High-grade Abnormalities Research Articles

Epigenome-wide differential methylation and differential variability as predictors of high-grade cervical intraepithelial neoplasia (cin2+).

CpG site methylation patterns have potential to improve differentiation of high-grade screening-detected cervical abnormalities. We assessed CpG differential methylation (DM) and differential variability (DV) in high-grade (CIN2+) vs. low-grade (≤CIN1) lesions. In ≤CIN1 (n=117) and CIN2+ (n=31) samples, cervical sample DNA underwent testing with Illumina HumanMethylation arrays. We assessed DM and DV of CpG methylation M values among nine cervical cancer-associated genes. We fit CpG-specific linear models and estimated empirical Bayes standard errors and false discovery rates (FDR). An exploratory epigenome-wide association study (EWAS) aimed to detect novel DM and DV CpGs (FDR<0.05) and Gene Ontology (GO) term enrichment. Compared to ≤CIN1, CIN2+ exhibited greater methylation at CCNA1 Cluster 1 (M value difference 0.24; 95% CI 0.04, 0.43) and RARB Cluster 2 (0.16; 95% CI 0.05, 0.28), and lower methylation at CDH1 Cluster 1 (-0.15; 95% CI -0.26, -0.04). CIN2+ exhibited lower variability at CDH1 Cluster 2 (variation difference -0.24; 95% CI -0.41, -0.05) and FHIT Cluster 1 (-0.30; 95% CI -0.50, -0.09). EWAS detected 3,534 DM and 270 DV CpGs. Forty-four GO terms were enriched with DM CpGs related to transcriptional, structural, developmental, and neuronal processes. Methylation patterns may help triage screening-detected cervical abnormalities and inform US screening algorithms.

Aptima HPV Genotypes in Abnormal Cervical Samples in Different Age Groups - Implication on Vaccination Strategies.

Persistent infection with high-risk human papillomavirus (hr-HPV) types is associated with high-grade cervical abnormalities. The aim of the study was to find most hr-HPV types causing persistent infection in abnormal cytological samples using Aptima HPV testing and discuss the compatibility of the Gardasil 9 vaccine in targeting most types. The study was conducted in a cytology laboratory in a tertiary hospital. This is a retrospective observational study. Cytology and HPV Aptima test reports were obtained for abnormal cervical samples for a 6-year period. Pearson Chi-square test. Reports of 2834 abnormal cervical samples were analyzed. Aptima testing was positive in 21% of samples, including 92% of squamous cell carcinoma (SCC), 76.4% of the high-grade squamous intraepithelial lesion (HSIL), 52% of low-grade squamous intraepithelial lesion (LSIL), 40% of adenocarcinoma (ADC), and 21% of atypical squamous cells that cannot exclude HSIL (ASC-H). The Aptima other hr-HPV group was most common (60%), HPV16 was 26%, HPV18/45 was 9.6%, and double HPV infection was 4.3%. HPV16 was the most common infection in HSIL+ cases. HPV infection was most common in age groups (30-39) and (40-49), and a shift to age groups (50-59) and ≥60 was seen in HSIL+ cases. This study is the first of its kind in correlating age with hr-HPV and cytology findings in the Middle East and adds to previous knowledge related to the prevalence and Aptima testing of HPV. The outcome could be used as a baseline for the Gardasil 9 vaccine and for the assessment of its effectiveness after three or five years from initiation.

EFFICACY OF SEE AND TREAT IN A CERVICAL SCREENING PROGRAM WITH VISUAL INSPECTION WITH ACETIC ACID (VIA)

SEE and TREAT at Colposcopy has been described in cytology based screening when a high-grade lesion in association with a high grade abnormality in the Pap smear is treated by Large Loop Excision of the Transformation Zone (LLETZ) to minimize loss to follow-up in the multiple step management protocol for CIN. With a vast burden of cervical cancerin developing countries, our aim was to study the efficacy of this approach in patients coming to colposcopy clinic after a positive VIA test. Women in the age group of 25-50years and coming to the general gynecology clinichad opportunistic screening with VIA those who were found VIA+ underwent Colposcopy. Ifcolposcopy suggested a high-grade lesion, SEE and TREAT using LLETZ was performed.Colposcopy was carried out for 688VIA positive womenof whom 101 had a high-grade lesion and underwent LLETZ. All of them had CIN on histopathology. Thirty-five (34.6%) had CIN 1, 55 (54.5%) had CIN 2 and 11 (10.9%) has CIN 3. Treatment was described as effective if there was CIN of any grade in the LLETZ specimen overtreatment if there was no CIN. The SEE and TREAT approach was effective in all with no overtreatment. Complete excision was achieved in 96.04%women, 3.96% had positive resection margin.There were no major complications. Thus we conclude that a SEE AND TREAT approach in a low-resource setting with VIA followed by Colposcopy and treatment can help in reducing the number of visits and loss to follow-up.

Cervical cancer prevention by vaccination: review.

Routine use of human papillomavirus (HPV) vaccines is recommended in adolescents under 15 years of age worldwide. Still, effective programs remain suboptimal for several factors, making the WHO strategy to eradicate cervical cancer public health with an uncertain future. To review the literature on the effectiveness, long-term protection, and safety of HPV vaccination programs and vaccination as adjuvant management. This review aims to describe the current state of vaccination programs and demonstrate the long-term protection and safety of vaccines implemented worldwide targeting adolescent girls, with the most recent published evidence of the three prophylactic HPV vaccines - bivalent (bHPV), quadrivalent (qHPV), and nonavalent (nHPV)-. We mainly focus on publications evaluating efficacy, dosing schemes, and HPV vaccination, as well as studies contributing to the mounting evidence for the real-life effectiveness of prophylactic HPV vaccines from several countries. Human Papillomavirus vaccination programs have made remarkable strides in preventing HPV-related diseases; countries with robust vaccination efforts have witnessed substantial reductions in HPV-related diseases with a decline in high-grade cervical abnormalities and genital warts (54%-83%). However, global coverage remains uneven, with disparities between high-income (HICs) and low-income countries (LMICs). The long-term efficacy of the available human papillomavirus (HPV) goes up to 9.4 years and continues to be immunogenic and well tolerated with an excellent safety profile. As these are crucial topics in HPV vaccination, it is essential to establish systems for continued monitoring of vaccine immunogenicity, efficacy, and safety over time.

Aerobic vaginitis is associated with carbonic anhydrase IX in cervical intraepithelial neoplasia

The aim of this study was to analyze the association between vaginal microbiota, carbonic anhydrase IX (CAIX) and histological findings of cervical intraepithelial neoplasia (CIN). The study included 132 females, among them 66 were diagnosed with high-grade intraepithelial lesion (CIN2, CIN3, and cancer), 14 with low-grade disease, and 52 assigned to the control group. An interview focused on the behavior risk factors, together with vaginal fluid pH measurement, wet mount microscopy, detection of Chlamydia trachomatis, and Trichomonas vaginalis were performed. After colposcopy, high-grade abnormalities were detected via direct biopsies and treated with conization procedure. Conuses were immuno-stained with CAIX antibody. The histological findings were CIN1 (n = 14), and CIN2+ (included CIN2 (n = 10), CIN3 (n = 49), and cancer (n = 7; squamous cell carcinomas)). Prevalence of bacterial vaginosis (BV) was similar between the groups. Moderate or severe aerobic vaginitis (msAV) was diagnosed more often among CIN2+ (53.0%) than CIN1 (21.4%). Moderate or strong immunostaining of CAIX (msCAIX) was not detected among CIN1 cases. Thus, msAV was prevalent in CAIX non-stained group (p = 0.049) among CIN2 patients. Co-location of msAV and msCAIX was found in CIN3. Regression model revealed that msAV associated with high-grade cervical intraepithelial neoplasia independently from smoking and the number of partners.

Temporary-Permanent Pacemakers in the Management of Conduction Abnormalities in Patients Undergoing Transcatheter Aortic Valve Replacement

BackgroundInjury to the cardiac conduction system requiring a permanent pacemaker (PPM) implantation is a known adverse outcome of transcatheter aortic valve replacement (TAVR). Temporary-permanent pacemakers (TPPM) have been used as a bridge to PPM implantation in patients with systemic infection; however, there are only a few reports of its routine use in patients undergoing TAVR. This study aimed to assess the utility of routine use of TPPM in patients undergoing TAVR with a high risk of needing a PPM or those who develop high-grade conduction abnormalities during/after TAVR. MethodsBetween April 2015 and December 2021, 978 patients underwent TAVR at our institution, of whom 111 patients had TPPM placed before or during/after TAVR during the study period. In total, 89 patients were included in the final analysis. ResultsThe median age was 78 years (IQR, 71-84 years); 52 (58.4%) patients with preexisting native conduction disease were considered high risk for advanced heart block and had TPPM placed before TAVR. In addition, 37 (41.6%) patients had TPPM placed during/after TAVR. Of the 89 patients who received TPPM, 51 (57.3%) were treated with a balloon-expandable valve and 38 (42.7%) with a self-expandable valve. Of the patients who underwent TPPM placement, only 49 (55.1%) required a PPM, and TPPM was removed in 40 (44.9%) patients. TPPM was in place for a median of 6 days (IQR, 2-11 days). Only 1 of the 89 patients (1.1%) who received a TPPM had lead dislodgment. No other complications were noted. Median length of stay was 3 days (IQR, 2-4 days). ConclusionsIn patients with high-risk baseline conduction abnormalities before TAVR and those who develop new high-grade conduction abnormalities during/after TAVR, TPPM provides a feasible and safe method for pacing that could allow early ambulation, facilitate early discharge, and prevent unnecessary PPM implantations in some patients.

Guideline adherent colposcopy completion following abnormal cervical cancer screening.

e17510 Background: Cervical cancer (CC) prevention relies upon timely management of abnormal screening results. Established recommended follow-up intervals for colposcopy after abnormal CC screening results exist for high-grade and low-grade abnormalities. Despite these guidelines, CC incidence is disproportionately higher in Black and Hispanic/Latino women in the US. Differential follow-up of abnormal screening results and delays in diagnosis may contribute to these disparities despite well-defined CC prevention measures. We investigated factors associated with guideline adherent colposcopy scheduling and attendance. Methods: Clinical and demographic medical record data was collected for patients with abnormal CC screening results from 2/2021 to 1/2022 at a large urban OB/GYN clinic in Connecticut. Timely colposcopy was defined as completion within 8 weeks from final CC screening result for high-grade abnormalities and 90 days for low-grade abnormalities. Clinical and demographic characteristics of patients needing colposcopy were examined. Association between these factors and completion of guideline adherent colposcopy was evaluated using univariate and multivariate regression. Colposcopy scheduling and attendance outcomes were compared by Pap grade using univariate regression and the Mann Whitney U test. Results: Overall, most of the 248 patients needing colposcopy identified as Black or Hispanic, spoke English, were publicly insured, had a low-grade Pap abnormality, and never smoked; half had received at least one dose of HPV vaccine. Among them, 215 (87%) received colposcopy ever and 190 (77%) received colposcopy within the guideline recommend interval. Race/ethnicity, preferred language, insurance status, pap grade, and smoking status were not significantly associated with receipt of timely colposcopy. In multivariate analysis only pregnancy was significantly associated with colposcopy receipt within the guideline recommended interval (RR=1.37, 95% CI: 1.11–1.69, p=0.004). There was no difference in receipt of colposcopy by pap grade. Scheduling of an initial colposcopy appointment was significantly lower among women with low-grade vs. high-grade CC screening abnormalities (94% vs. 100%, RR=1.03, 95% CI: 1.01–1.04, p&lt;0.001). Patients with low-grade vs. high-grade abnormalities experienced similar numbers of no shows or cancellations for colposcopy appointments, with a maximum of 4 no shows or cancellations in each group. Conclusions: Evaluation of abnormal CC screening with colposcopy within guideline adherent time intervals can reduce diagnostic delays. Except for pregnancy, when there is increased interaction with healthcare, no other factors were associated with timely receipt of colposcopy. Further research on factors associated with receipt of colposcopy can contribute to implementation strategies to improve rates of timely follow-up for CC prevention.

Older women testing positive for HPV16/18 on cervical screening and risk of high-grade cervical abnormality.

In Australia's HPV-based cervical screening program, we previously showed that risk of histological high-grade abnormality at 1year post screening decreased with age in women with oncogenic HPV. In this study, we followed 878 HPV16/18 positive women aged 55 years and over for up to 3 years post screening test, to determine the proportion with histological high-grade abnormality (HGA, incorporating high-grade squamous intraepithelial abnormality (HSIL), adenocarcinoma in situ (AIS), squamous cell carcinoma (SCC) and adenocarcinoma) and to correlate risk of HGA with liquid-based cytology result and with prior screening history. HGA was detected in 7.8% at 1year and 10.0% at 3 years, with no significant difference (P=.136), despite the number of women with follow-up information significantly increasing from 82.9% to 91.0% (P < .0001). The proportion of HPV16/18 positive women with HGA at 3 years was highest in those with an HSIL cytology result (79.0%) and lowest in those with negative cytology (6.2%). Women with an adequate screening history had fewer HGA than such women with inadequate prior screening (6.6% vs 16.0%, P=.001) or with a history of an abnormality (6.6% vs 14.4%, P=.001). HPV16/18 infection in women over 55 years may have a different natural history from that in younger women, in whom HGA are more common after HPV16/18 detection. In HPV-based cervical screening programs, management algorithms for screen-detected abnormalities based on risk stratification should include factors such as age, screening history and index cytology result, so that women receive appropriate investigation and follow-up.

Impact of the Mobile Game FightHPV on Cervical Cancer Screening Attendance: Retrospective Cohort Study

The wide availability of mobile phones has made it easy to disseminate health-related information and make it accessible. With gamification, mobile apps can nudge people to make informed health choices, including attending cervical cancer screening. This matched retrospective cohort study examined the association between exposure to the FightHPV mobile app gamified educational content and having a cervical exam in the following year. Women aged 20 to 69 years who signed an electronic consent form after downloading the FightHPV app in 2017 (intervention group) were matched 1:6 with women of the same age and with the same screening history (reference group) in 2015. To estimate the impact of exposure to the FightHPV app, we estimated cumulative incidence and hazard ratios (HRs) with 95% CIs. We used data from the Norwegian Cervical Cancer Screening Program database and Statistics Norway to determine screening participation and outcomes, respectively. We matched 3860 women in the control group to 658 women in the intervention group; 6 months after enrollment, 29.6% (195/658) of the women in the intervention group and 15.21% (587/3860) of those in the reference group underwent a cervical exam (P<.01). Women exposed to the FightHPV app were 2 times more likely to attend screening (adjusted HR 2.3, 95% CI 2.0-2.7), during which they were 13 times more likely to be diagnosed with high-grade abnormality (adjusted HR 12.7, 95% CI 5.0-32.5) than the women in the reference group. Exposure to the FightHPV app significantly increased cervical cancer screening attendance across the various analyses and improved detection of women with high risk for cervical cancer. For the first time, we demonstrated the effectiveness of gamification combined with mobile technology in cancer prevention by empowering women to make active health-related decisions. Gamification can significantly improve the understanding of complicated scientific concepts behind interventions and increase the acceptance of proposed cancer control measures.

The Risk Factors for Cervical Cytological Abnormalities Among Women Infected With Non-16/18 High-Risk Human Papillomavirus: Cross-sectional Study.

High-risk human papillomavirus (hrHPV) infection is a necessary cause of almost all cervical cancers. Relative to hrHPV 16/18 infection, non-16/18 hrHPV infection is of less concern. However, the increasing prevalence of non-16/18 hrHPV infections has become an important public health issue. The early identification and treatment of cervical cytological abnormalities in women infected with non-16/18 hrHPV reduces the incidence of cervical cancer. To date, no study has examined the risk factors for cytological abnormalities in this high-risk population. This population-based, cross-sectional study aimed to identify the risk factors for cervical cytological abnormalities in women infected with non-16/18 hrHPV. A total of 314,587 women from the general population were recruited for cervical cancer screening at 136 primary care hospitals in Xiangyang, China. Of these, 311,604 women underwent HPV genotyping, and 17,523 non-16/18 hrHPV-positive women were referred for cytological screening according to the screening program. A logistic regression model was used to assess the risk factors for cytological abnormalities among these non-16/18 hrHPV-positive women. A separate analysis was performed to determine the factors influencing high-grade cytological abnormalities. The non-16/18 hrHPV infection rate was 5.88% (18,323/311,604), which was 3-fold higher than that of hrHPV 16/18 (6068/311,604, 1.95%). Among the non-16/18 hrHPV-positive women who underwent ThinPrep cytologic test, the overall prevalence rates of cervical cytological abnormalities and high-grade cytological abnormalities were 13.46% (2359/17,523) and 1.18% (206/17,523), respectively. Multivariate logistic regression analysis revealed that women with middle or high school educational attainment were at a higher risk of having cytological abnormalities than those who received primary education (odds ratio [OR] 1.31, 95% CI 1.17-1.45; P<.001, and OR 1.32, 95% CI 1.14-1.53; P<.001, respectively). Living in rural areas (OR 2.58, 95% CI 2.29-2.90; P<.001), gravidity ≥3 (OR 2.77, 95% CI 1.19-6.45; P=.02), cervix abnormalities detected in pelvic examination (OR 1.22, 95% CI 1.11-1.34; P<.001), and having a cervical cancer screening 3 years ago (OR 0.79, 95% CI 0.62-1.00; P=.048) were associated with cytological abnormalities. The risk factors for high-grade cytological abnormalities included middle school education (OR 1.45, 95% CI 1.07-1.98; P=.02), living in rural regions (OR 1.52, 95% CI 1.10-2.10; P=.01), and cervix abnormality (OR 1.72, 95% CI 1.30-2.26; P<.001). The dominant epidemic of non-16/18 hrHPV infection is revealed in Chinese women. Multiple risk factors for cervical cytological abnormalities have been identified in women infected with non-16/18 hrHPV. These findings can provide important information for clinically actionable decisions for the screening, early diagnosis, intervention, and prevention of cervical cancer in non-16/18 hrHPV-positive women.

HPV High-risk Multiple Infection Is a Key Predictor of Cervical Dysplasia in Diagnostic LEEPs: a Retrospective Cohort Analysis.

Objective This study aimed to identify predictors for the presence of cervical dysplasia in diagnostic LEEPs (Loop Electrical Excision Procedure) of the cervix. Materials/Methods The study was designed as a retrospective single-institution cohort analysis of all patients who underwent LEEP without prior proof of high-grade intraepithelial lesion (diagnostic LEEP) between 2015 and 2020 in the Department of Obstetrics and Gynecology of University Hospital Aachen. In order to identify the most meaningful predictive variables for CIN status (CIN2+ or non-CIN2+), multivariate logistic regression was performed and a machine-learning method was used. Results A total of 849 patients with an indication for loop excision of the cervix were assessed for eligibility. Finally, 125 patients without prior proof of CIN2+ were included into the study. Based on the final multivariate logistic regression model, multiple high-risk HPV infections (p=0.001), the presence of a T2 transformation zone (p=0.003) and major lesion changes (p=0.015) as a result of the colposcopy examination were found to be statistically significant for CIN status based on the diagnostic LEEP. Subsequent ROC analysis showed a high predictive value for the model of 88.35% (AUC). The machine-learning technique (recursive partitioning) identified similar variables as important for CIN status with an accuracy of 75%. Conclusion For clinical decision-making, the result of the colposcopy examination (T2, major change) as well as the results of HPV testing (multiple high-risk HPV infections) are stronger indicators for clinicians to perform diagnostic excisional procedures of the cervix than the presence of high-grade cytological abnormalities.

Long-term human papillomavirus vaccination effectiveness and immunity in Rwandan women living with and without HIV: a study protocol

IntroductionProphylactic human papillomavirus (HPV) vaccines have been shown to be highly effective in protecting women against cervical infections, high-grade abnormalities and cancer caused by the targeted HPV types. However, the...

Effectiveness of human papillomavirus vaccine against cervical precancer in Japan: Multivariate analyses adjusted for sexual activity.

Japanese girls aged 12–16 years are offered free human papillomavirus (HPV) vaccination and cervical cancer screening is conducted with cytology and not HPV testing from the age of 20 years. So far, no study has analyzed the effect of HPV vaccination against cervical precancers considering HPV infection status and sexual activity. We aimed to analyze the vaccine effectiveness (VE) against HPV infection and cytological abnormalities, adjusted for sexual activity. This study comprised women aged 20–26 years who underwent cervical screening in Niigata. We obtained HPV vaccination status from municipal records and a questionnaire along with information concerning sexual activity. Of 5194 women registered for this study, final analyses included 3167 women in the vaccinated group (2821 vaccinated women prior to sexual debut) and 1386 women in the unvaccinated group. HPV 16/18 (0.2% vs 3.5%), 31/45/52 (3.4% vs 6.6%), and 31/33/45/52/58 (5.0% vs 9.3%) positive rates were significantly lower in the vaccinated group (P < 0.001). No women vaccinated before sexual debut had HPV 16/18‐related cytological abnormalities. VE for HPV 16/18 infection and high‐grade cytological abnormalities in women vaccinated prior to sexual debut were 95.8% (95% CI 81.9–99.0%; P < 0.001) and 78.3% (95% CI 11.3–94.7%; P = 0.033), respectively, in multivariate analyses adjusted for age and number of sexual partners. However, analyses of all vaccinated women did not show significant effectiveness against cytological abnormalities. Our results showed the effectiveness of HPV vaccine against high‐grade cervical cytological abnormalities and the importance of the vaccination before sexual debut.

A comparison of high-grade cervical abnormality risks in women living with and without human immunodeficiency virus undergoing routine cervical-cancer screening

As the US moves increasingly towards using human papillomavirus (HPV) testing with or without concurrent cytology for cervical cancer screening, it is unknown what the corresponding risks are following a screening result for women living with HIV (WLWH), which will dictate the optimal clinical follow-up. Therefore, using medical records data from Kaiser Permanente Northern California, which introduced triennial HPV and cytology co-testing in women aged 30–64 years in 2003, we compared risks of cervical intraepithelial neoplasia grade 2 (CIN2) or more severe diagnoses (CIN2+) in women not known to have HIV (HIV[−] women) (n = 67,488) frequency matched 111:1 on age and year of the first co-test to the 608 WLWH (n = 608). WLWH were more likely to test HPV positive (20.2% vs. 6.5%, p < 0.001) and have non-normal cytology (14.1% vs. 4.1%, p < 0.001) than HIV[−] women. Five-year CIN2+ risks for all WLWH and HIV[−] women were 3.5% (95%CI = 2.0–5.0%) and 1.6% (95%CI = 1.5–1.8%) (p = 0.01), respectively. Five-year CIN2+ risks for WLWH with positive HPV and non-normal cytology, positive HPV and normal cytology, negative HPV and non-normal cytology, and negative HPV and normal cytology were 24.9% (95%CI = 13.4–36.4%), 3.0% (95%CI = 0.0–7.4%), 3.6 (95%CI = 0.0–9.8%) and 0.3% (95%CI = 0.0–0.8%), respectively. Corresponding 5-year CIN2+ risks for HIV[−] women were 26.6% (95%CI = 24.6–28.7%), 8.5% (95%CI = 7.2–9.9%), 1.9% (95%CI = 1.0–2.8%), and 0.5% (95%CI = 0.4–0.6%), respectively. Thus, in this healthcare setting, the main cause in overall CIN2+ risk differences between WLWH and HIV[−] women was the former was more likely to screen positive and once the screening result is known, it may be reasonable to manage both populations similarly.

Different human papillomavirus types share early natural history transitions in immunocompetent women.

Necessary stages of cervical carcinogenesis include acquisition of a carcinogenic human papillomavirus (HPV) type, persistence associated with the development of precancerous lesions, and invasion. Using prospective data from immunocompetent women in the Guanacaste HPV Natural History Study (NHS), the ASCUS-LSIL Triage Study (ALTS) and the Costa Rica HPV Vaccine Trial (CVT), we compared the early natural history of HPV types to inform transition probabilities for health decision models. We excluded women with evidence of high-grade cervical abnormalities at any point during follow-up and restricted the analysis to incident infections in all women and prevalent infections in young women (aged <30 years). We used survival approaches accounting for interval-censoring to estimate the time to clearance distribution for 20 529 HPV infections (64% were incident and 51% were carcinogenic). Time to clearance was similar across HPV types and risk classes (HPV16, HPV18/45, HPV31/33/35/52/58, HPV 39/51/56/59 and noncarcinogenic HPV types); and by age group (18-29, 30-44 and 45-54 years), among carcinogenic and noncarcinogenic infections. Similar time to clearance across HPV types suggests that relative prevalence can predict relative incidence. We confirmed that there was a uniform linear association between incident and prevalent infections for all HPV types within each study cohort. In the absence of progression to precancer, we observed similar time to clearance for incident infections across HPV types and risk classes. A singular clearance function for incident HPV infections has important implications for the refinement of microsimulation models used to evaluate the cost-effectiveness of novel prevention technologies.

The impact of catch-up bivalent human papillomavirus vaccination on cervical screening outcomes: an observational study from the English HPV primary screening pilot

BackgroundIn England, bivalent vaccination (Cervarix) against high-risk human papillomavirus (HR-HPV) genotypes 16/18 was offered in a population-based catch-up campaign in 2008–2010 to girls aged 14–17 years. These women are now entering the national cervical screening programme. We determined the impact of catch-up bivalent vaccination on their screening outcomes.MethodsWe studied the overall and genotype-specific screening outcomes in 108,138 women aged 24–25 (offered vaccination) and 26–29 years (not offered vaccination) included in the English HPV screening pilot between 2013 and 2018.ResultsAt 24–25 years, the detection of high-grade cervical intraepithelial neoplasia (CIN2+) associated with HPV16/18 decreased from 3 to 1% (p < 0.001), with estimated vaccine effectiveness of 87% (95% CI: 82–91%). The detection of any CIN2+ halved from 6 to 3% (p < 0.001), with an estimated vaccine effectiveness of 72% (95% CI: 66–77%). The positive predictive value of a colposcopy for CIN2+ decreased for both low-grade (p < 0.001) and high-grade (p = 0.02) abnormalities on triage cytology. The decreases in screen-detected abnormalities at age 26-29 were of a substantially smaller magnitude.ConclusionsThese data confirm high effectiveness of bivalent HPV vaccination delivered through a population-based catch-up campaign in England. These findings add to the rationale for extending screening intervals for vaccinated cohorts.

Vaginal vault smear cytology in detection of recurrence after hysterectomy for early cervical cancer

ObjectiveTo determine the role of vaginal vault cytology as a surveillance tool for the detection of recurrence in patients with early stage cervical cancer treated with hysterectomy without adjuvant therapy.MethodsA...

Selinexor in Combination with Carboplatin and Pemetrexed in Patients with Advanced or Metastatic Solid Tumors: Results of an Open-Label, Single-Center, Multi-Arm Phase 1b Study.

Selinexor in Combination with Carboplatin and Pemetrexed in Patients with Advanced or Metastatic Solid Tumors: Results of an Open-Label, Single-Center, Multi-Arm Phase 1b Study.

Deep multiple-instance learning for abnormal cell detection in cervical histopathology images

Cervical cancer is a disease of significant concern affecting women's health worldwide. Early detection of and treatment at the precancerous stage can help reduce mortality. High-grade cervical abnormalities and precancer are confirmed using microscopic analysis of cervical histopathology. However, manual analysis of cervical biopsy slides is time-consuming, needs expert pathologists, and suffers from reader variability errors. Prior work in the literature has suggested using automated image analysis algorithms for analyzing cervical histopathology images captured with the whole slide digital scanners (e.g., Aperio, Hamamatsu, etc.). However, whole-slide digital tissue scanners with good optical magnification and acceptable imaging quality are cost-prohibitive and difficult to acquire in low and middle-resource regions. Hence, the development of low-cost imaging systems and automated image analysis algorithms are of critical importance. Motivated by this, we conduct an experimental study to assess the feasibility of developing a low-cost diagnostic system with the H&E stained cervical tissue image analysis algorithm. In our imaging system, the image acquisition is performed by a smartphone affixing it on the top of a commonly available light microscope which magnifies the cervical tissues. The images are not captured in a constant optical magnification, and, unlike whole-slide scanners, our imaging system is unable to record the magnification. The images are mega-pixel images and are labeled based on the presence of abnormal cells. In our dataset, there are total 1331 (train: 846, validation: 116 test: 369) images. We formulate the classification task as a deep multiple instance learning problem and quantitatively evaluate the classification performance of four different types of multiple instance learning algorithms trained with five different architectures designed with varying instance sizes. Finally, we designed a sparse attention-based multiple instance learning framework that can produce a maximum of 84.55% classification accuracy on the test set.

Follow-up after abnormal cervical cancer screening in immigrants compared with Danish-born women – A nationwide register study

Cervical cancer screening is offered free-of-charge to women aged 23–64 years in Denmark. Immigrants participate less in screening than Danish-born women, but little is known about their participation in follow-up after abnormal screening results. In this registry-based cohort study, we examined the likelihood of timely follow-up after an abnormal cervical cytology in immigrants from different countries and regions compared with Danish-born women. In nationwide registers, we identified women aged 23–64 years with high-grade (n = 74,335) or low-grade (n = 174,038) abnormal cytology during 1997–2017. Timely follow-up was defined as a new examination within six months for high-grade and 18 months for low-grade abnormalities. We calculated the probability of timely follow-up by country and region of origin and estimated odds ratios (ORs) of timely follow-up between immigrants and Danish-born women. The proportions with timely follow-up after high-grade abnormalities ranged from 90.6%–95.1% in immigrants from different countries or regions, compared with 95.5% in Danish-born women. For low-grade abnormalities, follow-up ranged from 75.2%–92.8% in immigrants, compared with 90.6% in Danish-born women. Women from Sub-Saharan Africa had low probability of timely follow-up after both high-grade (90.9%) and low-grade (75.2%) abnormalities. The differences between immigrants and Danish-born women remained when adjusting for age, year, income, employment and marital status. In conclusion, immigrants from most countries and regions were slightly less likely than Danish-born women to receive timely follow-up after abnormal cervical cytology, also after adjusting for socioeconomic differences. Efforts should be made to improve follow-up of abnormal screening results in immigrant groups with low attendance.