58) or prior HPV results showed comparable performance with cytology. Among 11 triage algorithms with similar NPV to cytology, triage with prior HPV results and reflex genotyping (16/18) achieved highest PPV of 28.9% (18.8%–39.1%) and lowest colposcopy referral of 33.2% (27.4%–39.5%). HPV persistence across rounds is an effective risk stratifier in HPV-positive women. Mainstream cytology and genotyping, with or without consideration of prior HPV results, remain effective for HPV triage at fourth round. Prevention Relevance: The study highlights the sustained effectiveness of mainstream HPV triage methods, such as cytology and genotyping, after sequential rounds of cervical screening. It also suggests that use of HPV persistence across rounds can improve management of HPV-positive women in cervical cancer screening.

Background Human papillomavirus (HPV) vaccine has been increasingly discussed in mainland China since its first approval in 2016. To date, nearly all studies assessing HPV vaccine perceptions and attitudes were implemented during pre-licensure period. Therefore, the nationwide post-marketing survey was conducted to update knowledge, attitudes and practice on HPV vaccine among general population in mainland China. Methods Participants aged 18–45 years living in mainland China were recruited in April 2019 by multi-stage non-randomized sampling. Sociodemographic factors, HPV and HPV vaccine related awareness, knowledge, attitudes, vaccine uptake and potential obstacles were assessed in questionnaires. Bivariate analysis and multivariate regression were used to identify disparity among subgroups with different sociodemographic characteristics. Results 4,000 women (32.1 ± 7.81y) and 1,000 men (31.8 ± 7.96y) were included in final analysis. Less than one third of participants had heard of HPV (female: 31%; male: 22%) and HPV vaccine (female: 34%; male: 23%). Knowledge score was also unfavorable on HPV (female: 3 out of 13; male: 1.8 out of 13) and HPV vaccine (female: 3 out of 6; male: 2 out of 5). Only 3% females had been vaccinated three years after HPV licensure in China, although willingness to get vaccinated among those unvaccinated were high (mean willingness score ± SD: female: 3.3 ± 0.97; male: 3.0 ± 0.98). Industry of employment and household income were the major factors related to awareness and knowledge of vaccine, whereas HPV and HPV vaccine awareness were key influential factors for willingness. The main obstacles of vaccination were safety concerns, lack of knowledge, and high price of HPV vaccines. Conclusions Findings highlight a lack of vaccine awareness, knowledge, and poor uptake in mainland China and underscore the necessity of health education campaigns. The identified priority groups, contents to be delivered and practical obstacles could furthermore provide insight into health education to reduce disparities and accelerate HPV vaccine roll-out in China.

Background How to best triage human papillomavirus (HPV) positive women remains controversial in an era of HPV primary screening of cervical cancer. Here, we assessed the long-term risk stratification for triaging HPV 16 positive women by standalone HPV 16 methylation and combined with E6 oncoprotein. Methods A total of 1742 women underwent screening with HPV DNA testing, cytology, and visual inspection with acetic acid (VIA) in 2005 and were followed for 10 years. Seventy-seven women with HPV 16 positivity determined by HPV genotyping test were examined via E6 oncoprotein detection and bisulfite pyrosequencing for quantitative methylation of L1 and LCR genes of HPV 16. Results The 10-year cumulative incidence rate (CIR) of cervical intraepithelial neoplasia grade 3 or severe (CIN3+) for HPV 16 positive women was 25.3% (95% CI 14.7–37.3%), which significantly increased in women with high methylation at six sites (CpG 5602, 6650, 7034, 7461, 31, and 37) and in women with positive E6 oncoprotein. A methylation panel based on the above six sites showed a competitive risk stratification compared to cytology (HR 11.5 vs. 8.1), with a higher 10-year CIR of CIN3+ in panel positives (57.2% vs 36.8%) and comparable low risk in panel negatives (5.7% vs 4.8%).The sensitivity and specificity for accumulative CIN3+ was 85.7% (95%CI 60.1–96.0%) and 78.4% (95%CI 62.8–88.6%) for a methylation panel and 57.1% (95%CI 32.6–78.6%) and 86.5% (95%CI 72.0–94.1%) for E6 oncoprotein. The AUC values of methylation standalone and the co-testing of methylation panel and E6 oncoprotein were around 0.80, comparable to 0.68 for cytology, 0.65 for viral load, and superior to 0.52 for VIA (p < 0.05). Conclusions Our findings indicated the promising use of HPV 16 methylation alone or combined with E6 oncoprotein for triaging HPV 16 positive women based on the long-term risk stratification ability.

Background How vaginal infections such as bacterial vaginosis, Candida spp, and Trichomonas vaginalis affect persistence of human papillomavirus (HPV) infection is not well established. Our study aimed to evaluate the association between common vaginal infections and cervical non-HPV16/18 infection, as risk factors associated with persistence of nonvaccine HPV types will become increasingly relevant in the setting of HPV vaccination. Methods We performed an analysis in 2039 AS04-HPV16/18–vaccinated women enrolled in a phase II/III trial in China, who were HPV DNA negative at month 0 and 6 and had at least 1 subsequent follow-up visit. Vaginal infections were detected in liquid-based cytology according to the diagnostic criteria of the Bethesda System. Associations between vaginal infections and incident and 6-month persistent non-HPV16/18 infections in the cervix were evaluated using generalized estimating equations, adjusting for the age at initial vaccination, as well as HPV types in the persistence analysis. Results Study visits with any vaginal infection had a statistically significant increased risk of incident non-HPV16/18 infection compared to those without vaginal infections (odds ratio [OR], 1.44 [95% confidence interval {CI}, 1.09–1.92]). However, vaginal infections were not associated with 6-month persistent non-HPV16/18 infection (OR, 1.02 [95% CI, .62–1.69]). Conclusions Our study suggests that common vaginal infections are not associated with persistence of non-HPV16/18 infection among HPV16/18-vaccinated women.

Improvement in managing HPV-positive women is urgently needed. Based on a population-based study which included 2112 women aged 49 to 69 from Shanxi, China, we aimed to evaluate the clinical performance of multiple triage strategies based on liquid-based cytology (LBC), p16INK4a , viral load and partial genotyping, as a single or combined strategy for detecting cervical intraepithelial neoplasia grade 2/3 or higher (CIN2+/CIN3+) in women who tested positive by Hybrid Capture 2 (HC2). Among 452 HC2-positive women, the test positivity of LBC (ASC-US+), p16INK4a , HPV16/18 and HPV16/18/31/33/45 were 39.6%, 38.5%, 18.0% and 40.0%, respectively. Compared to LBC (ASC-US+) triage, a single triage strategies using p16INK4a or extended genotyping (SureX HPV16/18/31/33/45) achieved comparable sensitivity (relative sensitivity: 1.08, 95% confidence interval [CI]: 0.93-1.26 and 0.96, 95% CI: 0.76-1.22) and specificity (relative specificity: 1.05, 95% CI: 0.96-1.14 and 1.02, 95% CI: 0.92-1.14) for CIN3+. Viral load triage using a ≥50 RLU/CO cut-point also yielded similar results with LBC (ASC-US+). Among combined triage strategies, HPV16/18 genotyping with reflex p16INK4a showed higher sensitivity and slightly lower specificity than LBC (ASC-US+) for CIN3+ detection, however, the differences were not statistically significant. Of note, after a negative result by p16INK4a or LBC among HPV16/18 negative women, the posttest probability of CIN3+ was lower than 1%. Our study suggested that p16INK4a , extended genotyping and increased viral load cut-point could be promising alternatives to cytology triage. Combined triage algorithms of HPV16/18 with reflex p16INK4a or cytology, if negative, are associated with the substantial low posttest risk sufficient to release women to next screening round.

BACKGROUND Biomarkers highly predictive of cervical cancer are urgently needed for triaging human papillomavirus (HPV)-positive women. METHODS A total of 1997 women aged 35-45 years in Shanxi, China, were recruited in 1999, and follow-up visits were conducted in 2005, 2010, and 2014. HPV load was measured by the Hybrid Capture 2 assay. Findings were determined by relative light units/cutoff (RLU/CO) and categorized into 4 groups: negative (

The management of HPV-positive women becomes particularly crucial in cervical cancer screening. Here we assessed whether detection of E6 or E7 oncoproteins targeting eight most prevalent HPV types could serve as a promising triage option. Women (N = 1,416) aged 50-60 from Shanxi, China underwent screening with HPV testing and liquid-based cytology (LBC), with any positive results referring to colposcopy and biopsy if necessary. Women with HPV-positive results received further tests using DNA-based genotyping, E6 or E7 oncoprotein detection targeting HPV16/18 (for short: E6 (16/18) Test) or HPV16/18/31/33/35/45/52/58 (for short: E6/E7 (8 types) Test), respectively. Among HPV-positive women, E6/E7 (8 types) oncoproteins had lower positivity (17.37%) compared to DNA-based genotyping for same eight types (58.30%) and LBC with ASC-US threshold (50.97%); HPV16 was the genotype showing the highest frequency (8.49%) for oncoprotein detection followed by HPV52 (3.47%), 58 (2.32%), 33 (1.54%), 18 (1.16%), 45 (0.77%), 35 (0.39%) and 31 (0%). For detection of cervical intraepithelial neoplasia Grade 3 or higher (CIN3+), E6/E7 (8 types) Test had similar sensitivity (100.00%) and superior specificity (85.94%) as well as positive predictive value (PPV, 22.22%) compared to both LBC and DNA-based genotyping (8 types); For detection of CIN2+, E6/E7 (8 types) Test was less sensitive (67.74%) but still more specific (89.47%) and risk predictive with PPV of 46.67%. Notably, E6/E7 (8 types) Test remarkably decreased the number of colposcopies needed to detect one CIN2+ and CIN3+ (2.14 and 4.50). E6/E7 oncoprotein detection showed a good "trade-off" between sensitivity and specificity with more efficient colposcopy referrals, which is of great importance to maximize the benefits of HPV-based screening program, especially applicable for the areas with high HPV prevalence and low-resources.

ASCCP cervical cancer screening guidelines recommend triaging high-risk human papillomavirus (hrHPV) positive women with cytology and genotyping, but cytology is often unavailable in resource-limited areas. We compared the long-term risk of cervical cancer and precancers among type-specific hrHPV-positive women triaged by viral load to cytology and visual inspection with acetic acid (VIA).A cohort of 1742 Chinese women was screened with cytology, VIA, and Hybrid Capture 2 (HC2) test and followed for ten years. All HC2-positive samples were genotyped. Viral load was measured by HC2 relative light units/cutoff (RLU/CO). Ten-year cumulative incidence rate (CIR) of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) for type-specific hrHPV viral load was estimated using Kaplan-Meier methods.Baseline hrHPV viral load stratified by specific genotypes was positively correlated with prevalent cytological lesions. Ten-year CIR of CIN2+ was associated with cytological lesions and viral load. Among HPV 16/18-positive women, ten-year CIR of CIN2+ was high, even with normal cytology (15.3%), normal VIA (32.4%), viral load with RLU/CO10 (23.6%) or RLU/CO100 (33.8%). Among non-16/18 hrHPV positive women, ten-year CIR of CIN2+ was significantly stratified by cytology grade of atypical squamous cell of undetermined significance or higher (2.0% VS. 34.6%), viral load cutoffs at 10 RLU/CO (5.1% VS. 27.2%), at 100 RLU/CO (11.0% VS. 35.5%), but not by VIA (19.1% VS. 19.0%).Our findings support the guidelines in referring all HPV16/18 positive women to colposcopy and suggest triaging non-16/18 hrHPV positive women using viral loads in resource-limited areas where cytology screening was inaccessible.

Summary Background Although recent studies have suggested that naturally acquired Human papillomavirus (HPV) antibodies are partly protective against subsequent homotypic infection, the extent of protection remains indecisive. Here, we evaluate the protective effect of neutralizing and IgG antibodies simultaneously. Methods In a cohort of 3634 women aged 18-45 years from the control arm of a phase III trial of the HPV-16/18 bivalent vaccine, participants were tested for neutralizing antibodies by pseudovirion-based neutralization assay (PBNA) and IgG antibodies by enzyme-linked immunosorbent assay (ELISA) at baseline. HPV-16/18 incident and persistent infections were identified using cervical specimens periodically collected during the 5·5 years of follow-up. The protective effects of HPV-16/18 neutralizing and IgG antibodies against homotypic infection were assessed using a Cox proportional hazard model. Findings For the persistent infection (PI) endpoints of HPV-16/18 lasting for over 6/12 months, a prevalence of type-specific neutralizing antibodies was highly protective (6-month PI: hazard ratio (HR) = 0·16, 95% confidence interval (CI): 0·04, 0·65; 12-month PI: HR = 0·23, 95% CI: 0·06, 0·94), whereas a prevalence of IgG antibodies was associated with minor and non-significant protection (6-month PI: HR = 0·66, 95% CI: 0·40, 1·09; 12-month PI: HR = 0·66, 95% CI: 0·36, 1·20). After increasing the cut-off value to the median IgG level, the risk of 6-month PI was significantly lower in seropositive vs seronegative women (HR = 0·38, 95% CI: 0·18, 0·83). Interpretation Naturally acquired antibodies are associated with a substantially reduced risk of subsequent homotypic infection. Funding NSFC; The Fujian Province Health Education Joint Research Project; Xiamen Science and Technology Major Project; CIFMS; and Xiamen Innovax.

E6 oncoprotein is a necessary agent of HPV driven oncogenic transformation. This study is aimed at evaluating the risk stratification potency of HPV 16/18 E6 oncoprotein (E6) as a triage method for HPV positivity. Moreover, it also acts as a predictor of cervical intraepithelial neoplasia grade 3 or worse (CIN3+). The screening cohort of 1,997 women was followed for a 15 year period in approximate five-year intervals. Participants were concurrently screened by HPV DNA testing (HC2), liquid based cytology (LBC), visual inspection with acetic acid (VIA), and were referred to colposcopy and biopsy if any tests reflected positive. E6 was performed on cervical samples collected from this cohort in 2005 and 2014. The ability of E6 to predict CIN3+ risk after the five and ten year interval was evaluated. Among HPV positive women in 2005, E6 indicated the lowest positive rate (9.9%) compared to LBC (48.4%) and VIA (28.0%), however, a higher prevalence rate (10.3%) and ten year cumulative incidence rate (53.0%) of CIN3+ were detected among women who were E6 positive. Meanwhile, only approximately 4.2% and 2.9% of women with abnormal LBC and positive VIA were diagnosed as prevalent CIN3+ in 2005, 23.0% and 16.5% developed to CIN3+ after year ten, respectively. Strong associations were found between precedent and subsequent HPV persistence and E6 oncoprotein expression (ORadjusted=40.0 and 21.2 respectively). E6 oncoprotein can serve as a low-cost, highly specific, strongly indicative point-of-care method in the triage and treatment of HPV positive women. This article is protected by copyright. All rights reserved.

Objective CareHPV is a human papillomavirus (HPV) DNA test for low-resource settings (LRS). This study assesses optimum triage strategies for careHPV-positive women in LRS. Methods A total of 2,530 Chinese women were concurrently screened for cervical cancer with visual inspection with acetic acid (VIA), liquid-based cytology and HPV testing by physician- and self-collected careHPV, and physician-collected Hybrid Capture 2 (HC2). Screen-positive women were referred to colposcopy with biopsy and endocervical curettage as necessary. HPV-positivity was defined as ≥1.0 relative light units/cutoff (RLU/CO) for both careHPV and HC2. Primary physician-HC2, physician-careHPV and self-careHPV and in sequential screening with cytology, VIA, or increased HPV test-positivity performance, stratified by age, were assessed for cervical intraepithelial neoplasia (CIN) grade 2/3 or worse (CIN2/3+) detection. Results The sensitivities and specificities of primary HPV testing for CIN2+ were: 83.8%, 88.1% for physician-careHPV; 72.1%, 88.2% for self-careHPV; and 97.1%, 86.0% for HC2. Physician-careHPV test-positive women with VIA triage had a sensitivity of 30.9% for CIN2+ versus 80.9% with cytology triage. Self-careHPV test-positive women with VIA triage was 26.5% versus 66.2% with cytology triage. The sensitivity of HC2 test-positive women with VIA triage was 38.2% versus 92.6% with cytology triage. The sensitivity of physician-careHPV testing for CIN2+ decreased from 83.8% at ≥1.0 RLU/CO to 72.1% at ≥10.00 RLU/CO, while the sensitivity of self-careHPV testing decreased from 72.1% at ≥1.0 RLU/CO to 32.4% at ≥10.00 RLU/CO; similar trends were seen with age-stratification. Conclusions VIA and cytology triage improved specificity for CIN2/3 than no triage. Sensitivity with VIA triage was unsuitable for a mass-screening program. VIA provider training might improve this strategy. Cytology triage could be feasible where a high-quality cytology program exists. Triage of HPV test-positive women by increased test positivity cutoff adds another LRS triage option.

Summary Background The incidence of cervical cancer in China is increasing rapidly. We aimed to forecast the age-standardised incidence of cervical cancer in China up to 2100, and to determine the optimal strategy to eliminate cervical cancer under different budget scenarios. Methods In our modelling study, we developed an adapted and calibrated hybrid model to estimate the incidence of cervical cancer in urban and rural China until 2100. All 1·15 billion Chinese women living or projected to live during 2015–2100, under the projected trends in ageing, urbanisation, and sexual activity were considered. We assessed several scenarios of budget constraints (a current budget [2012–18], twice the current budget, and no budget constraints), implementation of human papillomavirus vaccination (with different target populations and coverage), and cervical cancer screening characteristics (with different target ages, screening intervals, and coverage). We used a budget optimisation process to select the best available combinations of vaccination and screening. The primary outcomes were the annual incidence of cervical cancer in 2015–2100, and the year of elimination (the first year in which the incidence was expected to be lower than four new cases per 100 000 women). Findings Under the current strategy, by 2100, the age-standardised incidence of cervical cancer is projected to increase to three times the incidence in 2015. However, if China adopts an optimal strategy under the current budget from 2020 onwards (namely, introducing vaccination of 95% coverage for girls aged 12 years, and expanding coverage of once in a lifetime screening for women aged 45 years of 90% in urban areas and 33% in rural areas), the annual age-standardised incidence of cervical cancer is predicted to decrease to fewer than four new cases per 100 000 women (ie, elimination) by 2072 (95% CI 2070–74) in urban China and 2074 (2072–76) in rural China. If the current budget were doubled from 2020 onwards, elimination would be achieved by 2063 (2059–66) in urban China and 2069 (2066–71) in rural China. The earliest possible year of cervical cancer elimination would be 2057 (2053–60) in urban China and 2060 (2057–63) in rural China, if vaccination coverage for girls aged 12 years and coverage of screening at 5-year intervals for women aged 35–64 years was maximised, with no budgetary restrictions. Interpretation Cervical cancer incidence in China will continue to increase under current cervical cancer prevention strategies. However, under our budget optimisation strategy from 2020 onwards, cervical cancer could be eliminated as a public health problem by the early 2070s. Elimination could be achieved by the late 2050s by increasing the budget towards vaccination against human papillomavirus and cervical cancer screening. Funding National Natural Science Foundation of China and Chinese Academy of Medical Science Initiative for Innovative Medicine.

The main objective of this work is to determine the performance of urine for human papillomavirus (HPV) detection in cervical cancer screening in screening population. Paired urine and cervical samples were collected from 2038 women (careHPV group: 1002, cobas4800 group: 1036) in 2015. Urine was tested by a new urine-based HPV test and cervical samples by careHPV or cobas4800 HPV test. Women were triaged based on cervical results and then referred to colposcopy with biopsy as clinically indicated. In 2017, women were followed up and screened with cotesting strategy, women with any positive would be referred and biopsied if necessary. In careHPV group, the HPV prevalence of urine was 14.1%, and 16.4% for cervical samples. In cobas4800 group, it was 19.1% and 20.4%, correspondingly. The concordance of urine samples compared with cervical samples was moderate (careHPV group: 86.6%; κ = 0.48; cobas4800 group: 83%; κ = 0.46). The baseline sensitivity and specificity for urine against CIN2+ detection were 85.7%, 86.8% in careHPV group, and 69.2%, 82.3% in cobas4800 group, respectively. Cervical samples were 100% sensitive for both tests (careHPV and cobas4800) and 85.2% specific in careHPV group and 81.9% specific in cobas4800 group, respectively. The corresponding cumulative sensitivity and specificity were 68.8% and 87.1%, 58.8% and 81.9%, 87.5% and 85.5%, and 94.1% and 81.4%. Urine demonstrated certain potential in cervical cancer screening and could be an alternative if no better screening strategies available.

Since licensure of human papillomavirus (HPV) vaccine in mainland China, little research has been conducted about healthcare providers' (HCPs) understanding and recommendation of HPV vaccine. A multi-stage convenience sample of Chinese HCPs (N = 5270) were surveyed, involving obstetrician-gynecologists, HCPs from Division of Expanded Program on Immunization (DEPI), Community Health Center (CHC) and other non-HPV closely related professions. Binary logistic regression was conducted to explore factors associated with knowledge and recommendation behaviors. Overall, HCPs showed basic HPV/HPV vaccine knowledge with median (interquartile range) score at 9.5 (7.5–11.6) out of 16 and relatively high recommendation behavior (74.8%). Identified knowledge gaps among HCPs included risk factors of HPV infection, best time to vaccinate, prophylactic functions of HPV vaccine and especially classification of low-risk and high-risk types. Profession-specific analysis in individual knowledge item showed HCPs from CHC were suboptimal on HPV while obstetrician-gynecologists were less competent on HPV vaccine knowledge. Obstetrician-gynecologists also recommended vaccination less frequently than HCPs from DEPI and CHC. Besides being key predictors of recommendation practice (2.74, 95% CI: 2.34–3.21), knowledge shared independent determinants with recommendation behavior on age and ethnicity and additionally associated with education and title by itself. Findings highlight overall and profession-specific gaps on HPV and HPV vaccine knowledge and recommendation practice. Future education and training efforts should be profession-niche-targeting and focus much on HCPs with lower title or education background and from minorities.

We previously reported the results of a phase II/III, double‐blind, randomized controlled study in Chinese women (NCT00779766) showing a 94.2% (95% confidence interval: 62.7–99.9) HPV‐16/18 AS04‐adjuvanted vaccine efficacy (VE) against cervical intraepithelial neoplasia grade 1 or higher (CIN1+) and/or 6‐month (M) persistent infection (PI) with a mean follow‐up of

As China's population ages, the importance of determining prevalence of cervical disease and accurate cervical cancer screening strategies for postmenopausal women is increasing.17 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 4 quadrants biopsy as reference standard. Premenopausal and postmenopausal women had equal HPV infection and cervical neoplasia rates (p-value >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 and 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 maintained performance between pre- and postmenopausal women and is the most accurate primary modality for screening postmenopausal populations in low resource areas of China. This article is protected by copyright. All rights reserved.

Three different cervical screening methods [cytology, human papillomavirus(HPV) testing and visual inspection with acetic acid(VIA)] are being considered in China for the national cervical screening program. Comparing risks of CIN3 and cervical cancer (CIN3+) for different results can inform test choice and management guidelines. We evaluated the immediate risk of CIN3+ for different screening results generated from individual and combined tests. We compared tests using a novel statistic designed for this purpose called Mean Risk Stratification (MRS), in a pooled analysis of 17 cross sectional population-based studies of 30,371 Chinese women screened with all 3 methods and diagnosed by colposcopically-directed biopsies. The 3 tests combined powerfully distinguished CIN3+ risk; triple-negative screening conferred a risk of 0.01%, while HPV-positive HSIL+ that was VIA-positive yielded a risk of 57.8%. Among the three screening tests, HPV status most strongly stratified CIN3+ risk. Among HPV-positive women, cytology was the more useful second test. In HPV-negative women, the immediate risks of CIN3+ ranged from 0.01% (negative cytology), 0.00% (ASC-US), 1.1% (LSIL), to 6.6 (HSIL+). In HPV-positive women, the CIN3+ risks were 0.9% (negative cytology), 3.6% (ASC-US), 6.3% (LSIL) and 38.5% (HSIL+). VIA results did not meaningful stratify CIN3+ risk among HPV-negative women with negative or ASC-US cytology; however, positive VIA substantially elevated CIN3+ risk for all other, more positive combinations of HPV and cytology compared with a negative VIA. Because all 3 screening tests had independent value in defining risk of CIN3+, different combinations can be optimized as pragmatic strategies in different resource settings.

Objectives: Human papillomavirus is the necessary cause of cervical cancer, in particular the human papillomavirus-16/18 strains, which have been detected in ~70% of all cervical cancer cases worldwide. This study aims to assess whether other cofactors, which might be specific for the Chinese population, are involved in the development of cervical cancer. These findings may support the future direction of cervical cancer prevention. Study Design: Systematic literature review. Methods: The following databases were searched: MEDLINE, MEDLINE-IN-PROCESS, EMBASE, China National Knowledge Infrastructure, Wanfang Data and Chongqing VIP Information. The target population were adolescents or adults from mainland China. All observational studies irrespective of intervention or comparator reporting risk factors for cervical cancer were included. The Newcastle-Ottawa Scale was used to assess study quality. The impact of each outcome was reported in numerical terms. Results: A total of 2,676 articles were screened. A total of 21 articles met the inclusion criteria. All studies were case-controlled designs mostly conducted in hospitals of South-Eastern China. A total of 18 studies reported lifestyle behaviours as significant influencing factors in the development of cervical cancer. Sexual behaviour, gestational factors, screening history, disease history and socio-demographics status were reported as significant risk factors for cervical cancer development. Conclusion: This review provides an up-to-date insight of current cervical cancer risk factors in China. Due to the heterogeneity of the results, further evaluation is recommended to determine the association of these risk factors to the overall risk of cervical cancer.

Objective Self-collected HPV testing could substantially reduce disparities in cervical cancer screening, with slightly lower sensitivity compared to physician-collected specimens cross-sectionally. We aimed to evaluate the comprehensive long-term performance of self-collected HPV testing prospectively. Methods In 1999, 1997 women were screened by HPV testing on self-collected and physician-collected samples, cytology and visual inspection with acetic acid (VIA) and followed up in 2005, 2010 and 2014, respectively. HPV testing was performed with Hybrid Capture II. Prospective performance, baseline clinical efficiency, and 15-year cumulative risk of cervical intraepithelial neoplasia grade 2 or higher (CIN2+) were analyzed. Results Self-collected HPV testing prospectively detected 83.3% (95% CI:74.9%,89.3%), 70.3% (95% CI:62.5%,77.2%) and 63.3% (95% CI:55.7%, 70.2%) of cumulative CIN2+ at 6-year, 11-year and 15-year follow-up, respectively. Relative cumulative sensitivity of physician-collected HPV testing versus self-collected HPV testing was stable over 15 years at about 1.16. Cumulative sensitivity of self-collected HPV testing was comparable to cytology and significantly higher than VIA. Among women positive by self-collected HPV testing at baseline, 26.2% (95% CI:21.5%, 30.9%) developed CIN2+ during 6-year follow-up and no difference was observed with physician-collected HPV testing even 15 years after baseline. Negative self-collected HPV results provided greater protection against CIN2+ than VIA and ascertained CIN2+ cumulative incident rates as low as 1.1% at the 6-year follow-up. Conclusions Self-collected HPV testing demonstrates lower sensitivity than physician-collected HPV testing but performs comparably to cytology prospectively and provides satisfactory assurance against CIN2+, indicating an alternative role in cervical cancer primary screening with five-year interval as an option especially in low-resource settings.

Treatment of cervical premalignant lesions (cervical intraepithelial neoplasia; CIN) of different grades is very effective, simple, and safe. The entire transformation zone of the cervix needs to be treated either by an ablative technique (cryotherapy or thermal ablation) or an excisional technique (large loop excision of transformation zone or cold knife conization); the choice of treatment depends on the size and location of the lesion and the type of the transformation zone. The cure rate after ablative treatment of high-grade CIN may be little lower than that after excisional treatment. The simplicity of the technique, low complication rate, and lesser cost make ablative technique the treatment of choice in the low resourced settings for the eligible lesions. In situations where organizing colposcopy and histopathology services is challenging, simple algorithms like screening with visual inspection with acetic acid test and immediate ablative treatment of the visual inspection with acetic acid-positive women has been recommended by the World Health Organization. Such a strategy is effective in preventing subsequent development of high-grade CIN and also ensures high compliance of the screen positive women to treatment.

Risk stratification of human papillomavirus (HPV)-positive women is needed to avoid excessive colposcopy and overtreatment in cervical cancer screening. We aimed to evaluate the predictive value of type-specific HPV in detecting cervical cancer and precancers in a Chinese population–based cohort and provide evidence of HPV genotyping to triage HPV-positive women. We typed all Hybrid Capture 2–positive cytologic samples of 1,742 women in Shanxi Province Cervical Cancer Screening Study cohort. Cumulative risks of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) among HPV-positive women and cumulative detection rates of CIN2+ among general women by type-specific HPV were estimated during the course of 10-year follow-up. HPV 16 and HPV 52 were most prevalent types among the screening population. Ten-year cumulative risk of CIN2+ was 47.5% [95% confidence interval (CI), 31.6–62.3] for HPV 16–positive women and 46.3% (95% CI, 15.3–75.4) for HPV 31–positive women. Ten-year cumulative risks of CIN2+ among HPV 58, 39, 33, 18, and 52 positive women ranged from 34.3% to 12.0% in a decreasing order. CIN2+ risks were found to be positively associated with infection times of the same genotypes of HPV 16, 31, 33, and 58 (all Ptrend < 0.001). Cumulative detection rates of CIN2+ within 10 years were predominantly contributed by HPV 16, 31, and 58. Our results support the risk-based management of HPV-positive women using HPV genotyping and also indicate the significance of including HPV 31 and 58 apart from commonly acknowledged HPV 16 and HPV 18 in achieving better risk stratification. Cancer Prev Res; 10(12); 745–51. ©2017 AACR.

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.

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.