Evaluation of triage strategies for high-risk human papillomavirus-positive women in cervical cancer screening: A multicenter randomized controlled trial in different resource settings in China.

Objective: We aimed to evaluate the effectiveness of different triage strategies for high-risk human papillomavirus (hrHPV)-positive women in primary healthcare settings in China. Methods: This study was undertaken in 11 rural and 9 urban sites. Women aged 35-64 years old were enrolled. HrHPV-positive women were randomly allocated to liquid-based cytology (LBC), visual inspection with acetic acid and Lugol's iodine (VIA/VILI) (rural only) triage, or directly referred to colposcopy (direct COLP). At 24 months, hrHPV testing, LBC and VIA/VILI were conducted for combined screening. Results: In rural sites, 1,949 hrHPV-positive women were analyzed. A total of 852, 218 and 480 women were randomly assigned to direct COLP, LBC and VIA/VILI. At baseline, colposcopy referral rates of LBC or VIA/VILI triage could be reduced by 70%-80%. LBC (n=3 and n=7) or VIA/VILI (n=8 and n=26) could significantly decrease the number of colposcopies needed to detect one cervical intraepithelial neoplasia (CIN) 2 or worse and CIN3+ compared with direct COLP (n=14 and n=23). For the 24-month cumulative detection rate of CIN2+, VIA/VILI triage was 0.50-fold compared with LBC triage and 0.46-fold with the direct COLP. When stratified by age, baseline LBC triage+ performed best (P<0.001), peaking among women aged 35-44 years (Ptrend=0.002). In urban sites, 1,728 women were hrHPV genotyping test positive. A total of 408, 571 and 568 women were randomly assigned to direct COLP for HPV16/18+, direct COLP for other hrHPV subtypes+, and LBC triage for other hrHPV subtypes+. LBC (n=12 and n=31) significantly decreased the number of colposcopies needed to detect one CIN2+ and CIN3+ compared with direct COLP (n=14 and n=44). HPV16/18+ increased the 24-month cumulative detection rate of CIN2+ (17.89%, P<0.001). Conclusions: LBC triage for hrHPV-positive women in rural settings and direct COLP for HPV16/18+ women and LBC triage for other hrHPV subtype+ women in urban settings might be feasible strategies.

Clinicopathological and surgical comparisons of differentiated thyroid cancer between China and the USA: A multicentered hospital-based study.

Background: Thyroid cancer (TC), was the fastest-rising tumor of all malignancies in the world and China, predominantly differentiated thyroid cancer (DTC). However, evidence on TC stage distribution and influencing factors of late-stage were limited in China. Methods: We carried out a retrospective study and enrolled TC patients who were first diagnosed and hospitalized in 8 hospitals in China in 2017. Logistic regression was used to evaluate associations between influencing factors and DTC stage. We extracted eligible primary DTC records newly diagnosed in 2017 from the USA's Surveillance, Epidemiology, and End Results (SEER) database. We compared clinicopathological features and surgical treatment between our DTC records and those from the SEER database. Results: A total of 1970 eligible patients were included, with 1861 DTC patients with known stage. Among patients ≥45 years old, males (OR = 1.76, 95%CI 1.17-2.65) and those with new rural cooperative medical scheme insurance (NCMS) (OR = 1.99, 95%CI 1.38-2.88) had higher risks of late-stage DTC (stage III-IV). Compared with SEER database, over-diagnosis is more common in China [more DTC patients with onset age< 45 years old (50.3 vs. 40.7%, P < 0.001), with early-stage (81.2 vs. 76.0%, P < 0.001), and with tumors<2cm (74.9 vs. 63.7%, P < 0.001)]. Compared with the USA, TC treatment is more conservative in China. The proportion of lobectomy in our database was significantly higher than that in the SEER database (41.3 vs. 17.0%, P < 0.001). Conclusions: Unique risk factors are found to be associated with late-stage DTC in China. The differences in the aspect of clinicopathological features and surgical approaches between China and the USA indicate that potential over-diagnosis and over-surgery exist, and disparities on surgery extent may need further consideration. The findings provided references for other countries with similar patterns.

Factors associated with persistence and clearance of HPV16/18 among rural Chinese women: a cohort study in Wufeng, Hubei province.

Human papillomavirus (HPV) persistence is the most critical cause of cervical cancer. This study focuses on exploring the prevalence and risk factors related to persistent HPV infection among rural Chinese women. Participants were recruited through a multi-stage stratified cluster sample. A total of 847 women were initially selected in 2015, and 159 were detected HPV-DNA positive at baseline. A two-year follow-up was conducted for those who were HPV-DNA positive at baseline. HPV infection was evaluated at both baseline and follow-up. Depending on the results of two HPV tests, women were divided into two categories: (1) persistence; (2) clearance. Student's t, chi-square and logistic regression were employed to find the risk factors for HPV persistence and the relationship between HPV persistence and cervical intraepithelial neoplasia (CIN). Among 129 participants with HPV16/18 infection at baseline, 60 (46.51 percent) were reported to have persistent HPV16/18 infection. Oral contraceptive use and menopause were the significant factors related to persistent HPV16/18 infection. The persistence of HPV infection was significantly related to CIN. Our results indicate that better HPV prevention strategies for rural Chinese women should be developed.

Effectiveness of High-risk Human Papillomavirus Testing for Cervical Cancer Screening in China: A Multicenter, Open-label, Randomized Clinical Trial.

IMPORTANCE: Evidence is needed regarding the introduction of high-risk human papillomavirus (hrHPV) testing into China's national cervical cancer screening program. OBJECTIVE: To evaluate hrHPV testing as a new screening modality for the national program. DESIGN, SETTING, AND PARTICIPANTS: This population-based, multicenter, open-label, randomized clinical trial took place across 20 primary health care centers in urban and rural areas across China. At least 3000 women aged 35 to 64 years per site were invited to participate, for a total of 60 732 women evaluated. INTERVENTIONS: At baseline, women were randomly assigned to cytology, hrHPV testing, or visual inspection with acetic acid and Lugol iodine (VIA/VILI) (rural only). Women who tested positive for hrHPV were randomized into cytology-triage, VIA/VILI-triage (rural only), or direct colposcopy arms. Regarding primary or triaging tests, women with cytological abnormalities or who tested positive with VIA/VILI were referred to colposcopy. After 24 months, combined screening of cytology, hrHPV testing, and VIA/VILI was performed, and all women with positive results were referred to colposcopy. MAIN OUTCOMES AND MEASURES: The primary outcomes were cervical intraepithelial neoplasia grade 2 or worse (CIN2+) and CIN3+ yields. The secondary outcome was colposcopy referral rate. RESULTS: A total of 60 732 women were included in this study, with median (interquartile range) age of 47 (41-52) years. Among urban women, 8955 were randomized to cytology and 18 176 to hrHPV genotyping; among rural women, 11 136 were randomized to VIA/VILI, 7080 to cytology, and 15 385 to hrHPV testing. Participants who tested positive for hrHPV with direct colposcopy had higher risk ratios for disease yields at baseline (urban hrHPV vs cytology, CIN2+ 2.2 [95% CI, 1.6-3.2] and CIN3+ 2.0 [95% CI, 1.2-3.3]; rural hrHPV vs cytology, 2.6 [95% CI, 1.9-4.0] and 2.7 [95% CI, 2.0-3.6]; rural hrHPV vs VIA/VILI, 2.0 [95% CI, 1.6-2.3] and 2.3 [95% CI, 1.8-3.1]). At 24 months, baseline-negative women in the hrHPV arm had significantly lower risk ratios than those with cytology, or VIA/VILI for CIN2+ (0.3 [95% CI, 0.2-0.5], 0.3 [95% CI, 0.2-0.6]) and CIN3+ (0.3 [95% CI, 0.1-0.6], 0.4 [95% CI, 0.2-0.8]) in rural sites. The colposcopy referral rate for hrHPV-positive rural women was reduced to 2.8% by cytology triage, with significantly higher CIN2+ yields than cytology (2.1 [95% CI, 1.3-2.6]) or VIA/VILI arm (1.6 [95% CI, 1.03-2.1]). Genotyping for hrHPV with cytology triage significantly reduced the colposcopy referral rate compared with cytology (0.8 [95% CI, 0.7-0.9]) for urban women. CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, testing for hrHPV was an effective primary screening method in primary health care centers. Incorporating hrHPV testing (polymerase chain reaction-based for urban areas, hybrid capture-based for rural areas) into China's national screening program is reasonable. TRIAL REGISTRATION: Chinese Clinical Trial Registry Identifier: ChiCTR1900022530.

Protection motivation theory in predicting cervical cancer screening participation: A longitudinal study in rural Chinese women.

OBJECTIVE: To examine factors longitudinally associated with cervical cancer screening uptake among rural Chinese women, guided by protection motivation theory (PMT). METHODS: A large sample of women (n = 2408, aged 35-65 years old) was randomly selected from a rural county in China in 2015 and followed up for 2 years. Data for demographic factors, knowledge of cervical cancer screening, screening outcome, and six PMT constructs measured at the baseline in 2015 were used to predict cervical cancer screening participation at the follow-up in 2017 using structural equation model method. RESULTS: Among the 2408 women at the baseline, 1879 (78.03%) participated in the screening services at the follow-up. In addition to significant direct effect of age, social status and baseline screening outcome, and three (perceived severity, fear arousal and response efficacy) of the six PMT subconstructs, four variables (age, social status, knowledge of cervical cancer screening, and baseline screening outcome) at the baseline were indirectly associated with screening participation, mediated by the three significant PMT subconstructs. CONCLUSIONS: Findings of this study indicate that the rate of participating in cervical cancer screening for rural women needs to be further improved. In addition to the commonly reported influential factors, PMT subconstructs play important roles in encouraging rural women in China to participate in cervical cancer screening. These longitudinal findings provided data much needed for future research to develop evidence-based intervention programs to enhance cervical cancer screening among rural women in China.

Human papillomavirus type 18/16 infection and prevalence among middle-aged and older Chinese rural women: a cross-sectional survey in Wufeng, Hubei Province.

This study aimed to measure the prevalence and potential factors related to HPV 16/18 infection among middle-aged and older Chinese rural women. The study was conducted among women aged 35-65 years in rural villages within Wufeng in Hubei Province. Data were collected using a pretested questionnaire between July and August 2015. Cervical specimens were collected for HPV DNA detection and typing by using careHPV. Pearson's Chi-square and logistic regression analyses were used to examine associations with HPV positivity. Among 1001 participants, the prevalence of HPV 18/16 positive genotyping was 15.88% (n = 159). Husbands' extramarital sex (adjusted odds ratio [OR] = 15.85, 95% confidence interval [CI] 5.76-43.59), cervicitis (adjusted OR = 9.27, 95% CI 5.06-16.99), condom usage (adjusted OR = 0.16, 95% CI 0.05-0.53), higher average number of live births (adjusted OR = 1.98, 95% CI 1.32-2.96 for two live births; adjusted OR = 3.29, 95% CI 1.39-7.81 for three or more live births) were associated with HPV infection. The prevalence of HPV infection among participating women from rural areas was higher than that in several other areas in China. Our findings can aid efforts to prevent HPV infection to lower the risk of cervical cancer.

Protection motivation theory in predicting intention to receive cervical cancer screening in rural Chinese women.

OBJECTIVE: Despite the significance of cervical cancer screening, motivating more women to participate remains a challenge in resource-limited settings. In this study, we tested the protection motivation theory (PMT) in predicting screening intentions. METHODS: Participants were women from Wufeng, a typical rural county in China. Participants (n = 3000) with no cervical cancer history were recruited from 10 randomly selected villages. As mediating variables, 6 PMT constructs (Perceived Risk, Fear Arousal, Perceived Severity, Response Efficacy, Response Cost, and Self-Efficacy) were measured using the standardized questionnaire. Structural equation modeling (SEM) method was employed to test PMT-based prediction models. RESULTS: Of the total sample, 57.77% believed that regular screening may reduce cervical cancer risk, and 45.26% agreed that women should be screened regularly. Our data fit the PMT model well (GFI = 0.95, AGFI = 0.93, CFI = 0.90, RMSEA = 0.06, SRMR = 0.04, Chi-square/df = 2.47). Knowledge of screening was directly and positively associated with screening intention. Age, annual income, and awareness of and prior experience with screening were significantly associated with screening intention by enhancing cervical cancer risk perception and by reducing response cost (P<0.05 for both). CONCLUSION: PMT can be used as guidance to investigate cervical cancer screening intentions among rural women in China with focus on cancer knowledge, some demographic factors, and awareness of and previous experience with screening. These findings, if verified with longitudinal data, can be used for intervention program development.