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PURPOSE This ongoing trial is comparing the efficacy and safety of three ablation treatments for cervical intraepithelial neoplasia grade 2 or higher. Here, we present early data regarding pain, side effects, and acceptability of CO2 gas-based cryotherapy (CO2), nongas cryotherapy, and thermal ablation (TA). Efficacy results are expected to become available in late 2023. MATERIALS AND METHODS This noninferiority randomized trial is taking place in El Salvador, China, and Colombia. Patients are 1,152 eligible women with biopsy-confirmed cervical intraepithelial neoplasia grade 2 or higher who will receive one of three ablation treatments. Pain is measured before, during, and after treatment with a visual analog scale (1-10). Side effects and acceptability are assessed at 6 weeks. RESULTS To date, 1,024 of 1,152 (89%) women were randomly assigned to treatment. The median pain level was higher during TA (4, IQR = 4) than CO2 (2, IQR = 4) or nongas cryotherapy (2, IQR = 4) ( P < .01, range: 0-10). The most common post-treatment symptom was watery discharge, reported by 97.9% of women, and it lasted longer in the CO2 group than the other two treatments (in days, median [IQR]: CO2 = 20[20], nongas cryotherapy = 15[10], TA = 18[15], P < .01). Bleeding was reported more frequently in women treated with TA (27.6%) than CO2 (17.5) or nongas cryotherapy (18.7%) ( P < .01). The majority of patients reported being very satisfied with the treatment they received at 6 weeks (91%) and again at 12 months post-treatment (97%). CONCLUSION Despite differences in pain and side effects across ablation treatments, all were safe and highly acceptable to patients. In addition to efficacy, considerations such as cost and portability may be more significant in choosing a treatment method.

Objective To investigate the epidemiological characteristics of high-risk human papillomavirus(HR-HPV) infection based on vaginal self-collected samples. Study Design and Setting The pooled data of 3045 self-collected samples used for the analysis derived from four previous studies on cervical cancer screening(The Chinese Multi-Center Screening Trial, CHIMUST; The Shenzhen Cervical Cancer Screening Trial-2, SHENCCAST-2; The Chinese Cervical Cancer Prevention Study, CHIPCAPS; Pingshan trial, PINGSHAN)conducted across China by our team since 2011. These cases were evaluated for HR-HPV type prevalence relative to lesion grade and age. The occurrence of cervical intraepithelial neoplasia(CIN) with specific HPV types and the influence of co-infection is explored. Results The top three most common genotypes among the HR-HPV positives were HPV-52(23.4%), HPV-16(18.0%), and HPV-58(15.50%). For women with CIN2+, the most frequent genotypes were HPV-16, 58, 52, and 18 in sequence. HPV-16 accounted for the majority of CIN2/CIN3/Ca with attribution rate of 23.86%, 44.78% and 50.00% respectively. HPV-58 accounted for 19.48%, 16.79% and 13.46% respectively. CIN2+ was found in the following types most frequently: HPV-16(31.23%), HPV-33(24.03%), HPV-58(18.41%), HPV-31(11.76%), HPV-18(7.75%), and HPV-52(7.30%). HPV-16 showed preference for co-infection with HPV-52 and HPV-58. Conclusion The prevalence of HR-HPV infection based on self-sampling among women in China exhibited some unique epidemiologic features.

Objective Self-sampling for human papillomavirus (HPV) testing is an effective option to increase the cervical screening coverage. How to best triage HPV-positive self-samples remains controversial. Here, we evaluated the performance of a novel p16INK4a immunocytology approach (p16) and HPV genotyping in triaging HPV-positive self-samples. Methods A cohort of 73699 women were screened via SeqHPV assay on self-samples. HPV-positive women who met any sequential positive result of HPV16/18 or VIA or p16 were referred for colposcopy. A triage strategy was considered favorable if the NPV for CIN3+ was ≥98%, combined with an improvement of sensitivity and specificity in comparison to the comparator, being the ‘ASC-US+’ triage and the guideline strategy (HPV16/18+ or ASC-US+). Results A total of 3510 HPV-positive women were included, 422 (12.0%) CIN2+ and 247 (7.0%) CIN3+ were identified. The positivity of p16 and ASC-US+ were 36.3% and 22.2%, respectively. p16 was more sensitive and less specific than ASC-US+ (P Conclusions Our findings indicate the promising utility of p16 immunocytology via adjusting the staining score or serving as an ancillary tool to liquid-based cytology or combining with genotyping for the triage of HPV-positive self-samples, which promotes the precise screening of cervical cancer.

ObjectiveTo validate the HPV viral loads that are reflected by the cycle threshold values of Cobas4800 as the viral load indicators by verifying the consistency of the viral loads per unit (10,000 cells) from the BMRT assay.MethodsThe analysis is based on data from the Chinese Multi-Center Screening Trial (CHIMUST). The cases included in the analysis are all positive for physician-collected hrHPV on SeqHPV and/or Cobas4800 or negative for hrHPV but abnormal in cytology (≥LSIL), and some cases selected by nested case-control randomization from those negative for physician-collected hrHPV and cytology. With HPV testing results and relevant Ct values from Cobas4800 available, we tested the entire sample set with the BMRT HPV testing assay and analyzed their agreement with Cobas4800, followed by a comparison of the CtV from Cobas4800 and viral loads (lg) from BMRT by lesion grade.ResultsWe included 4,485 women (mean age: 45.4 years) in the study, and 4,290 had complete data. The consistency of genotypes from Cobas4800 and BMRT for hrHPV, HPV-16, HPV-18, and 12-HPV pools was 94.9% (4070/4290, Kappa = 0.827), 99.1% (4251/4290, Kappa = 0.842), 99.6% (4,273/4,290, Kappa = 0.777), and 95.3% (4,089/4,290, Kappa = 0.821), respectively. Further analysis shows that any inconsistency between the two assays is likely among samples with comparatively lower viral loads. When analyzing per lesions of CIN2+ and CIN3+, the CtV from Cobas4800 and VL (lg) from BMRT are highly correlated inversely and follow the linear regression for HPV16 and 12-HPV pool (Pearson's or Spearman's correlation coefficient (r): In CIN3+, r HPV16 = −0.641, P < 0.001; r 12−HPVpool = −0.343, P = 0.109; In CIN2+, r HPV16 = −0.754, P < 0.001; r 12−HPVpool = −0.429, P < 0.001).ConclusionThe CtV from Cobas4800 and the viral loads (lg) of per unit cells from the BMRT are well correlated for lesion grading when tested on physician-collected samples. Cobas-CtV is worthy of further study for clinical application.

Aim To compare thermocoagulation and cryotherapy for treatment of high‐grade cervical intraepithelial neoplasia (CIN). Methods From May 2017 to May 2018, women with CIN2/3 were randomized to thermocoagulation or cryotherapy at Peking University Shenzhen Hospital. Follow‐up at 4 and 8 months included cytology and human papillomavirus (HPV) testing. Women who were HPV‐positive or had atypical squamous cells of undetermined significance or higher‐grade disease underwent colposcopy/biopsy. Results Among 149 women enrolled, 74 were randomized to thermocoagulation, and 75 to cryotherapy (excluded four were immediately referred for thermocoagulation due to large lesions). At follow‐up, there was no difference between the thermocoagulation and cryotherapy groups in HPV‐negative (4/8 months: 72.5%/86.2% vs 68.6%/80.6%) and pathology‐negative (97.1%/98.5% vs 94.3%/92.3%) rates (all P > 0.05). The cytology‐negative rate was similar for thermocoagulation and cryotherapy at 4 months (79.7% vs 78.9%, P > 0.05), but higher for thermocoagulation at 8 months (100% vs 88.7%, P

Purpose When used for cervical cancer primary screening, liquid-based cytology (LBC) has a high specificity but a low sensitivity. For histological diagnosis of high-grade lesions, p16INK4a immunostaining has proven to be useful. Therefore, our objective was to evaluate the use of p16INK4a immuno-cytology as a primary screen and a secondary screen after primary high-risk human papillomavirus (hrHPV) screening or LBC screening. Methods A total of 1197 cytology slides were immuno-stained using automatic p16INK4a staining system (PathCIN®p16INK4a) in two studies from cervical screening programs. In the primary screening study, 875 slides were randomly selected and analyzed for p16INK4a. In the secondary screening study, 322 of the remaining slides were chosen by virtue of being HPV 16/18+, other hrHPV+/LBC≥ASC-US, or HPV-negative/LBC ≥LSIL. The sensitivity and specificity for detection of cervical intraepithelial neoplasia 2/3 or worse (CIN2+/CIN3+) were compared based on p16INK4a, LBC and HPV test results. Results In combining two studies, there were 431 cases with biopsy pathology. They included 83 cases with CIN2+ and 41 cases with CIN3+. The p16 positivity rate increased with pathologic and cytologic severity (P

Objective To verify the association of high-risk human papillomavirus (hrHPV) viral load reflected by cycle threshold (Ct) values from HPV testing on Cobas4800 assay with the histologic grades of cervical lesions via analysis on the combined data from two cervical cancer screening trials and to explore the referability of Ct values in management of the abnormalities from cervical cancer primary screening. Methods We analyzed the data from Chinese Multi-Center Screening Trial (CHMUST) and BUJI Cervical Cancer Screening Study Project (BUJI Study). All data to be analyzed in this paper were related to provider-collected samples. One-way ANOVA was performed to compare the Ct values among different histological groups, and Kendall’s tau-b correlation was applied to examine the association between Ct values and cervical lesion grades. The stepwise incidence of CIN2+ and CIN3+ in every 100 HPV positive individuals were calculated according to the descending of the genotype specific Ct values. The highest Ct values related to CIN3+ incidence rate 4% (or 25%) were used as the cutoffs to distinguish low-Ct value cases from the high-Ct value ones. Results A total of 1376 women in CHUMUST and BUJI Study who were aged 30–59 and positive of hrHPV for provider-collected samples on Cobas4800 with complete data in terms of the relevant Ct values (CtV) and the histological diagnosis were included for analysis. Our data showed significant difference among different histological grades of cervical lesions in the CtV of hrHPV, HPV16-plus (positive of HPV16 only or HPV16 plus 18 and/or pooled 12-HPV), and pooled 12-HPV (P P > 0.05). The CIN2+ or CIN3+ incidence per 100 positives significantly increased corresponding to the descending of the CtV of hrHPV, HPV16-plus and pooled 12-HPV. Compared with high-CtV groups (CtV > 33.2 for hrHPV, CtV > 29.6 for pooled 12-HPV), the relevant risks (RRs) of CIN2+ for hrHPV and pooled 12-HPV positive groups with low-CtV (CtV ≤ 33.2 and ≤ 29.6, respectively) were 3.2 (95%CI 2.18–4.80) and 2.3 (95%CI 1.50–3.45). Similarly, the RRs of CIN3+ for hrHPV and pooled 12-HPV positive groups with low-CtV were 6.5 (95%CI 2.83–14.80) and 2.7 (95%CI 1.15–6.39), respectively. The RRs of CIN2+ for medium- (30.3 37.4) groups, and the CIN3+ incidence in low-CtV value group was nine-fold higher of that in medium-CtV ones [RRs, 9.0 (95%CI 2.89–28.10)]. In comparing with the algorithms of “HPV16-plus/18-plus + cytology ≥ ASCUS for pooled 12-HPV”, triage algorithm “HPV16-plus/18-plus + Ct value ≤ 33.2 for pooled 12-HPV” could achieve a comparable sensitivity of 93.2%. Conclusion HPV viral loads reflected by Ct values for hrHPV, HPV16-plus and pooled 12-HPV from Cobas4800 HPV testing were directly associated with the severity of cervical lesions. A lower HPV genotype-specific Ct value prompted a significantly high CIN3+ risk of 4% or higher in women positive of hrHPV, HPV16-plus or pooled 12-HPV, indicating that HPV viral load reflected by Ct values on Cobas4800 may be a promising risk indicator in management of abnormalities from primary cervical cancer screening.

BackgroundThe disparities of hr-HPV infection among races/ethnicities have not been fully discussed. This study aimed to investigate the difference of hr-HPV infection between Chinese Han and Mongols minority women in Inner Mongolia.MethodsGenotyping and histopathology data of Chinese Han and Mongols minority women in Inner Mongolia from Chinese Multi-Center Screening Trial were used to analyze the hr-HPV prevalence, and type-specific distribution in abnormal pathology results.ResultsThe hr-HPV infection rates of Han women was 15.9% while of Mongols was 21.6% (P < 0.001). The most prevalent genotypes in Han women were ranked as HPV-16,−52,−18/-58,−31/-39, and−59 while in Mongols were−16,−31,−58,−18 and−52. When analyzing the age-specific of hr-HPV infection, two peaks were found at age of 40–44 (20.5%) and 55–59 (23.5%) years in Han women while three peaks were observed at age of 30–34 (22.1%), 45–49 (22.9%), and 55–59 (31.8%) years, respectively, in Mongols. HPV-16 accounting for 62.5 and 53.8% of the CINII+ in Han and Mongols, respectively.ConclusionThe prevalence of hr-HPV was significantly different between the Han and Mongols minority women in Inner Mongolia, races/ethnicities background should be taken into consideration for the refinement of cervical cancer screening strategies and vaccine implementation in China.

Background Self-sampling for human papillomavirus (HPV) testing is a feasible option to improve the cervical screening coverage. However, an ideal triage method for HPV-positive self-samples does not yet exist. The aim of this study was to explore the utility of HPV genotyping and p16INK4a immunostaining (p16) in triaging HPV-positive self-samples, focusing on HPV-positive, cytology-negative (HPCN) women. Methods A total of 73,699 women were screened in a cervical screening project in China via SeqHPV assay on self-samples. HPV-positive women were called-back and collected cervical sample for p16 immunostaining and liquid-based cytology, those who met any result of HPV16/18+ or visual inspection with acetic acid (VIA) + or p16+ were referred for colposcopy, and HPCN women with adequate data on p16 and pathology were analyzed. A triage strategy was considered acceptable if the negative predictive value (NPV) for cervical intraepithelial neoplasia 3 or worse (CIN3+) was 98% or more, combined with an improvement of sensitivity and specificity for CIN2+/CIN3+ in reference to the comparator, being HPV16/18 + . Results A total of 2731 HPCN women aged 30–64 years were enrolled, 136 (5.0%) CIN2+ and 53 (1.9%) CIN3+ were detected. Five triage strategies met the criteria: p16+; HPV16/33+; ‘HPV16+ or HPV33/58/31/35+&p16+’; ‘HPV16/33+ or HPV58/31/35+&p16+’; HPV16/18/31/33/45/52/58 + & p16+. These strategies required less or similar colposcopy referrals, and less colposcopies to detected one case of CIN2+/CIN3+, achieving favorable false positive (negative) rates to the comparator. Among them, p16 staining detected 83.1% (79.2%) of underlying CIN2 + (CIN3+) in HPCN women. Moreover, three triage strategies were favorable in sensitivity and/or specificity to the ‘HPV16/33+’ strategy: p16+; ‘HPV16+ or HPV33/58/31/35 + &p16+’; HPV16/18/31/33/45/52/58 + &p16 + . Conclusions Genotyping for HPV16/33 could be utilized to optimize the management of HPCN women. Moreover, p16 immunostaining, either alone or combined with extended genotypes, is more effective than HPV genotypes alone in the triage of HPCN women.

Self-sampling for human papillomavirus (HPV) testing is an effective option to increase the cervical screening coverage. How to best triage HPV-positive self-samples remains controversial. Here, we evaluated the performance of a novel p16A cohort of 73699 women were screened via SeqHPV assay on self-samples. HPV-positive women who met any sequential positive result of HPV16/18 or VIA or p16 were referred for colposcopy. A triage strategy was considered favorable if the NPV for CIN3+ was ≥98%, combined with an improvement of sensitivity and specificity in comparison to the comparator, being the 'ASC-US+' triage and the guideline strategy (HPV16/18+ or ASC-US+).A total of 3510 HPV-positive women were included, 422 (12.0%) CIN2+ and 247 (7.0%) CIN3+ were identified. The positivity of p16 and ASC-US+ were 36.3% and 22.2%, respectively. p16 was more sensitive and less specific than ASC-US+ (P0.0001). However, when combined p16 with cytology or genotypes, two triage strategies were superior to the 'ASC-US+' strategy: p16 scored 3+; HPV16/33/58/31+p16+. Moreover, four strategies were favorable to the guideline strategy: ASC-US+ or p16+; LSIL+ or p16+; HPV16+ or p16+; HSIL+ or p16+ or HPV16+. These strategies achieved better balance between diseases detection and colposcopy referral.Our findings indicate the promising utility of p16 immunocytology via adjusting the staining score or serving as an ancillary tool to liquid-based cytology or combining with genotyping for the triage of HPV-positive self-samples, which promotes the precise screening of cervical cancer.

Background Self-sampling for human papillomavirus (HPV) testing is a feasible option to improve the cervical screening coverage. However, an ideal triage method for HPV-positive self-samples does not yet exist. The aim of this study was to explore the utility of HPV genotyping and p16INK4a immunostaining (p16) in triaging HPV-positive self-samples, focusing on HPV-positive, cytology-negative (HPCN) women. Methods A total of 73,699 women were screened in a cervical screening project in China via SeqHPV assay on self-samples. HPV-positive women were called-back and collected cervical sample for p16 immunostaining and liquid-based cytology, those who met any result of HPV16/18+ or visual inspection with acetic acid (VIA) + or p16+ were referred for colposcopy, and HPCN women with adequate data on p16 and pathology were analyzed. A triage strategy was considered acceptable if the negative predictive value (NPV) for cervical intraepithelial neoplasia 3 or worse (CIN3+) was 98% or more, combined with an improvement of sensitivity and specificity for CIN2+/CIN3+ in reference to the comparator, being HPV16/18 + . Results A total of 2731 HPCN women aged 30–64 years were enrolled, 136 (5.0%) CIN2+ and 53 (1.9%) CIN3+ were detected. Five triage strategies met the criteria: p16+; HPV16/33+; ‘HPV16+ or HPV33/58/31/35+&p16+’; ‘HPV16/33+ or HPV58/31/35+&p16+’; HPV16/18/31/33/45/52/58 + & p16+. These strategies required less or similar colposcopy referrals, and less colposcopies to detected one case of CIN2+/CIN3+, achieving favorable false positive (negative) rates to the comparator. Among them, p16 staining detected 83.1% (79.2%) of underlying CIN2 + (CIN3+) in HPCN women. Moreover, three triage strategies were favorable in sensitivity and/or specificity to the ‘HPV16/33+’ strategy: p16+; ‘HPV16+ or HPV33/58/31/35 + &p16+’; HPV16/18/31/33/45/52/58 + &p16 + . Conclusions Genotyping for HPV16/33 could be utilized to optimize the management of HPCN women. Moreover, p16 immunostaining, either alone or combined with extended genotypes, is more effective than HPV genotypes alone in the triage of HPCN women. Supplementary Information The online version contains supplementary material available at 10.1186/s12879-021-06109-4.

Additional file 1: Table S1. Positive Predictive Value (PPV) for CIN2+ and CIN3+. Table S2. p16 positivity stratified by HPV genotypes and histologic grades (n, %). Fig. S1. Management protocol of HPV-positive women. VIA, visual inspection under acetic acid; LBC, liquid-based cytology. Genotyping for HPV16/18, VIA, and p16 immunostaining were used for triage sequentially. Fig. S2. p16 immunostaining, (A) positive, one or more cervical epithelial cells with nuclear and/or cytoplasmic stained brownish or yellow were defined as positive regardless of their morphology. (B) negative.

Background: Women with diffuse adenomyosis frequently have severe symptoms, including dysmenorrhea and infertility. Though it is beneficial for long-term health if the uterus can be preserved, there is no prospective investigations to assess lesion removal, symptom alleviation and even gestations after uterus-preservative surgery. Methods: We applied self-optimized PUSH surgery for 146 patients with diffuse adenomyosis and conducted 2 to 11-year follow-up for 114 patients. We detailed procedures in uterine incision , excision of the lesion, uterus reconstruction, solutions for removing giant lesions, and assessed the clinical efficacy and fertility in follow-up. Findings: The average size and volume of the patients’ uterus decreased significantly after PUSH surgery. Operation-related complications occurred in 2.7% (4/146) of the patients. Among 114 patients who had been investigated for ≥2 years, 107 (93.9%, analytic group) had detailed records that was needed to evaluate the long-term outcomes. In analytic group, 5 cases recurred and 95.3% (102/107) of the patients had normal uterine size two years after surgery. The visual analogue scale (VAS) for dysmenorrhea significantly decreased in 102 cases, from 9.35±1.25 to 0.34±0.76 and 0.56±1.06 in the first and second year after surgery, respectively. Additionally, 97.7% of the 86 patients with severe menorrhagia had their symptoms ameliorated in the second year of follow-up. Of the 23 patients who desired for pregnancy and stopped contraception for ≥2 years, 13 (13/23,57%) individuals conceived with17 pregnancies. Twelve patients had 15 intrauterine pregnancies and 7 patients had 8 living fetus. No uterine rupture or severe complications were found in all gestations. Interpretation: This study demonstrate good performance of PUSH surgery in removing uterine lesions, ameliorating menorrhagia and preserving fertility for women with diffuse adenomyosis. Funding: Shenzhen High-level Hospital Construction Fund(YBH2019-260)，Shenzhen Key Medical Discipline Construction Fund(No.SZXK027), Sanming Project of Medicine in Shenzhen(No.SZSM202011016), Scientific Research Foundation of PEKING UNIVERSITY SHENZHEN HOSPITAL(No.KYQD2021075). Declaration of Interest: The authors declare that they have no competing interests. Ethical Approval: The research protocol was approved by the Ethics Committee of Peking University Shenzhen Hospital (IRB approval number: 20190729).

ObjectiveTo assess the prevalence and distribution of HPV genotypes among Chinese Han women, and to explore the risk of high-grade cervical lesions associated with individual hr-HPV genotypes.MethodsGenotyping and histopathology data from the Chinese Multi-Center Screening Trial (CHIMUST) and its pilot screening trial, from 6 regions across mainland China, were re-analyzed. The data from physician (direct) collected samples from 10910 Chinese Han women (ages 30-69) were used to determine the prevalence and distribution of hr-HPV and to explore the risk association between hr-HPV genotypes and precancerous lesions.Results9.1% of the study population tested hr-HPV positive. The prevalence varied regionally rom the lowest in Guangdong (6.3%) to the highest in Inner Mongolia (12.9%). The most prevalent genotypes found were HPV-52 (21.5%), HPV-16 (19.2%), HPV-58 (15.0%), HPV-39 (8.9%), and HPV-51 (8.2%). The overall odds ratios for CIN2+ and CIN3+ for the presence of HPV-16 was 59.7 (95% CI 39.9-89.3) and, 92.0 (95%CI 54.5- 155.3), respectively and remained the highest odds ratio for CIN3+ in all 6 regions.ConclusionGeographical variation exists in the prevalence and distribution of hr-HPV in mainland China. HPV-16/52/58 were the most prevalent genotypes, and HPV-16 had the highest risk for high-grade cervical lesions.

Objective The aim of this research was to evaluate independently the performance of a new isothermal amplification assay for cervical cancer screening compared to two previously validated PCR-based assays and histologic endpoints. Methods This is a sub-study from the Chinese multi-center screening trial (CHIMUST). The self-collected and clinician-collected specimens stored in PreservCyt at − 4 °C from 6042 women with complete data were tested with the AmpFire assay. These specimens had been previously tested with Cobas and SeqHPV assays. In the primary study all patients with an abnormal test were referred to colposcopy where all had directed and/or random biopsies plus ECC. No additional patients were called back based on the AmpFire results. Results 6042/6619 women had complete data (mean age 44.1). There were 57 cases of CIN 2, 35 cases of CIN 3 and 2 cancers. The sensitivity for CIN2+ and CIN3+ were similar among the three assays (both direct and self-collected). For the specificities in all categories (CIN2+/CIN3+ and self and direct collection), isothermal amplification assay was either equal to or more specific than Cobas but consistently less specific than SeqHPV. Conclusion The AmpFire HPV assay showed similar sensitivity to Cobas and SeqHPV for CIN2+ and CIN3+ on both self and clinician-collections (P>0.05), with good specificity. The speed, low cost, and simplicity of this assay will make it particularly suited for low and middle resource settings. Its accuracy with self-collection makes it applicable for mass screening programs.

Objective The performance of Cobas4800 cycle threshold value (Ct-value, reflecting viral load) combined with human papillomavirus (HPV) 16/18 genotyping was explored as a method of risk stratification to triage patients after primary HPV screening of self-collected samples. Methods The Chinese Multi-site Screening Trial database was reviewed, with focus on self-collected samples, using the results of Cobas4800 HPV assay. Quartiles of Ct-values of each genotype were used for grouping and developing screening algorithms. Diagnostic accuracy for paired comparisons between algorithms was obtained using McNemar’s test. Results A total of 10,498 women were included. The Ct-values of HPV16 and other high-risk HPV were inversely correlated with the severity of cervical lesions ( p 0.05), and resulted in a slightly lower specificity than the latter two algorithms (92.6% vs. 97.4% and 95.4% respectively for CIN2+, p Conclusions HPV viral loads reflected by Ct-values are associated with the severity of cervical lesions. Ct-values with an appropriate cut-off of 33.7, combined with HPV16/18 genotyping, represent a promising triage of HPV-positive women particularly for self-collected samples.

Purpose When used for cervical cancer primary screening, liquid-based cytology (LBC) has a high specificity but a low sensitivity. For histological diagnosis of high-grade lesions, p16INK4a immunostaining has proven to be useful. Therefore, our objective was to evaluate the use of p16INK4a immuno-cytology as a primary screen and a secondary screen after primary high-risk human papillomavirus (hrHPV) screening or LBC screening. Methods A total of 1197 cytology slides were immuno-stained using automatic p16INK4a staining system (PathCIN®p16INK4a) in two studies from cervical screening programs. In the primary screening study, 875 slides were randomly selected and analyzed for p16INK4a. In the secondary screening study, 322 of the remaining slides were chosen by virtue of being HPV 16/18+, other hrHPV+/LBC≥ASC-US, or HPV-negative/LBC ≥LSIL. The sensitivity and specificity for detection of cervical intraepithelial neoplasia 2/3 or worse (CIN2+/CIN3+) were compared based on p16INK4a, LBC and HPV test results. Results In combining two studies, there were 431 cases with biopsy pathology. They included 83 cases with CIN2+ and 41 cases with CIN3+. The p16 positivity rate increased with pathologic and cytologic severity (P

The aim of the study was to evaluate the human papillomavirus (HPV) viral load combined with cytology as a secondary screening strategy after primary HPV screening.The data referring to direct Hybrid Capture 2 (HC2), cytology, and histology from Shenzhen Cervical Cancer Screening Trial II were re-analyzed to determine the correlation between viral load and cervical lesions. In addition, algorithms using different viral loads as cut points for immediate colposcopy plus cytology triage were compared with several recommended or controversial primary screening methods.A total of 8,556 women with a mean age of 38.9 years were included in the analysis, of which 13.67% tested high-risk HPV positive with a prevalence of 2.72% for cervical intraepithelial neoplasia 2+ (CIN 2+) and 1.65% for CIN 3+. A significant correlation was observed between increasing relative light units/control (RLU/CO) values and worsening cervical lesions. The mean RLU/CO values for negative, CIN 1, CIN 2, CIN 3, and cancer were 6.86, 119.43, 410.90, 449.39, and 853.26, respectively. A larger proportion of HPV infections with relative high viral load (≥10 RLU/CO) were found in higher-grade lesions. The algorithm using 10 or greater RLU/CO as cut point for immediate colposcopy followed by triage cytology for the other positive (≥110 RLU/CO) had sensitivity of 93.13%/96.45% and specificity of 92.32%/91.44% for CIN 2+/3+, and the colposcopy referral rate was 10.00%.Human papillomavirus viral load level is positively associated with cervical lesion grade. Ten relative light units/control or greater is a viable threshold for immediate colposcopy whereas 1 or greater or less than 10 RLU/CO is advised to reflex cytology for optimizing sensitivity and specificity, as well as referral rates.

Uterine fibroids are common benign tumors in the female reproductive system. A hysterectomy is the most effective treatment for symptomatic fibroids. For patients desiring pregnancy, laparoscopic intracapsular myomectomy (LM) is an alternative surgery option. Although LM is widely accepted to treat fibroids, it is technically demanding with risk of excessive bleeding and difficult suturing, especially in cases with large fibroids or tumors in unusual locations. Therefore, we developed an intracapsular rotary-cut procedure (IRCP) as a modification of laparoscopic intracapsular myomectomy, with the intention to minimize risks of LM and help uterine healing. A summary of the improvements to the IRCP is described: 1) making an incision at the site of the fibroid with a length of one-third to one-half of the fibroid's diameter at a depth reaching the fibroid's surface; 2) holding the fibroid stably and making rotary cuts on the fibroid at a depth of 0.5-1 cm within its pseudo-capsule while pulling it outward slightly, making sure not to cut off any pieces of the fibroid; and 3) repeating the cutting-and-pulling until the longest dimension of the fibroid is outside the incision. The multiple cuts are to minimize the diameter and extend the length of the fibroid. When the multiple cuts cause half of the fibroid body to "shrink", the fibroid is squeezed out by contraction of the surrounding myometrium. Evaluation of the outcomes of IRCP showed that the time of enucleation and suturing, intraoperative bleeding, and decline of hemoglobin were significantly lower in the IRCP group than the LM group. As for reproductive outcomes, the full-term live birth rate of the IRCP group was significantly higher than that of LM group. However, there was no difference in delivery modes between the two groups. In conclusion, IRCP significantly benefits fertility preservation by minimizing damage to the uterus, protecting myofibers of the pseudo-capsule, and resulting in a shallower residual cavity, which eases stitching and causes less bleeding. It is worthwhile to adopt IRCP in younger patients who desire preservation of their fertility.

Background Addressing the burden of HPV-associated diseases among men is increasingly becoming a public health issue. The main objective of this study was to determine HPV prevalence among a healthy community-based Malaysian men. Method This was a cross-sectional study that recruited 503 healthy males from 3 community-based clinics in Selangor, Malaysia. Genital and anal samples were collected from each participant for 14 high risk and 2 low risk HPV DNA detection and genotyping. All participants responded to a set of detailed sociodemographic and sexual behaviour questionnaire. Results The median age at enrolment was 40 years old (IQR: 31–50). The anogenital HPV6/11 prevalence was 3.2% whereas high risk HPV prevalence was 27.1%. The genital HPV prevalence for HPV6/11 was 2.9% while high risk HPV was 18.8%. HPV6/11 prevalence in the anal canal was 1.6% and high risk HPV was 12.7%. HPV 18 was the most prevalent genotype detected in the anogenital area. There was a significant independent association between genital and anal HPV infections. Conclusion Anogenital HPV infection is common among Malaysian men. These findings emphasize the ubiquity of HPV infection and thus the value of population-wide access to HPV prevention.

Background: Community based cervical cancer screening models using self-collection can effectively place the identification of who is positive in the hands of the patient. The key areas we have identified as critical are 1) education, 2) notification of screening opportunities, 3) registration, 4) submission of samples, 5) receiving results with an explanation, and 6) being advised where to receive evaluation and management from qualified healthcare personnel. Methods: Our primary objectives were to create, register, and pilot a website as a public platform for cervical cancer prevention for both city and rural, individual and organizational application. We selected two sites: Shenzhen City in China as the local city (individual participant) site, and Sangzhi County in Hunan Province as the remote (group management) site. The website was reviewable to all of China, but applications for screening and registration were open only to the women from the 2 pilot sites. In the local site, the women would first sign up (obtain a password) to view the website (www.mcareu.com), and then if they desired, they could register for screening using their true name and their state ID. After an offline confirmation of the address, the sampling kit would arrive. Results were available with additional education and guidance for care also on the website. Findings: 120,099 people nationwide visited the website in 27 months by the end of May, 2015, 1148 women from the sites registered at the website and 87.5% enrolled in the pilot trial. 72.3% of those testing positive returned for management. Virtually 100% of the registration/historical information was entered appropriately and 100% of the samples were handled properly. Interpretation: Web-based decision aids help patients through the uncertainties of healthcare. Applied to cervical cancer screening using self-collection, the effectiveness of the model specifically in respect to accessibility, education, registration, data input, and instructions for positive management was clearly demonstrated by this pilot as well as the potential for future diagnostics applicable to self-collection.

ObjectiveTo explore the relationship between the viral load reflected by the Ct value of Cobas 4800 HPV test and cervical lesions, and the effectiveness of the viral load for secondary triage of HPV-positive women.MethodsThe Chinese Multi-Center Screening Trial (CHIMUST) evaluated both self-collected samples and physician-collected samples from women, aged 30 to 59, who were screened for cervical cancer in 6 regions across China. Using physician collected samples, the relationship between the HPV-Ct values of different subtypes and the cervical lesions was analyzed. Then the combined use of the HPV-Ct values with the HPV subtypes was evaluated as a secondary screening algorithm for the women who were HPV positive.ResultsThe Ct values of HPV16 and 12 other HPV subtypes(12-type pool), tested with Cobas decreased with the progression of cervical lesion (HPV16: r = -0.429, P0.05). Compared with HPV16/18 and cytology (HPV16/18 positive and 12-type pool plus cytology ≥ ASC-US), the sequential secondary screening using HPV16/18 and the viral load of 12-type pool (cut-point HPV-Ct≤31) had equal sensitivities for CIN2+ and CIN3+ (83.1%vs.80.3%,100%vs.92.6%,P>0.05), with slightly lower specificities (96.2%vs.94.4%,96.5%vs.93.9%,PConclusionType-specific HPV viral load is closely related to cervical lesions severity. It is feasible and efficient to use HPV16/18 and the viral load of 12 other HPV subtypes (with cut-point HPV-Ct≤31) as the secondary screening for HPV positive women. This algorithm may be useful in low resource regions.

This was a population-based clinical trial of a polymerase chain reaction-based multiplex high-risk human papillomavirus (HR-HPV) assay using mass spectrometry (MassARRAY [Sequenom, San Diego, CA] matrix-assisted laser desorption/ionization time-of-flight mass spectrometry system [MALDI-TOF]). Participants were 10,000 women between the ages of 25 and 59 years in Guangdong Province, China (SHENCCAST II Study). All women collected a self-sample (tested with Cervista [Hologic, Marlborough, MA] and MALDI-TOF) followed by a clinician-collected cervical sample (for cytology, Hybrid Capture 2 [HC2; Qiagen, Gaithersburg, MD], Cervista, and MALDI-TOF). Patients with any abnormal result were asked to return for colposcopy and biopsies. This analysis included the data for 8,556 women. The sensitivity values for cervical intraepithelial neoplasia (CIN) 3 or worse for a direct cervical sample were 97.9%, 95.1%, and 94.3 for HC2, Cervista, and MALDI-TOF, respectively (P > .05). The sensitivity for CIN 3 or worse for a self-collected sample tested with MALDI-TOF was also 94.3%, which was similar to a clinician-obtained endocervical sample assayed with the 3 HR-HPV assays. MALDI-TOF combined with a self-collected sample provides a highly sensitive, high-throughput, low-cost-per-case assay for mass screening.

Our objective was to directly compare the accuracy of the high-risk human papillomavirus (HPV) assays, Hybrid Capture 2 (hc2; Qiagen, Gaithersburg, MD) and Cervista (Hologic, Bedford, MA), in diagnosing cervical intraepithelial neoplasia (CIN) 3 or worse (cancer). A population-based, cross-sectional study (The Shenzhen Cervical Cancer Screening Trial II) was conducted in Guangdong Province in China. Three high-risk HPV assays, self and direct cervical sampling and cytology, were studied. Abnormal results on any of 6 study tests (33%) resulted in referral to colposcopy. At colposcopy, every patient had at least 5 cervical biopsy specimens obtained. For 8,556 women between the ages of 25 and 59 years (mean, 38.9 years), the rate for CIN 3 or worse was 1.6% (141/8,556). The sensitivity (confidence interval) values for CIN 3 or worse were 97.9% (94.0%-99.6%) and 95.1% (90.0%-98.0%) for hc2 and Cervista, respectively (P > .05). The specificity (confidence interval) values were 87.8% (87.1%-88.5%) and 90.3% (89.6%-90.9%), respectively (P < .05). Differences in accuracy in diagnosing CIN 3 or worse with the hc2 and Cervista tests are minor and result from the decisions made in selecting the cut points.

Objectives Determine the ability of the Cobas 4800 assay to detect high-risk human papillomavirus (HrHPV) and high-grade cervical lesions when using cervico-vaginal samples applied to liquid medium and solid media cards compared to a direct cervical sample. Methods Two cervico-vaginal specimens (pseudo self-collected) were obtained from 319 women. One was applied to an iFTA Card (FTA) then the brush placed in liquid-based medium (LSELF); the other was applied to a new solid media: POI card (POI). The clinical performance of Cobas4800 assay using the three aforementioned specimens was compared to direct collected endocervical specimens in liquid media (LDOC). Results The overall agreements of HrHPV detection were 84.2% (LSELF vs. LDOC), 81.0% (FTA vs. LDOC), and 82.3% (POI vs. LDOC). LSELF, FTA and POI identified 98.0%, 79.6%, and 97.5% positive cases of LDOC. Sensitivity to identify CIN2+ were 98.4% (LSELF), 73.8% (FTA), 95.1% (POI), and 93.4% (LDOC) respectively. FTA had 78.1% and 90.4% agreement with the LSELF samples for all HrHPV and HPV16/18 detection respectively, while POI had 91.6% for both. Conclusions Cobas4800 HPV test combined with cervico-vaginal specimens applied to both liquid media and POI solid card are accurate to detect HrHPV infection and high-grade cervical lesions as compared with direct endocervical samples in liquid media.

Background Solid media transport can be used to design adaptable cervical cancer screening programs but currently is limited by one card with published data. Objective To develop and evaluate a solid media transport card for use in high-risk human papillomavirus detection (HR–HPV). Study design The Preventative Oncology International (POI) card was constructed using PK 226 paper ® treated with cell-lysing solution and indicating dye. Vaginal samples were applied to the POI card and the indicating FTA (iFTA) elute card. A cervical sample was placed in liquid media. All specimens were tested for HR–HPV. Color change was assessed at sample application and at card processing. Stability of the POI card and iFTA elute card was tested at humidity. Results 319 women were enrolled. Twelve women had at least one insufficient sample with no difference between media ( p = 0.36). Compared to liquid samples, there was good agreement for HR-HPV detection with kappa of 0.81 (95% CI 0.74–0.88) and 0.71 (95% CI 0.62–0.79) for the POI and iFTA elute card respectively. Sensitivity for ≥CIN2 was 100% (CI 100–100%), 95.1% (CI 92.7–97.6%), and 93.5% (CI 90.7–96.3%) for the HR–HPV test from the liquid media, POI card, and iFTA elute card respectively. There was no color change of the POI card noted in humidity but the iFTA elute card changed color at 90% humidity. Conclusions The POI card is suitable for DNA transport and HR–HPV testing. This card has the potential to make cervical cancer screening programs more affordable worldwide.

Objective To exploit the prevalence of HPV genotypes 52/58 in a Chinese population, we evaluated algorithms that the use the Cervista Assay A9 group for primary cervical cancer screening. Methods The SHENCCAST II trial database was re-analyzed, focussing on the A9 pool of the Cervista HR-HPV Assay. Results for the detection CIN2+ and CIN3+ were correlated with a genotyping assay (MALDI-TOF) and cervical cytology to explore various screening algorithms. Results This analysis included 8,556 women with a mean age of 38.9. CIN 2+ rates were 2.7% (233/8556); CIN 3+ rates were 1.7% (141/8556). Overall HPV infection rates were 11.1% (950/8556) for Cervista, in which A5/A6, A7 and A9 groups were 26.5% (227/950), 22.9% (218/950) and 67.8% (644/950), respectively. The HPV A9 group is highly predictive of high-grade cervical lesions (CIN2+ OR = 103.61, CIN3+ OR = 128.059). Sensitivity and specificity for Cervista A9 group for CIN 2+ was 85.4% and 94.7%, and for CIN 3+ 89.4% and 93.8% respectively. Cervista A9 Assay followed by triage cytology for non-A9 positives has sensitivity and specificity for CIN2+ of 91.5% of 93.5%, and for CIN 3+ 94.3% and 92.6%. Conclusion Using the Cervista A9 as the primary screen instead of the full Cervista assay, the percentage referred to colposcopy would decrease from 11.1% to 8.8% and percentage requiring cytology would decrease from 11.1% to 3.6%. Sensitivity of detecting CIN 2+(91.5%), CIN3+(94.3%) would remain similar to the complete Cervista HR-HPV assay for CIN 2+(93.1%), CIN3+(95.0%).

Objective To develop and implement a community based model for cervical cancer prevention that allows the communities to manage the screening and the healthcare system to focus resources on evaluation and management of the positives. Methods Using self-sampling and the concepts founded in Community Based Participatory Research (CBPR), we progressively developed a model to efficiently reach the women, especially rural communities; and collect the volume of samples needed to support high throughput centralized low cost per case processing. Results 8382 eligible women, ages 35 to 59, in 130 rural communities participated. The screening was organized by the local government administration and conducted by the community leaders (CLs). The model used was progressively designed through detailed assessment of key elements at 6 decision points in 26 workshops that were used to train the CLs and the local promoters. The communities were able to accurately conduct the screening; in the final model a local medical worker conducted a 50-minute workshop featuring instructional posters and structured role-play. A manual and a workshop DVD were created for distribution to and implementation by local governments. The average callback rate was 84.3%, without involvement of the local doctors in the management of the positives. Conclusion An efficient community based model capable of massive screening events was developed. We believe that the callback rate will be further improved when local doctors are trained in the management of the positives. Many elements impact coverage and further research is needed to define the influence of the identified key variables.

Testing for high-risk types of human papillomavirus (HPV) has been consistently more sensitive than cervical cytology for high-grade precancers and cancers of the cervix (cervical intraepithelial neoplasia grade 2 or higher) but less specific. New assays are being developed to improve on the overall accuracy of molecular testing. The Gen-Probe APTIMA HPV assay (AHPV) is a multiplex assay that qualitatively detects 14 HPV types in a single tube. Because the AHPV targets HPV-E6/E7 messenger RNA transcripts, it should theoretically have a greater specificity than HPV assays that detect HPV DNA. The objective of this study was to compare the sensitivity and the specificity of the Gen-Probe AHPV with those of the Qiagen Hybrid Capture 2 assay (HC2) and liquid-based cytologic examination for cervical cancer screening.A total of 2098 unscreened or poorly screened women 25 to 59 years of age were recruited in the city of Shenzhen, China. Two cervical specimens were collected: 1 in SurePath liquid for cytologic examination and 1 in PreservCyt for HPV testing by HC2 and the AHPV. The testing was performed by blinded technicians according to the manufacturer's instructions. Women who had atypical squamous cells of undetermined significance or worse cytologic diagnosis and/or were HPV positive by either assay were asked to return for colposcopy and biopsy.Overall, 2095 women had complete data. Overall, 16.5% of the women were positive on HC2, 10.1% were positive on the AHPV, 5.45% had atypical squamous cells of undetermined significance or greater on cytologic examination, and 1.4% had histologically confirmed cervical disease: cervical intraepithelial neoplasia grade 2 or higher. The sensitivity values of liquid-based cytologic examination, HC2, and the AHPV were 66.7%, 88.9%, and 100%, respectively. The specificity values were 95.5%, 84.5%, and 91.2%, respectively. The AHPV was significantly more accurate by receiver operating characteristic curve comparison (P = 0.005).The low false-positive rate (high specificity) and the high sensitivity of the AHPV makes this assay suitable for use as a primary assay for detecting cervical disease in a screening setting.