Cervical Cancer Screening via Visual Inspection With Acetic Acid and Lugol Iodine for Triage of HPV-Positive Women.

Importance: Limited evidence supports the performance of human papillomavirus (HPV) DNA testing as a primary screening method, followed by triage with visual inspection with acetic acid, in areas with limited health care resources, as suggested by the 2021 World Health Organization guidelines. Objective: To evaluate the performance of visual inspection with acetic acid and Lugol iodine as a triage method for detecting cervical precancerous lesions among HPV-positive women in 1 visit. Design, Setting, and Participants: This cohort study examined the implementation of a government-led cervical cancer screening program conducted from January 1, 2016, to December 31, 2020, in Ordos City, China. Female residents, aged 35 to 64 years, who understood the screening procedures and voluntarily participated were included in the study. Women were excluded if they reported never having had sexual intercourse, were pregnant, had a hysterectomy, or had ever undergone treatment for cervical lesions. Statistical analysis was conducted from December 2022 to December 2023. Exposures: The program used the careHPV DNA assay as the primary screening method, and immediate triage was performed by visual inspection if HPV screening results were positive, with a 5-year screening interval. A colposcopy was performed for the women who had suspected cancer on visual inspection results or who were HPV positive and had abnormal visual inspection results, all in 1 visit. Main Outcomes and Measures: The rate of compliance with colposcopy and the detection rate of cervical intraepithelial neoplasia grade 2 or higher (CIN2+). Results: The study included 187 863 women (median age, 46 years [IQR, 40-52 years]) who participated in the program and had valid HPV test results. The overall prevalence of HPV positivity was 12.8% (24 070 of 187 863), and the adherence to triage with visual inspection among HPV-positive women was 93.9% (22 592 of 24 070). Among HPV-positive women, the rate of compliance with colposcopy was 65.6% (2714 of 4137), and the CIN2+ detection rate was 2.8% (643 of 22 592). Conclusions and Relevance: The findings of this cohort study suggest that the implementation of HPV testing, visual inspection, and colposcopy within 1 visit may mitigate losses to follow-up, detect precancerous lesions, and hold significant implications for screening in comparable areas with limited health care resources.

Involvement in treatment decision-making and self-reported efficacy among patients with advanced colorectal cancer: a nationwide multi-center cross-sectional study.

Introduction: This cross-sectional study evaluated the involvement of patients with advanced colorectal cancer (CRC) in treatment decision-making, assessed the treatment efficacy according to their self-reports, and investigated the influencing factors. Methods: Patients with advanced CRC were recruited from 19 hospitals from March 2020 to March 2021 by a multi-stage multi-level sampling method. A self-designed questionnaire was used to collect demographic and clinical characteristics, involvement of CRC patients in treatment decision-making, treatment methods, and self-reported efficacy. Univariate and unordered multinomial logistic regression analyses were used to evaluate the factors affecting the involvement in treatment decision-making and self-reported efficacy. Results: We enrolled 4533 patients with advanced CRC. The average age at diagnosis was 58.7 ± 11.8 years. For the treatment method, 32.4% of patients received surgery combined with chemotherapy, 13.1% of patients underwent surgery combined with chemotherapy and targeted therapy, and 9.7% of patients were treated with surgery alone. For treatment decision-making, 7.0% of patients were solely responsible for decision-making, 47.0% of patients shared treatment decision-making with family members, 19.0% of patients had family members solely responsible for treatment decision-making, and 27.0% of patients had their physicians solely responsible for treatment decision-making. Gender, age, education level, family income, marital status, treatment cost, hospital type, and treatment method were significantly associated with the involvement of patients in treatment decision-making. A total of 3824 patients submitted self-reported efficacy evaluations during treatment. The percentage of patients with good self-reported efficacy was 76.5% (for patients treated for the first time), 61.7% (for patients treated for the second time), and 43.2% (for patients treated after recurrence and metastasis), respectively. Occupation, education level, average annual family income, place of residence, time since cancer diagnosis, hospital type, clinical stage, targeted therapy, and involvement in treatment decision-making were the main influencing factors of self-reported efficacy of treatment. Discussion: Conclusively, CRC patients are not highly dominant in treatment decision-making and more likely to make treatment decisions with their family and doctors. Timely and effective communication between doctors and patients can bolster patient involvement in treatment decision-making.

Correction: Unassisted Clinicians Versus Deep Learning-Assisted Clinicians in Image-Based Cancer Diagnostics: Systematic Review With Meta-analysis.

[This corrects the article DOI: 10.2196/43832.].

Artificial intelligence in colposcopic examination: A promising tool to assist junior colposcopists.

Introduction: Well-trained colposcopists are in huge shortage worldwide, especially in low-resource areas. Here, we aimed to evaluate the Colposcopic Artificial Intelligence Auxiliary Diagnostic System (CAIADS) to detect abnormalities based on digital colposcopy images, especially focusing on its role in assisting junior colposcopist to correctly identify the lesion areas where biopsy should be performed. Materials and methods: This is a hospital-based retrospective study, which recruited the women who visited colposcopy clinics between September 2021 to January 2022. A total of 366 of 1,146 women with complete medical information recorded by a senior colposcopist and valid histology results were included. Anonymized colposcopy images were reviewed by CAIADS and a junior colposcopist separately, and the junior colposcopist reviewed the colposcopy images with CAIADS results (named CAIADS-Junior). The diagnostic accuracy and biopsy efficiency of CAIADS and CAIADS-Junior were assessed in detecting cervical intraepithelial neoplasia grade 2 or worse (CIN2+), CIN3+, and cancer in comparison with the senior and junior colposcipists. The factors influencing the accuracy of CAIADS were explored. Results: For CIN2 + and CIN3 + detection, CAIADS showed a sensitivity at ~80%, which was not significantly lower than the sensitivity achieved by the senior colposcopist (for CIN2 +: 80.6 vs. 91.3%, p = 0.061 and for CIN3 +: 80.0 vs. 90.0%, p = 0.189). The sensitivity of the junior colposcopist was increased significantly with the assistance of CAIADS (for CIN2 +: 95.1 vs. 79.6%, p = 0.002 and for CIN3 +: 97.1 vs. 85.7%, p = 0.039) and was comparable to those of the senior colposcopists (for CIN2 +: 95.1 vs. 91.3%, p = 0.388 and for CIN3 +: 97.1 vs. 90.0%, p = 0.125). In detecting cervical cancer, CAIADS achieved the highest sensitivity at 100%. For all endpoints, CAIADS showed the highest specificity (55-64%) and positive predictive values compared to both senior and junior colposcopists. When CIN grades became higher, the average biopsy numbers decreased for the subspecialists and CAIADS required a minimum number of biopsies to detect per case (2.2-2.6 cut-points). Meanwhile, the biopsy sensitivity of the junior colposcopist was the lowest, but the CAIADS-assisted junior colposcopist achieved a higher biopsy sensitivity. Conclusion: Colposcopic Artificial Intelligence Auxiliary Diagnostic System could assist junior colposcopists to improve diagnostic accuracy and biopsy efficiency, which might be a promising solution to improve the quality of cervical cancer screening in low-resource settings.

Unassisted Clinicians Versus Deep Learning-Assisted Clinicians in Image-Based Cancer Diagnostics: Systematic Review With Meta-analysis.

BACKGROUND: A number of publications have demonstrated that deep learning (DL) algorithms matched or outperformed clinicians in image-based cancer diagnostics, but these algorithms are frequently considered as opponents rather than partners. Despite the clinicians-in-the-loop DL approach having great potential, no study has systematically quantified the diagnostic accuracy of clinicians with and without the assistance of DL in image-based cancer identification. OBJECTIVE: We systematically quantified the diagnostic accuracy of clinicians with and without the assistance of DL in image-based cancer identification. METHODS: PubMed, Embase, IEEEXplore, and the Cochrane Library were searched for studies published between January 1, 2012, and December 7, 2021. Any type of study design was permitted that focused on comparing unassisted clinicians and DL-assisted clinicians in cancer identification using medical imaging. Studies using medical waveform-data graphics material and those investigating image segmentation rather than classification were excluded. Studies providing binary diagnostic accuracy data and contingency tables were included for further meta-analysis. Two subgroups were defined and analyzed, including cancer type and imaging modality. RESULTS: In total, 9796 studies were identified, of which 48 were deemed eligible for systematic review. Twenty-five of these studies made comparisons between unassisted clinicians and DL-assisted clinicians and provided sufficient data for statistical synthesis. We found a pooled sensitivity of 83% (95% CI 80%-86%) for unassisted clinicians and 88% (95% CI 86%-90%) for DL-assisted clinicians. Pooled specificity was 86% (95% CI 83%-88%) for unassisted clinicians and 88% (95% CI 85%-90%) for DL-assisted clinicians. The pooled sensitivity and specificity values for DL-assisted clinicians were higher than for unassisted clinicians, at ratios of 1.07 (95% CI 1.05-1.09) and 1.03 (95% CI 1.02-1.05), respectively. Similar diagnostic performance by DL-assisted clinicians was also observed across the predefined subgroups. CONCLUSIONS: The diagnostic performance of DL-assisted clinicians appears better than unassisted clinicians in image-based cancer identification. However, caution should be exercised, because the evidence provided in the reviewed studies does not cover all the minutiae involved in real-world clinical practice. Combining qualitative insights from clinical practice with data-science approaches may improve DL-assisted practice, although further research is required. TRIAL REGISTRATION: PROSPERO CRD42021281372; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=281372.

Performance of Human Gene EPB41L3 and HPV 16/18 Viral DNA Methylation to Triage hrHPV-Positive Women.

More evidence from population-based cohort studies is required to confirm the application of methylation-based biomarkers in real-world settings. The cross-sectional and 24-month cumulative triage performance of a novel methylation assay targeting the host gene EPB41LE and HPV16/18 DNA L1/L2 regions among hrHPV-positive women was evaluated based on a population-based cohort study from China. Overall methylation positivity was 12.4% among hrHPV-positive women. Methylation-positive women had significantly higher risks of hrHPV persistence at 12M and 24M follow-up (RR12M = 1.9, 95%CI: 1.5-2.6 and RR24M = 1.7, 95%CI: 1.2-2.5). For CIN2+, cross-sectional triage sensitivity of methylation was similar to HPV16/18 (70.6% vs. 64.7%, pexact = 1.000), but was lower than cytology (94.1%), although not significantly (pexact = 0.213). The specificity (91.2%) of methylation was significantly higher than other triage methods (p < 0.001 for all). The longitudinal sensitivity of methylation over 24M follow-up was 56.0%, lower (but not significantly so) than HPV16/18 (64.0%, pexact = 0.688) and cytology (76.0%, pexact = 0.125). Methylation testing showed high positive predictive values for CIN2+ (41.4% at baseline, 50.0% at 24-month), while the CIN2+ risk of methylation negative women (cNPV) remained considerable (2.5% at baseline, 6.9% at 24-month). Study findings indicate that methylation has better specificity and predictive values for the presence or development of cervical precancer and might therefore be considered for the strategy of HPV screening and methylation triage followed by immediate treatment of triage-positive women and delayed follow-up of hrHPV-positive/methylation-negative women.

Accuracy and effectiveness of HPV mRNA testing in cervical cancer screening: a systematic review and meta-analysis.

BACKGROUND: Cervical cancer screening tests that identify DNA of the main causal agent, high-risk human papillomavirus (HPV) types, are more protective than cervical cytology. We systematically reviewed the literature to assess whether tests targeting high-risk HPV (hrHPV) mRNA are as accurate and effective as HPV DNA-based screening tests. METHODS: We did a systematic review to assess the cross-sectional clinical accuracy to detect cervical intraepithelial neoplasia of grade 2 or worse (CIN2+) or 3 or worse (CIN3+) of hrHPV mRNA versus DNA testing in primary cervical cancer screening; the longitudinal clinical performance of cervical cancer screening using hrHPV mRNA versus DNA assays; and the clinical accuracy of hrHPV mRNA testing on self-collected versus clinician-collected samples. We identified relevant studies published before Aug 1, 2021, through a search of Medline (PubMed), Embase, and CENTRAL. Eligible studies had to contain comparative data addressing one of our three clinical questions. Aggregated data were extracted from selected reports or requested from study authors if necessary. QUADAS and ROBINS-1 tools were used to assess the quality of diagnostic test accuracy studies and cohort studies. To assess cross-sectional clinical accuracy of mRNA testing versus DNA testing and clinical accuracy of hrHPV mRNA testing on self-collected versus clinician collected samples, we applied meta-analytical methods for comparison of diagnostic tests. To assess the longitudinal clinical performance of cervical cancer screening using hrHPV mRNA versus DNA assays, we compared the longitudinal sensitivity of mRNA tests and validated DNA tests for CIN3+ and the relative detection of CIN3+ among women who screened negative for hrHPV mRNA or DNA (both used as measures of safety) at baseline and pooled estimates by years of follow-up. A random-effect model for pooling ratios of proportions or risks was used to summarise longitudinal performance. FINDINGS: For the hrHPV mRNA testing with APTIMA HPV Test (APTIMA), the cross-sectional accuracy could be compared with DNA assays on clinician-collected samples in eight studies; longitudinal performance was compared in four studies; and accuracy on self-samples was assessed in five studies. Few reports were retrieved for other mRNA assays, precluding their evaluation in meta-analyses. Compared with validated DNA assays, APTIMA was similarly sensitive (relative sensitivity 0·98 [95% CI 0·95-1·01]) and slightly more specific (1·03 [1·02-1·04]) for CIN2+. The relative sensitivity for CIN3+ was 0·98 (95% CI 0·95-1·01). The longitudinal relative sensitivity for CIN3+ of APTIMA compared with DNA assays assessed over 4-7 years ranged at the study level from 0·91 to 1·05 and in the pooled analysis between 0·95 and 0·98, depending on timepoint, with CIs including or close to unity. The detection rate ratios between 4 and 10 years after baseline negative mRNA versus negative DNA screening were imprecise and heterogeneous among studies, but summary ratios did not differ from unity. In self-collected samples, APTIMA was less sensitive for CIN2+ (relative cross-sectional sensitivity 0·84 [0·74-0·96]) but similarly specific (relative specificity 0·96 [0·91-1·01]) compared with clinician-collected samples. INTERPRETATION: HrHPV RNA testing with APTIMA had similar cross-sectional sensitivity for CIN2+ and CIN3+ and slightly higher specificity than DNA tests. Four studies with 4-7 years of follow-up showed heterogeneous safety outcomes. One study with up to 10 years of follow-up showed no differences in cumulative detection of CIN3+ after negative mRNA versus DNA screening. APTIMA could be accepted for primary cervical cancer screening on clinician-collected cervical samples at intervals of around 5 years. APTIMA is less sensitive on self-collected samples than clinician-collected samples. FUNDING: Horizon 2020 Framework Programme for Research and Innovation of the European Commission, through the RISCC Network, WHO, Haute Autorité de la Santé, European Society of Gynaecological Oncology, and the National Institute of Public Health and the Environment.

Cervical cancer burden, status of implementation and challenges of cervical cancer screening in Association of Southeast Asian Nations (ASEAN) countries.

Multiple barriers impede the transformation of evidence-based research into implementation of cervical cancer screening in ASEAN countries. This review is the first of its kind to show the disease burden of cervical cancer, progress till date to implement screening and corresponding challenges, and propose tailored solutions to promote cervical cancer prevention in ASEAN. In 2020, approximately 69 000 cervical cancer cases and 38 000 deaths happened in ASEAN, and more than 44% and 63% increases on new cases and deaths are expected in 2040. Only four countries have initiated population-based cervical cancer screening programs, but the participation rate is less than 50% in some countries and even lower than 10% in Myanmar and Indonesia. Inequity and unavailability in service delivery, lack of knowledge and awareness, limited follow-up and treatment capacity, and funding sustainability affect successful scale-up of cervical cancer screening most in ASEAN. Implementing HPV detection-based primary screening, appropriate management of screen-positives, enhancing health education, integrating health services can accelerate reduction of cervical cancer burden in ASEAN. Achieving high screening coverage and high treatment compliance will help ASEAN countries remain aligned to cervical cancer elimination strategies.

Human papillomavirus distribution and cervical cancer epidemiological characteristics in rural population of Xinjiang, China.

BACKGROUND: Cervical cancer remains a major public health issue for the Uyghur women and other women living mainly in rural areas of Xinjiang. This study aims to investigate the distribution of human papillomavirus (HPV) infection and cervical cancer in rural areas of Xinjiang, China. METHODS: Cervical cancer screening was performed on rural women aged 35 to 64 years from Xinjiang, China in 2017 through gynecological examination, vaginal discharge smear microscopy, cytology, and HPV testing. If necessary, colposcopy and biopsy were performed on women with suspicious or abnormal screening results. RESULTS: Of the 216,754 women screened, 15,518 received HPV testing. The HPV-positive rate was 6.75% (1047/15,518). Compared with the age 35-44 years group, the odds ratios (ORs) of HPV positivity in the age 45-54 years and 55-64 years groups were 1.18 (95% confidence interval [CI]: 1.02-1.37) and 1.84 (95% CI: 1.53-2.21), respectively. Compared with women with primary or lower education level, the ORs for HPV infection rates of women with high school and college education or above were 1.37 (95% CI: 1.09-1.72) and 1.62 (95% CI: 1.23-2.12), respectively. Uyghur women were less likely to have HPV infection than Han women, with an OR (95% CI) of 0.78 (0.61-0.99). The most prevalent HPV types among Xinjiang women were HPV 16 (24.00%), HPV 33 (12.70%), and HPV 52 (11.80%). The detection rate of cervical intraepithelial neoplasia (CIN)2+ was 0.14% and the early diagnosis rate of cervical cancer was 85.91%. The detection rates of vaginitis and cervicitis were 19.28% and 21.32%, respectively. CONCLUSIONS: The HPV infection rate in Xinjiang is low, but the detection rate of cervical cancer and precancerous lesions is higher than the national average level. Cervical cancer is a prominent public health problem in Xinjiang, especially in southern Xinjiang.

2020 list of human papillomavirus assays suitable for primary cervical cancer screening.

BACKGROUND: Only clinically validated HPV assays can be accepted in cervical cancer screening. OBJECTIVES: To update the list of high-risk HPV assays that fulfil the 2009 international validation criteria (Meijer-2009). DATA SOURCES: PubMed/Medline, Embase, Scopus, references from selected studies; published in January 2014 to August 2020. STUDY ELIGIBILITY CRITERIA: HPV test validation studies and primary screening studies, involving testing with an index HPV test and a comparator HPV test with reporting of disease outcome (occurrence of histologically confirmed cervical precancer; CIN2+). PARTICIPANTS: Women participating in cervical cancer screening. INTERVENTIONS: Testing with an index and a comparator HPV test of clinician-collected cervical specimens and assessment of disease outcome (

Clinical evaluation of p16INK4a immunocytology in cervical cancer screening: A population-based cross-sectional study from rural China.

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.

Effect of Sequential Rounds of Cervical Cancer Screening on Management of HPV-positive Women: A 15-year Population-based Cohort Study from China.

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.

[Genotype distribution and behavioral risk factor analysis of human papillomavirus infection among Kazak women in Xinjiang Uygur Autonomous Region].

Objective: To investigate the prevalence and genotype distribution of high-risk human papillomavirus (HR-HPV) and the correlation between cervical lesions and analyze the risk factors for HR-HPV infection. Methods: In June 2018, a population-based study for cervical cancer screening in Tuoli county of Xinjiang Uygur Autonomous Region was conducted. A total of 2 000 Kazak women aged 25-64 years were included in the study. Three cervical exfoliated cells samples were collected from them for careHPV, PCR HPV, p16(INK4a), and liquid-based cytology (LBC) tests. Women with any positive test were referred for colposcopy with biopsies taken at abnormal sites. Histo-pathological diagnoses were used as the gold standard. Results: The overall prevalence of HPV was 14.55%, among which the infection rate of HR-HPV was 12.90%, which was even higher in the 50-54 years age group. The most prevalent genotypes of HR-HPV were HPV16 (2.80%), HPV51(2.35%), HPV52 (1.70%), HPV56 (1.50%), and HPV39 (1.20%). The most common HPV infection was a single infection (71.48%). In the age group of 50-54 years, the multiple infection rates were higher, with the majority of double infection (69.88%), and HPV42 and 56 were the most common co-infection types. HPV16 (31.82%), HPV51 (27.27%) and HPV18 (13.64%) were higher in cervical intraepithelial neplasia grade 1, HPV16 (57.14%) was higher in cervical intraepithelial neplasia grade 2, and HPV16 (55.56%) and HPV18 (33.33%) were higher in cervical intraepithelial neplasia grade 3 or worse. Results from the multivariate logistic regression analysis showed that higher education, menopause, and syphilis infection increased the HPV infection. Conclusions: The most common prevalence genotypes of HR-HPV among Kazak women were HPV16, HPV51, and HPV52. The infection rate of HR-HPV among Kazak women was correlated with education level, menopausal status, and syphilis infection. Measures should be taken targeting high-risk factors. This result suggests that STD patients and women aged 50 and above should be encouraged for screening.

Triage options to manage high-risk human papillomavirus-positive women: A population-based cross-sectional study from rural China.

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.

Triage of HPV-positive women in Norway using cytology, HPV16/18 genotyping and HPV persistence.

In a Norwegian pilot, triage of high-risk human papillomavirus (hrHPV)-positive women with reflex cytology followed by hrHPV testing 12 months later, yielded 82% of women referred to colposcopy and 24% with CIN3+. A policy stratified by the presence of HPV16/18 would be more efficient (66% referred to colposcopy) at the expense of small losses in the detection of precancer.

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.

Outcomes in women with biopsy-confirmed cervical intraepithelial neoplasia grade 1 or normal cervix and related cofactors: A 15-year population-based cohort study from China.

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.

Eight-type human papillomavirus E6/E7 oncoprotein detection as a novel and promising triage strategy for managing HPV-positive women.

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.

Training Future Leaders: Experience from China-ASEAN Cancer Control Training Program.

Cancer care professionals are pivotal in translating the knowledge into action in the continuum of cancer control process. Unfortunately, in China and the Association of South-east Asian Nations (ASEAN), limited training opportunities are available for health professionals in the area of cancer prevention and control. Therefore, the Cancer Hospital, Chinese Academy of Medical Sciences (CICAMS), and the International Agency for Research on Cancer (IARC) collaboratively designed and held the China-ASEAN Cancer Control and Prevention Training Program to provide continuing education opportunities for cancer professionals from China and ASEAN countries. The aim of this article is to report on the effectiveness and quality of the program and share our experience. A total of 36 participants from 12 countries completed the whole course including 1-month online learning and 1-week face-to-face workshop and cancer control facility tour in October 2017. After completion of the program, all participants were invited to fill out a questionnaire and to provide their comments on the training course. Out of 36 participants, 33 completed the evaluation form and they rated the training course highly in terms of satisfaction, value, and likelihood of recommending it to other colleagues. Additionally, all participants provided very detailed and practical comments on the course. Such an intensive, short-term, and comprehensive training program is expected to help participants establish a broader view of cancer prevention and control within the wider health services and be involved in national cancer control programs in a more efficient way. This training course could serve as a model for other institutes dedicated to nurturing future leaders in cancer control.

Clinical Value of Human Papillomavirus E6/E7 mRNA Detection in Screening for Cervical Cancer in Women Positive for Human Papillomavirus DNA or.

BACKGROUND: The detection of human papillomavirus (HPV) E6/E7 mRNA indicates a risk of further deterioration in cervical lesions. We explored the clinical value of HPV E6/E7 mRNA detection in cervical cancer screening in women positive for HPV or with abnormal thin-prep cytology test (TCT) results in the Xinjiang region of China. METHODS: A total of 6,800 women were screened in our hospital for cervical cancer by both TCT and HPV DNA testing from August 2013 to June 2015. Of these, 197 had abnormal cytological or HPV test results and subsequently underwent HPV E6/E7 mRNA detection and histopathological examination, while 101 underwent an HPV DNA typing test. Using pathological results as the gold standard, we compared the accuracies of HPV E6/E7 mRNA detection or HPV DNA type testing alone, in parallel, and in series for diagnosing high-grade cervical lesions. RESULTS: Pathological examination revealed 80 cases of chronic cervicitis, 16 cases of cervical intraepithelial neoplasia (CIN)-I, 50 cases of CIN-II-III, and 51 cases of cervical cancer. The area under the receiver operating characteristic (ROC) curve (AUC) for diagnosing high-grade cervical lesions by HPV E6/E7 mRNA detection was 74.95% (sensitivity, 85.15%; specificity, 66.67%; Youden index, 0.139; positive predictive value, 72.9%; negative predictive value, 81.0%; positive likelihood ratio, 2.555; negative likelihood ratio, 0.222; and post-test probability, 72.9%). CONCLUSIONS: HPV E6/E7 mRNA detection is superior to HPV DNA type testing for diagnosing high-grade cervical lesions.