Cost-effectiveness of the screen-and-treat strategies using HPV test linked to thermal ablation for cervical cancer prevention in China: a modeling study.

BACKGROUND: Self-sampling HPV test and thermal ablation are effective tools to increase screening coverage and treatment compliance for accelerating cervical cancer elimination. We assessed the cost-effectiveness of their combined strategies to inform accessible, affordable, and acceptable cervical cancer prevention strategies. METHODS: We developed a hybrid model to evaluate costs, health outcomes, and incremental cost-effectiveness ratios (ICER) of six screen-and-treat strategies combining HPV testing (self-sampling or physician-sampling), triage modalities (HPV genotyping, colposcopy or none) and thermal ablation, from a societal perspective. A designated initial cohort of 100,000 females born in 2015 was considered. Strategies with an ICER less than the Chinese gross domestic product (GDP) per capita ($10,350) were considered highly cost-effective. RESULTS: Compared with current strategies in China (physician-HPV with genotype or cytology triage), all screen-and-treat strategies are cost-effective and self-HPV without triage is optimal with the most incremental quality-adjusted life-years (QALYs) gained (220 to 440) in rural and urban China. Each screen-and-treat strategy based on self-collected samples is cost-saving compared with current strategies (-$818,430 to -$3540) whereas more costs are incurred using physician-collected samples compared with current physician-HPV with genotype triage (+$20,840 to +$182,840). For screen-and-treat strategies without triage, more costs (+$9404 to +$380,217) would be invested in the screening and treatment of precancerous lesions rather than the cancer treatment compared with the current screening strategies. Notably, however, more than 81.6% of HPV-positive women would be overtreated. If triaged with HPV 7 types or HPV16/18 genotypes, 79.1% or 67.2% (respectively) of HPV-positive women would be overtreated with fewer cancer cases avoided (19 cases or 69 cases). CONCLUSIONS: Screen-and-treat strategy using self-sampling HPV test linked to thermal ablation could be the most cost-effective for cervical cancer prevention in China. Additional triage with quality-assured performance could reduce overtreatment and remains highly cost-effective compared with current strategies.

Implementation of visual inspection with acetic acid and Lugol's iodine for cervical cancer screening in rural China.

OBJECTIVE: To address the value of visual inspection where HPV-based screening is not yet available, we evaluated the real-world effectiveness of visual inspection with acetic acid (VIA) and with Lugol's iodine (VILI) as a primary screening method for cervical cancer in rural China. METHODS: A total of 206 133 women aged 30-59 years received two rounds of VIA/VILI screening for cervical cancer in 2006-2010. Women with positive screening results underwent colposcopy and direct biopsy, and were treated if cervical intraepithelial neoplasia grade 2 or worse (CIN2+) was diagnosed. Clinical effectiveness of VIA/VILI was evaluated by process and outcome measures. RESULTS: The VIA/VILI positivity rate, biopsy rate and detection rate of CIN2+ in the second round were significantly lower than in the first round. The 2-year cumulative detection rate of CIN2+ varied from 0.53% to 0.90% among the four cohorts initiated in 2006, 2007, 2008, and 2009. The first round of screening detected 60%-83% of CIN2, 70%-86% of CIN3, and 88%-100% of cervical cancer. Over 92% of CIN2+ were found at the early stage. CONCLUSION: Multiple rounds of visual inspection with continuous training and quality assurance could act as a temporary substitutional screening method for cervical cancer in resource-restricted settings.

Efficacy of point-of-care thermal ablation among high-risk human papillomavirus positive women in China.

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.

Comparative performance evaluation of different HPV tests and triaging strategies using self-samples and feasibility assessment of thermal ablation in 'colposcopy and treat' approach: A population-based study in rural China.

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.

Clinical Performance of Human Papillomavirus Testing and Visual Inspection With Acetic Acid in Primary, Combination, and Sequential Cervical Cancer Screening in China.

BACKGROUND: World Health Organization guidelines recommend screening with human papillomavirus (HPV) testing followed by either treatment of all HPV-positives, or by visual inspection (VIA) for triage to treatment, citing insufficient evidence to recommend either strategy over the other. METHODS: We assessed VIA and HPV testing individually, in combination (HPV-VIA cotesting), and as triage models. Three thousand women were screened in Inner Mongolia, China, concurrently with HPV testing and VIA in a real population setting. Screen-positive women underwent colposcopy, and biopsy, if indicated. Accuracy of screening algorithms for cervical intraepithelial neoplasia grade 2 or higher (CIN-2+) was calculated after controlling for verification bias. HPV testing followed by VIA triage for CIN-2+ detection was compared with Hybrid Capture 2 viral loads triage, measured in relative light units/cutoff. RESULTS: CIN-2+ prevalence was 1.0%. Corrected sensitivity, false negative rate, and specificity for CIN-2+, respectively, for primary HPV testing were 89.7%, 10.3%, and 83.3%; 44.8%, 55.2%, and 92·3% for VIA; 93.1%, 6.9%, and 80.2% for HPV-VIA cotesting; and 41.4%, 58.6, and 95.4% for HPV with VIA triage scenarios. Using relative light units/cutoff of 5 or greater to triage HPV-positive women had twice the sensitivity as VIA triage, with comparable specificity for CIN-2+. CONCLUSIONS: When VIA performs relatively poorly and HPV testing is available, adding VIA to sequential (ie, HPV followed by VIA triage) or primary (HPV-VIA cotesting) screening does not significantly improve CIN-2+ detection beyond primary HPV screening alone. Sequential screening (ie, HPV followed by VIA triage) reduces sensitivity too low for population-based screening programs. The HPV viral loads could offer an alternative low-resource country triage strategy.

Expression of glucose transporter protein 1 and p63 in serous ovarian tumor.

AIM: It has been shown that glycolytic metabolism is increased in malignant cells. Cancer cell growth is an energy-related process supported by an increased glucose metabolism. In addition, p63, a known homolog of p53, is expressed predominantly in basal cell and squamous cell carcinomas. The purpose of this study was to evaluate the expression of glucose transporter protein 1 (GLUT1) and p63 in patients with serous ovarian tumor (benign, borderline and malignant) and study their close relationship with the malignant transformation of serous ovarian tumors. METHODS: Two hundred formalin-fixed, paraffin-embedded sections were immunostained with rabbit anti-GLUT1 polyclonal antibody and mouse anti-p63 monoclonal antibody using the streptavidin-biotin method. The samples were as follows: 40 normal ovarian tissues, 40 serous cystadenomas, 40 borderline serous cystadenomas and 80 serous cystadenocarcinomas were stained. RESULT: Normal ovarian tissues showed completely negative staining for GLUT1 and p63. However, from benign serious cystadenomas, borderline cystadenomas to cystadenocarcinomas, the expression of GLUT1 and p63 grew stronger (P < 0.05). Moreover, the intensity staining of GLUT1 maintained a significant association with the expression of p63 (P < 0.05). In χ²-test analysis, expression of borderline cystadenomas and cystadenocarcinomas, intraperitoneal implants, ascites, lymph node status and International Federation of Gynecology and Obstetrics (FIGO) stage and GLUT1 expression levels have an appalling significance (P < 0.05), while FIGO stage, intraperitoneal implants and lymph node status except patient age and ascites have a statistical significance with the expression of p63 levels (P < 0.05). CONCLUSION: Our findings show a progressive increase in the expression of GLUT1 and p63 from the benign serous cystadenomas, borderline cystadenomas to cystadenocarcinomas. Overexpression of GLUT1 and p63 are associated with the histology FIGO stage and metastasis of the tumors. These data suggested that the expression of GLUT1 and p63 may be closely related to the malignant transformation of serous ovarian tumors. However, the relative importance of GLUT1 and p63 in ovarian serous tumor development and tumorigenesis remains mostly unclear and awaits further investigation.

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

OBJECTIVES: To assess knowledge of HPV and attitudes towards HPV vaccination among the general female population, government officials, and healthcare providers in China to assist the development of an effective national HPV vaccination program. METHODS: A cross-sectional epidemiologic survey was conducted across 21 urban and rural sites in China using a short questionnaire. 763 government officials, 760 healthcare providers, and 11,681 women aged 15-59 years were included in the final analysis. Data were analyzed using standard descriptive statistics and logistic regression. RESULTS: Knowledge of HPV among the general female population was low; only 24% had heard of HPV. Less than 20% of healthcare providers recognized sexually naive women as the most appropriate population for HPV vaccination. There was high acceptance of the HPV vaccine for all categories of respondents. Only 6% of women were willing to pay more than US $300 for the vaccine. CONCLUSIONS: Aggressive education is necessary to increase knowledge of HPV and its vaccine. Further proof of vaccine safety and efficacy and government subsidies combined with increased awareness could facilitate development and implementation of HPV vaccination in China.

A multi-center survey of age of sexual debut and sexual behavior in Chinese women: suggestions for optimal age of human papillomavirus vaccination in China.

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.

[Human papillomavirus genotype distribution in invasive squamous cell carcinoma of the uterine cervix in Mongolian women in inner Mongolia autonomy region].

OBJECTIVE: To investigate the prevalence of human papillomavirus (HPV) and the HPV genotype distribution in invasive squamous cell carcinoma of the uterine cervix in the Mongolian women in Inner Mongolia autonomy region. METHODS: The prevalence data of HPV in our department were retrospectively reviewed. INNO-LiPA genotyping technique was used to detect HPV genotypes in the reserved carcinoma tissue specimens. RESULTS: Totally 63 tissue specimens were collected and detected. The prevalence of HPV was 93.7%. The positive rates of HPV among different clinical staging and different pathological grading were not significantly different (P >0.05). The prevalence of HPV16 was not significantly different among different age groups (P>0.05). HPV16 (69.8%), HPV18 (4.8%), HPV31 (4.8%), HPV39 (4.8%), and HPV52 (3.2%) were the 5 dominating HPV genotypes in all cases. CONCLUSIONS: HPV infection is closely correlated with invasive squamous cell carcinoma of the uterine cervix in Mongolia women. HPV16 is the most important genotype in invasive squamous cell carcinoma of the uterine cervix, followed by HPV18, 31, and 39. HPV infection dose not affect the progression and differentiation of invasive squamous cell carcinoma of the uterine cervix.