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Background US population-based cancer registries can be used for surveillance of human papillomavirus (HPV) types found in HPV-associated cancers. Using this framework, HPV prevalence among high-grade cervical precancers and invasive cervical cancers were compared before and after HPV vaccine availability. Methods Archived tissue from 2 studies of cervical precancers and invasive cervical cancers diagnosed from 1993-2005 (prevaccine) were identified from 7 central cancer registries in Florida; Hawaii; Iowa; Kentucky; Louisiana; Los Angeles County, California; and Michigan; from 2014 through 2015 (postvaccine) cases were identified from 3 registries in Iowa, Kentucky, and Louisiana. HPV testing was performed using L1 consensus polymerase chain reaction analysis. HPV-type-specific prevalence was examined grouped by hierarchical attribution to vaccine types: HPV 16, 18, HPV 31, 33, 45, 52, 58, other oncogenic HPV types, and other types/HPV negative. Generalized logit models were used to compare HPV prevalence in the prevaccine study to the postvaccine study by patient age, adjusting for sampling factors. Results A total of 676 precancers (328 prevaccine and 348 postvaccine) and 1140 invasive cervical cancers (777 prevaccine and 363 postvaccine) were typed. No differences were observed in HPV-type prevalence by patient age between the 2 studies among precancers or invasive cancers. Conclusions The lack of reduction in vaccine-type prevalence between the 2 studies is likely explained by the low number of cases and low HPV vaccination coverage among women in the postvaccine study. Monitoring HPV-type prevalence through population-based strategies will continue to be important in evaluating the impact of the HPV vaccine.

OBJECTIVE The aim of the study was to describe trends in human papillomavirus (HPV) testing preceding diagnosis of cervical precancer during a time of changing screening recommendations. MATERIALS AND METHODS We conducted a cross-sectional analysis of data from active, population-based, laboratory surveillance among 1.5 million residents of 5 areas in the United States. We included women aged 21-39 years diagnosed with cervical intraepithelial neoplasia grades 2, 2/3, or 3 or adenocarcinoma in situ (collectively, CIN2+) during 2008-2016, who had a cytology and/or HPV test before diagnosis (n = 16,359). RESULTS The proportion of women with an HPV test preceding CIN2+ increased from 42.9% in 2008 to 73.3% in 2016 (p < .01); testing increased in all age groups (21-24 y: 35.3% to 47.6%, 25-29 y: 40.9% to 64.1%, 30-39 y: 51.7% to 85.9%, all p < .01). The HPV testing varied by cytology result and was highest among women with atypical squamous cells of unknown significance (n = 4,310/4,629, 93.1%), negative for intraepithelial lesion or malignancy (n = 446/517, 86.3%), and atypical glandular cells (n = 145/257, 56.4%). By 2016, at least half of all cases in every surveillance area had an HPV test before diagnosis. CONCLUSIONS During 2008-2016, the proportion of women with an HPV test preceding CIN2+ increased significantly for all age groups, cytology results, and surveillance areas. By 2016, most (85.9%) women aged 30-39 years had an HPV test, consistent with recommendations. Increasing utilization of HPV tests, which have demonstrated improved sensitivity for detecting cervical disease, may in part explain increasing rates of cervical precancer among women 30 years and older.

Xiao Huo,1,* Hengzi Sun,2,3,* Dongyan Cao,3 Jiaxin Yang,3 Peng Peng,3 Linghua Kong,3 Fei Chen,3 Keng Shen,3 Shuhong Li2 1Center of Basic Medical Research, Peking University Third Hospital Institute of Medical Innovation and Research, Beijing, People’s Republic of China; 2Department of Obstetrics and Gynecology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People’s Republic of China; 3Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shuhong LiDepartment of Obstetrics and Gynecology, Beijing Chao-Yang Hospital, Capital Medical University, No. 8 GongTiNan Road, Beijing, People’s Republic of ChinaTel +86-10-8523 1831Email 1544563468@qq.comKeng ShenDepartment of Obstetrics and Gynecology, Peking Union Medical College Hospital, No. 1 Shuaifuyuan, Dongcheng District, Beijing, 100730, People’s Republic of ChinaEmail shenkengpumc@163.comBackground: Colposcopy was referred in cases with severe abnormalities in co-testing. Although p16/Ki67 dual staining reduced the referral rate, its sensitivity and specificity need to be enhanced.Methods: The expressions of p16, Ki-67, SMAD3, YAP1, RELA were evaluated in the colposcopy referral population. The inclusion criteria included 30– 60 years and diagnosed with HPV16/18-positive, other HR-HPV-positive with ASCUS, LSIL, AGC (atypical glandular cell) in co-testing. Colposcopies, endocervical curettages of cervical biopsies were also collected. Cases were excluded if there were no biopsies, if the interval between a cervical screening test and biopsies was more than 6 months, or if insufficient tissue was available as a formalin-fixed paraffin-embedded block. The pathology was independently reviewed by two pathologists. Discrepant interpretations were adjudicated by a third pathologist.Results: In total, 1194 of 1273 cases who were referred to colposcopy were evaluated in the present study. The sensitivity and specificity of p16+ combined with Ki-67+ for predicting CIN2+ were 62.1% and 89.5%, respectively. p16+ combined with YAP1+ and/or RELA+ provided a sensitivity and specificity of 70.9% and 89.5%, respectively, while 72.8% and 86.4% were achieved by p16+ combined with YAP1+ and/or SMAD3+ and/or RELA+. In HPV16/18+ and LSIL subgroups, the sensitivity and specificity of p16+ combined with Ki-67+ for predicting CIN2+ were 67.7% and 87.6%, respectively, for the former group and 58.6%, 88.8%, respectively, for the latter group. p16+, YAP1+/RELA+ showed a better performance for predicting CIN2+ with a better sensitivity and considerable specificity in the other HPV+ combined with ASCUS group than were achieved by p16+ combined with Ki-67+. RELA+ and the combination of p16 and RELA/YAP1 also provided the Max AUC area.Conclusion: Our study shows that RELA and the combination of p16 and RELA/YAP1 achieved better sensitivity and specificity for detecting morphologically CIN2+ lesions.Keywords: cervical precancer, immunocytochemical strategy, morphological marker, colposcopy triage

Background: Data are lacking regarding which human papillomavirus (HPV) types cause high-grade cervical neoplasia (CIN2+) in people with HIV in Europe. We assessed which HPV types are associated with CIN2+ in women living in Sweden by HIV status. Methods: The Swedish National HIV Registry, the Swedish Population Registry, and the Swedish National Cervical Screening Registry were linked. CIN2+ tissue blocks of 130 women living with HIV (WLWH) and 234 HIV-negative women, matched for country of birth (1:2), were retrieved from bio-banks and HPV genotyped. Adjusted ORs (adjOR), stratified by country of birth, were calculated using conditional logistic regression. Matching was broken for cross-group comparisons. Results: WLWH with CIN2 were less likely to have HPV16 [14% vs. 40%; adjOR 0.1; 95% confidence interval (CI), 0.04–0.56] than HIV-negative women, but among women with CIN3, there was no difference in HPV16 prevalence by HIV status (adjOR 0.9; 95% CI, 0.51–1.70). WLWH were six times more likely to have HPV35 in CIN3 than HIV-negative women (adjOR 6.2; 95% CI, 1.3–30.4). WLWH from sub-Saharan Africa (SSA) had less 9-valent vaccine types, compared with both HIV-negative women born in Sweden (adjOR 0.1; 95% CI, 0.02–0.44) and WLWH born in Sweden (adjOR 0.1; 95% CI, 0.01–0.73), mostly because of decreased HPV16 and increased HPV35. Conclusions: WLWH from SSA were less likely to be covered by the 9-valent vaccine, mostly due to less HPV16 and more HPV35. Impact: This could have implications for HPV vaccines, currently not including HPV35, and for HPV-screening algorithms in women with origin from SSA.

PURPOSE This study aims to assess the detection of cervical intraepithelial lesions grades 2 and 3 (CIN2-3) at 1 year after treatment with thermal ablation among human papillomavirus (HPV)–positive and visual inspection with acetic acid (VIA)–positive women. METHODS All women screened and triaged for cervical cancer at four government health facilities in Honduras who were eligible for ablative treatment were enrolled and treated with thermal ablation. Women with confirmed CIN2-3 and a subset of women with CIN1/normal diagnoses at baseline were evaluated at 12 months. Follow-up procedures included HPV testing ( careHPV), VIA, directed biopsy (if VIA-positive), and Papanicolaou test (if HPV positive, VIA negative). Outcomes at 1 year included histologic or cytologic assessment of CIN lesions among those with any abnormal test. RESULTS Among the 319 women treated with thermal ablation, baseline histologic diagnoses were available for 317. Two (0.6%) had invasive cancer, 36 (11.4%) had CIN3, 40 (12.6%) had CIN2, and 239 (75.4%) had CIN1/normal histology. Among the 127 women eligible for follow-up, 118 (92.9%) completed all study procedures at 1 year. Overall, 98 (83.1%) had no evidence of CIN2-3 or persistent low-grade infection, 13 (11.2%) had CIN1/atypical squamous cells of undetermined significance, six (5.1%) had CIN2/high-grade squamous intraepithelial lesion, and 1 (0.8%) had a persistent CIN3. No adverse events associated with thermal ablation at 1 year were registered. CONCLUSION A high proportion of women had no evidence of CIN2-3 at 1 year after thermal ablation treatment. Thermal ablation is an alternative to cryotherapy that may facilitate greater treatment coverage and prevent unnecessary deaths from cervical cancer.

Cervical precancer lesion can generally be seen in the transformation zone. Colposcopy allows us to see an image of enlarge precancer lesion in the transformation zone. The colpocopist should consider some important things to determine the appearance of low-grade lesion or high-grade lesion. Two important things are the description of abnormal epithelium and the description of abnormal blood vessels. The description of the abnormal epithelial seen after administration of acetic acid 3-5%, acetowhite looks faster and disappears slower. The “white” lesion is more concentrated like the color of shells, with clear border and surface contour. To find the abnormal blood vessels more clearly, we can use the green filter. High-grade lesion shows rough mosaic and rough punctation or both. In addition, finding the cervical blood vessels can help us to determine high-grade lesion. By understanding the description of the epithelial cervix and abnormal blood vessels , we will easily distinguish high-grade lesions from low grade lesion. Keywords: cervical precancer, colposcopy findings

Birth cohorts vaccinated against human papillomavirus (HPV) are now entering cervical cancer screening. Assessment of (pre)cancer (CIN3+) risk is needed to assess the residual screening need in vaccinated women. We estimated the lifetime (screen‐detected) CIN3+ risk under five‐yearly primary HPV screening between age 30 and 60, using HPV genotyping and histology data of 21,287 women participating in a screening trial with two HPV‐based screening rounds, 5 years apart. The maximum follow‐up after an HPV‐positive test was 9 years. We re‐estimated the CIN3+ risk after projecting direct vaccine efficacy for the bivalent and the nonavalent HPV vaccines, assuming life‐long protection. The lifetime CIN3+ risk was 4.1% (95% confidence interval 3.5‐4.9) and declined by 53.5% and 70.5% after bivalent vaccination without and with cross‐protection, respectively, translating into a residual lifetime CIN3+ risk of 1.9% (1.4‐2.4) and 1.2% (0.9‐1.5). The CIN3+ risk declined by 88.5% after nonavalent vaccination, translating into a residual lifetime CIN3+ risk of 0.5% (0.2‐0.7). The latter risk increased to 1.6% when vaccine protection only lasted until the first screening round at age 30. Among HPV‐positive women with abnormal adjunct cytology, the nine‐year CIN3+ risk was 16.9% (8.7‐32.4) after nonavalent vaccination. In conclusion, HPV vaccination will lead to a strong decline in the lifetime CIN3+ risk and the remaining absolute CIN3+ risk will be very low. Primary HPV testing combined with adjunct cytology at five‐year intervals still seems feasible even after nonavalent vaccination, although unlikely to be cost‐effective. Our results support a de‐intensification of screening programs in settings with high vaccination coverage., What's new? Human papillomavirus (HPV)‐based screening and vaccination are key strategies for early detection and prevention of cervical intraepithelial neoplasia grade 3 and cancer (CIN3+). Here the authors estimated the lifetime screen‐detected CIN3+ risk expected under different HPV vaccination scenarios using a novel statistical, data‐driven approach that deals with multiple‐type HPV infections. The model estimated that the lifetime CIN3+ risks under five‐yearly primary HPV screening will become very low in vaccinated women, in particular when protection is life‐long and provided beyond genotypes 16 and 18. These CIN3+ risks are important when defining new extended screening intervals for vaccinated cohorts.

The Roche Cobas (Cobas) and BD Onclarity (Onclarity) human papillomavirus (HPV) assays are convenient, PCR-based, HPV DNA tests; currently, data on performance of Onclarity in Chinese women is limited. We aimed to evaluate the clinical performance of Onclarity for detecting cervical lesions in Chinese women.In total, 1122 women were enrolled into this study. Exfoliated cervical cells were collected in PreservCyt medium and were tested using Cobas and Onclarity. Cytology and histology were interpreted by senior cytologists and a panel of pathologists, respectively, at Cancer Hospital, Chinese Academy of Medical Sciences.The assays showed excellent concordance for HPV16 (kappa = 0.91, 95% CI: 0.85-0.97) and for 12 other high-risk types (HPV31/33/35/39/45/51/52/56/58/59/66/68, kappa = 0.84, 95% CI: 0.78-0.90), and very good concordance for HPV18 (kappa = 0.75, 95% CI: 0.69-0.81). No difference for ≥CIN2 sensitivity was observed between Onclarity and Cobas (both 90.5%); and theCIN2 specificity for detection was similar between Onclarity (84.2%, 95% CI: 81.6-86.4) and Cobas (80.4%, 95% CI: 77.6-82.8). When combined with cytology triage, the colposcopy referral rate point estimate was slightly lower for Onclarity (9.0%) than for Cobas (11.0%), with the same ≥CIN2 sensitivity of 75.0% (95% CI: 53.1-88.8) for Onclarity and Cobas.Onclarity exhibited comparable screening performance and triage efficiency compared to Cobas in detection of cervical lesions in Chinese women.

Supplemental digital content is available in the text., Objective To manage cervical screening abnormalities, the 2019 ASCCP management consensus guidelines will recommend clinical action on the basis of risk of cervical precancer and cancer. This article details the methods used to estimate risk, to determine the risk-based management, and to validate that the risk-based recommendations are of general use in different settings. Methods Based on 1.5 million patients undergoing triennial cervical screening by cotesting at the Kaiser Permanente Northern California from 2003 to 2017, we estimated risk profiles for different clinical scenarios and combinations of past and current human papillomavirus and cytology test results. We validated the recommended management by comparing with the estimated risks in several external data sources. Results Risk and management tables are presented separately by Egemen et al.1 and Demarco et al.2 Risk-based management derived from the Kaiser Permanente Northern California largely agreed with the management implied from the estimated risks of the other data sources. Conclusions The new risk-based guidelines present management of abnormal cervical screening results. By describing the steps used to develop these guidelines, the methods presented in this article can provide a basis for future extensions of the risk-based guidelines.

Objective: There are no currently approved options for medical management of cervical intraepithelial neoplasia (CIN) 2/3. This article describes the use of intravaginal 5% 5-fluorouracil (5-FU) fo...

Objective Cervical cancer rates in the United States have declined since the 1940's, however, cervical cancer incidence remains elevated in medically-underserved areas, especially in the Rio Grande Valley (RGV) along the Texas-Mexico border. High-resolution microendoscopy (HRME) is a low-cost, in vivo imaging technique that can identify high-grade precancerous cervical lesions (CIN2+) at the point-of-care. The goal of this study was to evaluate the performance of HRME in medically-underserved areas in Texas, comparing results to a tertiary academic medical center. Methods HRME was evaluated in five different outpatient clinical settings, two in Houston and three in the RGV, with medical providers of varying skill and training. Colposcopy, followed by HRME imaging, was performed on eligible women. The sensitivity and specificity of traditional colposcopy and colposcopy followed by HRME to detect CIN2+ were compared and HRME image quality was evaluated. Results 174 women (227 cervical sites) were included in the final analysis, with 12% (11% of cervical sites) diagnosed with CIN2+ on histopathology. On a per-site basis, a colposcopic impression of low-grade precancer or greater had a sensitivity of 84% and a specificity of 45% to detect CIN2+. While there was no significant difference in sensitivity (76%, p = 0.62), the specificity when using HRME was significantly higher than that of traditional colposcopy (56%, p = 0.01). There was no significant difference in HRME image quality between clinical sites (p = 0.77) or medical providers (p = 0.33). Conclusions HRME imaging increased the specificity for detecting CIN2+ when compared to traditional colposcopy. HRME image quality remained consistent across different clinical settings.

US guidelines recommend that most women older than 65 years cease cervical screening after two consecutive negative cotests (concurrent HPV and cytology tests) in the previous 10 years, with one in the last 5 years. However, this recommendation was based on expert opinion and modeling rather than empirical data on cancer risk. We therefore estimated the 5‐year risks of cervical precancer (cervical intraepithelial neoplasia grade 3 or adenocarcinoma in situ [CIN3]) after one, two and three negative cotests among 346,760 women aged 55–64 years undergoing routine cotesting at Kaiser Permanente Northern California (2003–2015). Women with a history of excisional treatment or CIN2+ were excluded. No woman with one or more negative cotests was diagnosed with cancer during follow‐up. Five‐year risks of CIN3 after one, two, and three consecutive negative cotests were 0.034% (95% CI: 0.023%–0.046%), 0.041% (95% CI: 0.007%–0.076%) and 0.016% (95% CI: 0.000%–0.052%), respectively (p trend < 0.001). These risks did not appreciably differ by a positive cotest result prior to the one, two or three negative cotest(s). Since CIN3 risks after one or more negative cotests were significantly below a proposed 0.12% CIN3+ risk threshold for a 5‐year screening interval, a longer screening interval in these women is justified. However, the choice of how many negative cotests provide sufficient safety against invasive cancer over a woman's remaining life represents a value judgment based on the harms versus benefits of continued screening. Ideally, this guideline should be informed by longer‐term follow‐up given that exiting is a long‐term decision., What's new? US guidelines recommend that women older than 65 years cease screening for cervical cancer following two consecutive negative cotests (HPV and cytology) in the previous ten years. However, these guidelines are based on modelling and expert opinion, rather than empirical data. In this large epidemiological study, the authors estimated the risks of cervical precancer following one, two, or three negative cotests among women aged 55‐64 years. They caution that the optimal time for women to exit screening represents a value judgment, based on the harms versus benefits of continued screening. Further data are needed.

Cervical cancer (CC) is the fourth most common cancer in women worldwide. There is a large body of evidence which shows that smoking interferes with incidence and prevalence of HPV infection and is associated with cervical intraepithelial neoplasia (CIN) and invasive CC. Smoking is a modifiable risk factor; however, there is a lack of studies on targeted cessation strategies and their effectiveness. As HPV vaccination and screening efforts to decrease the incidence of cervical cancer expand worldwide, measures to raise awareness of the link between smoking and cervical cancer have a huge potential to reduce this risk further. This is all the more important in richer countries to drive smoking and cervical cancer rates down.

Cervical cancer remains a major public health concern in developing countries due to financial and human resource constraints. Visual inspection with acetic acid (VIA) of the cervix was widely promoted and routinely used as a low-cost primary screening test in low- and middle-income countries. It can be performed by a variety of health workers and the result is immediate. VIA provides a transient whitening effect which appears and disappears differently in precancerous and cancerous lesions, as compared to benign conditions. Colposcopes are often used during VIA to magnify the view of the cervix and allow clinicians to visually assess it. However, this assessment is generally subjective and unreliable even for experienced clinicians. Computer-aided techniques may improve the accuracy of VIA diagnosis and be an important determinant in the promotion of cervical cancer screening. This work proposes a smartphone-based solution that automatically detects cervical precancer from the dynamic features extracted from videos taken during VIA. The proposed solution achieves a sensitivity and specificity of 0.9 and 0.87 respectively, and could be a solution for screening in countries that suffer from the lack of expensive tools such as colposcopes and well-trained clinicians.

Introduction:cervical precancer screening with same day treatment facilitates maximization of benefits of secondary prevention of cervical cancer. This is particularly important for women living with human immunodeficiency virus (WLHIV) infection because of their exceptional risk for cervical cancer. The availability of HIV programmes in low- and middle-income countries (LMICs) provide unique opportunity for possible introduction “human papillomavirus (HPV) screening followed by visual inspection after application of acetic acid (VIA) with same day treatment of eligible patients”. This study piloted this concept. Methods:in this prospective, cohort study, 98 WLHIV had HPV and VIA screening for cervical precancer lesions in a HIV clinic in Nigeria. Participants positive to HPV and/or VIA had biopsies from the visible lesions or quadrant of transformation zone. Participants positive to VIA and/or HPV16 or HPV18/45 had same-day thermal ablation treatment and the number of cases documented. The HPV, VIA and scenario of HPV followed by VIA results were compared with histologically confirmed cervical lesion grade 2 or worse statistically. Results:same day treatment was achieved in 95.0% of eligible cases. Statistically, sensitivity and specificity of VIA was 25.0% and 50.0% and HPV had 95.5% and 75.0%, respectively. In the HPV screening with VIA triage, sensitivity dropped to 45.5% but specificity improved to 100.0%. Conclusion:triaging HPV positive test with VIA for same-day treatment in cervical precancer screening among PLWHIV looks feasible. The improved specificity will reduce the overtreatment rate, loss to follow-up associated with repeat clinic visits and improve completion of continuum of care.

BackgroundColposcopy diagnosis and directed biopsy are the key components in cervical cancer screening programs. However, their performance is limited by the requirement for experienced colposcopists. This study aimed to develop and validate a Colposcopic Artificial Intelligence Auxiliary Diagnostic System (CAIADS) for grading colposcopic impressions and guiding biopsies.MethodsAnonymized digital records of 19,435 patients were obtained from six hospitals across China. These records included colposcopic images, clinical information, and pathological results (gold standard). The data were randomly assigned (7:1:2) to a training and a tuning set for developing CAIADS and to a validation set for evaluating performance.ResultsThe agreement between CAIADS-graded colposcopic impressions and pathology findings was higher than that of colposcopies interpreted by colposcopists (82.2% versus 65.9%, kappa 0.750 versus 0.516,p p p > 0.05). The CAIADS also demonstrated a superior ability in predicting biopsy sites, with a median mean-intersection-over-union (mIoU) of 0.758.ConclusionsThe CAIADS has potential in assisting beginners and for improving the diagnostic quality of colposcopy and biopsy in the detection of cervical precancer/cancer.

Background Human papillomavirus vaccine (HPV) impact on cervical precancer (cervical intraepithelial neoplasia grades 2+ [CIN2+]) is observable sooner than impact on cancer. Biopsy-confirmed CIN2+ is not included in most US cancer registries. Billing codes could provide surrogate metrics; however, the International Classification of Diseases, ninth (ICD-9) to tenth (ICD-10) transition disrupts trends. We built, validated, and compared claims-based models to identify CIN2+ events in both ICD eras. Methods A database of Davidson County (Nashville), Tennessee, pathology-confirmed CIN2+ from the HPV Vaccine Impact Monitoring Project (HPV-IMPACT) provided gold standard events. Using Tennessee Medicaid 2008-2017, cervical diagnostic procedures (N = 8549) among Davidson County women aged 18-39 years were randomly split into 60% training and 40% testing sets. Relevant diagnosis, procedure, and screening codes were used to build models from CIN2+ tissue diagnosis codes alone, least absolute shrinkage and selection operator (LASSO), and random forest. Model-classified index events were counted to estimate incident events. Results HPV-IMPACT identified 983 incident CIN2+ events. Models identified 1007 (LASSO), 1245 (CIN2+ tissue diagnosis codes alone), and 957 (random forest) incident events. LASSO performed well in ICD-9 and ICD-10 eras: 77.3% (95% confidence interval [CI] = 72.5% to 81.5%) vs 81.1% (95% CI = 71.5% to 88.6%) sensitivity, 93.0% (95% CI = 91.9% to 94.0%) vs 90.2% (95% CI = 87.2% to 92.7%) specificity, 61.3% (95% CI = 56.6% to 65.8%) vs 60.3% (95% CI = 51.0% to 69.1%) positive predictive value, 96.6% (95% CI = 95.8% to 97.3%) vs 96.3% (95% CI = 94.1% to 97.8%) negative predictive value, 91.0% (95% CI = 89.9% to 92.1%) vs 88.8% (95% CI = 85.9% to 91.2%) accuracy, and 85.1% (95% CI = 82.9% to 87.4%) vs 85.6% (95% CI = 81.4% to 89.9%) C-indices, respectively; performance did not statistically significantly differ between eras (95% confidence intervals all overlapped). Conclusions Results confirmed model utility with good performance across both ICD eras for CIN2+ surveillance. Validated claims-based models may be used in future CIN2+ trend analyses to estimate HPV vaccine impact where population-based biopsies are unavailable.

Persistent high-risk human papillomavirus (HPV) infections causes cervical precancer. HPV vaccination decreases the risk of cervical pre-cancer by up to 99%. The rate of vaccine uptake remains low. In KK Women’s and Children’s Hospital (KKH) C Clinic, the rate of eligible patients vaccinated is 5.3% and only 6.5% of eligible patients were offered the vaccine. The HPV vaccine taskforce aimed to increase the rates of eligible patients vaccinated and offered the vaccine. Factors leading to low uptake rates were identified and included the lack of awareness, lack of information, cost and accessibility issues. Accessibility issues were addressed by making vaccines available in clinic. Prices of the vaccines were subsidised, claims were made easier and consultation charges were waived. Education sessions were conducted for staff. In-house pamphlets and posters were developed and reminders were placed in clinic waiting areas. The electronic documentation was modified to include HPV vaccination. The Ministry of Health in Singapore also implemented a free opt-in HPV vaccination programme for secondary school girls. An audit was conducted over 6 months to assess rates of vaccination. The rate of eligible patients being offered the HPV vaccine in KKH C Clinic increased from 6.5% to 27.7% (p The HPV vaccine taskforce was effective in improving rates of HPV vaccination and patient awareness of the HPV vaccine. With this project, coupled with changes in Singapore’s health policies and attitudes of the population, we may one day eradicate cervical cancer.

Cervical cancer is the fourth most common cancer among women and still one of the major causes of women’s death around the world. Early screening of high grade Cervical Intraepithelial Neoplasia (CIN), precursors to cervical cancer, is vital to efforts aimed at improving survival rate and eventually eliminating cervical cancer. Visual Inspection with Acetic acid (VIA) is an assessment method which can inspect the cervix and potentially detect lesions caused by human papillomavirus (HPV), which is a major cause of cervical cancer. VIA has the potential to be an effective screening method in low resource settings when triaged with HPV test, but it has the drawback that it depends on the subjective evaluation of health workers with varying levels of training. A new deep learning algorithm called Automated Visual Evaluation (AVE) for analyzing cervigram images has been recently reported that can automatically detect cervical precancer better than human experts. In this paper, we address the question of whether mobile phone-based cervical cancer screening is feasible. We consider the capabilities of two key components of a mobile phone platform for cervical cancer screening: (1) the core AVE algorithm and (2) an image quality algorithm. We consider both accuracy and speed in our assessment. We show that the core AVE algorithm, by refactoring to a new deep learning detection framework, can run in ~30 seconds on a low-end smartphone (i.e. Samsung J8), with equivalent accuracy. We developed an image quality algorithm that can localize the cervix and assess image quality in ~1 second on a low-end smartphone, achieving an area under the ROC curve (AUC) of 0.95. Field validation of the mobile phone platform for cervical cancer screening is in progress.

Cervical cancer is one of the most common malignant ones among women worldwide. Visual examination of the cervix using acetic acid or Lugol’s iodine has been widely adopted in cervical cancer screening. However, there also exist problems of high misdiagnosis and low diagnostic efficiency during the manual screening of cervical images. Here, we present a new method for automatic cervical intraepithelial neoplasia (CIN) classification combining acetic acid and Lugol’s iodine cervigrams. We take use of convolutional neural network (CNN) and bi-directional long short-term memory (BiLSTM) to extract the maximum acetic acid images’ features and temporal characteristics, and then collect spatial features for Lugol’s iodine cervigrams. Meanwhile, we design a feature fusion module to combine features of different dimensions in cervigrams to further enhance the predictive performance. The experimental results indicated that the current method achieves an accuracy of 96.04%, which is superior to previous related works and those observed by clinicians. Our work will help to enhance the early detection of cervical cancers.

Background New guidelines for managing cervical precancer among women in the United States use risk directly to guide clinical actions for individuals who are being screened. These risk-based management guidelines have previously only been based on risks from a large integrated healthcare system. We present here data representative of women of low income without continuous insurance coverage to inform the 2019 guidelines and ensure applicability. Objective We examined the risks of high-grade precancer after human papillomavirus and cytology tests in underserved women and assessed the applicability of the 2019 guidelines to this population. Study Design We examined cervical cancer screening and follow-up data among 363,546 women enrolled in the Centers for Disease Control and Prevention’s National Breast and Cervical Cancer Early Detection Program from 2009 to 2017. We estimated the immediate (prevalent) risks of cervical intraepithelial lesion grade 3 or cancer by using prevalence-incidence mixture models. Risks were estimated for each combination of human papillomavirus and cytology result and were stratified by screening history. We compared these risks with published estimates used in new risk-based management guidelines. Results Women who were up-to-date with their screening, defined as being screened with cytology within the past 5 years, had immediate risks of cervical intraepithelial neoplasia grade 3 or higher similar to that of women at Kaiser Permanente Northern California, whose data were used to develop the management guidelines. However, women in the Centers for Disease Control and Prevention’s National Breast and Cervical Cancer Early Detection Program had greater immediate risks if they were never screened or not up-to-date with their screening. Conclusion New cervical risk–based management guidelines are applicable for underinsured and uninsured women with a low income in the United States who are up-to-date with their screening. The increased risk observed here among women who received human papillomavirus–positive, high-grade cytology results, who were never screened, or who were not up-to-date with their cervical cancer screening, led to a recommendation in the management guidelines for immediate treatment among these women.

Objectives The history of the diagnosis and treatment of cervical precancer is fragmentary. Findings in the English-speaking and German-speaking areas vary considerably. We aim to describe the history of clinical advances in diagnosis and treatment of cervical precancer and identify areas where further work is required. Study design We conducted a search of PubMed and Google Scholar. Full article texts were reviewed. Reference lists were screened for additional articles and books. 9 basic articles in German and 13 basic articles in books were identified. Results The first images of the ectocervix were published by H. Lebert (1812–1879) in the middle of the nineteenth century. R. Meyer's (1864–1947) theory of erosions, which dominated cervical pathology in the nineteenth century, was later refuted in studies by C. A. Ruge (1846–1926) and J. Veit (1852–1917). In 1908 W. Schauenstein (1870–1943) recognized the step-by-step development of cervical cancer. H. Hinselmann (1884–1959) replaced the purely histopathological approach previously with the use of colposcopy. All conization methods applied today can be traced back to amputation of the ectocervix as first indicated by J. Marion Sims (1813–1883) in 1861. In 1928 M. N. Hyams was the first to describe an excision method that employed electrodiathermy. The method of cold knife conization is based on a publication by J.W. Scott from 1957. The final breakthrough to effective electrodiathermy was achieved with the publications of W. Prendiville. Conclusions This paper is a step toward a better understanding of what we think and do today based on past findings of colposcopists and gynecopathologists.

Pap smear is a cytological examination to detect cells from the surface of cervical epithelium and cervical canal which aims to find cervical precancer lesions in order not to develop into cervical cancer in the future and adequate treatment (Amni, 2014). The phenomenon found in Awal Bros Pekanbaru Hospital Polyclinic, lack of willingness Mother doing pap smear examination. This study aims to determine the factors associated with the examination of pap smears in mothers in Obstetric Polyclinic Hospital Awal Bros Pekanbaru. The design used is descriptive correlative with cross sectional approach. The sample of this study consisted of 199 mothers. The data analysis showed that there was a correlation between knowledge (p value 0,001), attitude (p value 0,001) and husband support (p value 0,001) to pap smear examination. In this research the researcher suggest mother to increase knowledge about pap smear examination, embody mother trust to do pap smear examination and increase and maintain support from husband so that mother can do pap smear examination.

The pathology of cervical neoplasia provides the best model for integrating the morphologic basis for diagnosis with the molecular pathogenesis of human papillomavirus (HPV) induced precancer and cancer. This chapter focuses on the process of clinical screening and diagnosis and how a contemporary understanding of HPV biology informs morphologic diagnostic criteria in both cytology and histopathology. The science has also led to refinement in classification systems and improved diagnostic tests based on HPV and related biomarkers.

ObjectiveRecent studies reported a lower human papillomavirus 16 (HPV16) prevalence in cervical precancer among African American than Caucasian women in the general population. We assessed this relationship in women with HIV.DesignWomen living with or at risk for HIV in the Women's Interagency HIV Study were followed semi-annually with Pap tests, colposcopy/histology (if indicated), and collection of cervicovaginal lavage samples for HPV testing by PCR. Racial and ethnic groups were defined using genomic Ancestry Informative Markers (AIMs).ResultsAmong 175 cases of cervical intraepithelial neoplasia 3 or worse (CIN-3+), 154 were diagnosed in women with HIV. African American (27%) and Hispanic (37%) cases were significantly less likely than Caucasian (62%) women to test positive for HPV16 (P = 0.01). In multivariate logistic regression models, these associations remained significant for African Americans (odds ratio = 0.13; 95% confidence interval (CI) 0.04-0.44; P = 0.001) but not Hispanics, after controlling for HIV status, CD4 count, history of AIDS, age, smoking, and sexual behavior. Limiting the analysis to women with HIV did not change the findings.ConclusionHPV16 prevalence is lower in African American compared with Caucasian women with HIV and cervical precancer, independent of immune status. Future studies to determine why these racial differences exist are warranted, and whether there are similar associations between race and invasive cervical cancer in women with HIV. Further, HPV types not covered by quadrivalent and bivalent vaccines may play an especially important role in cervical precancer among HIV-positive African American women, a possible advantage to using nonavalent HPV vaccine in this population.

Barriers to access for cervical precancer care in low-resource settings go beyond cost. Gas-based cryotherapy has emerged as the standard treatment in these areas, but there are barriers to this technology that have necessitated the development and implementation of affordable and portable alternatives. This review identifies knowledge gaps with regard to technologies primarily used in low-resource settings, including standard cryotherapy, nongas-based cryotherapy, and thermoablation. These gaps are addressed using evidence-based guidelines, patient and provider acceptability, long-term obstetric outcomes, and treatment of women with HIV infection. This review highlights the need for prospective studies that compare ablative methods, especially given the increasing use of thermoablation.

BackgroundThis research fuses the experiences of a precancer diagnosis with the decision-making surrounding a vaccine that can protect against human papillomavirus strains that women may not have been exposed to. The interviewee cohort is of note as half the women were in their 30s and 40s and 75% were over the age of 26. These groupings are often overlooked in media discourses and narrative research surrounding human papillomavirus and the human papillomavirus vaccine.PurposeWomens’ diagnoses and treatment experiences, including colposcopies, biopsies, and Loop Electrosurgical Excision Procedures, are chronicled to highlight a liminal, precancerous state—one in which they are not deemed healthy, but nor have they been diagnosed with cancer. These are emotion-filled experiences that are ridden with anxiety and fear, but also ones that are structured with self-care strategies to contain human papillomavirus infections and the risk of cervical cancer.MethodsTwenty women who attended Sunnybrook Health Sciences Centre’s human papillomavirus vaccination clinic were interviewed and their narratives were documented and analyzed to determine their experiences surrounding human papillomavirus infections and precancer as well as their motivations for human papillomavirus vaccination.ResultsThe decision to undergo human papillomavirus vaccination was a self-care strategy that accompanied treatment procedures and was a means to reduce cervical cancer risk. While encouraged with the human papillomavirus vaccine’s potential to curb cervical cancer, they had a tempered view of the vaccine and its effectiveness in their cases, given their medical histories.ConclusionsThe research provides an in-depth accounting of an often overlooked grouping in human papillomavirus and human papillomavirus vaccination research and media discourse which, generally, focuses upon middle-school-aged girls and university-/college-aged women. In addition, the research provides recommendations for practice for cervical precancer diagnoses going forward.

The COVID-19 pandemic has a major impact on a wide range of health outcomes. Disruptions of elective health services related to cervical screening, management of abnormal screening test results, and treatment of precancers, may lead to increases in cervical cancer incidence and exacerbate existing health disparities. Modeling studies suggest that a short delay of cervical screening in subjects with previously negative HPV results has minor effects on cancer outcomes, while delay of management and treatment can lead to larger increases in cervical cancer. Several approaches can mitigate the effects of disruption of cervical screening and management. HPV-based screening has higher accuracy compared to cytology, and a negative HPV result provides longer reassurance against cervical cancer; further, HPV testing can be conducted from self-collected specimens. Self-collection expands the reach of screening to underserved populations who currently do not participate in screening. Self-collection and can also provide alternative screening approaches during the pandemic because testing can be supported by telehealth and specimens collected in the home, substantially reducing patient-provider contact and risk of COVID-19 exposure, and also expanding the reach of catch-up services to address backlogs of screening tests that accumulated during the pandemic. Risk-based management allows prioritizing management of patients at highest risk of cervical cancer while extending screening intervals for those at lowest risk. The pandemic provides important lessons for how to make cervical screening more resilient to disruptions and how to reduce cervical cancer disparities that may be exacerbated due to disruptions of health services.

Purpose Despite improvement in vaccines against human papilloma virus (HPV), the causative agent of cervical cancer, screening women for cervical precancer will remain indispensable in the coming 3040 years. A simple test that could be performed at home or at a doctors practice and that informs the woman whether she is at risk would significantly help make a broader group of patients who aware that they need medical treatment. Cervical vaginal fluid (CVF) is a body fluid that is very well suited for such a test. Methods Narrative review of cervical (pre)cancer candidate biomarkers from cervicovaginal fluid, is based on a detailed review of the literature. We will also discuss the possibilities that these biomarkers create for the development of a self-test or point-of-care test for cervical (pre)cancer. Results Several DNA, DNA methylation, miRNA, and protein biomarkers were identified in the cervical vaginal fluid; however, not all of these biomarkers are suited for development of a simple diagnostic assay. Conclusions Proteins, especially alpha-actinin-4, are most suited for development of a simple assay for cervical (pre)cancer. Accuracy of the test could further be improved by combination of several proteins or by combination with a new type of biomarker, e.g., originating from the cervicovaginal microbiome or metabolome.

Cervical cancer is the fourth leading cause of cancer-related death in women worldwide, with 90% of cases occurring in low- and middle-income countries (LMICs). There has been a global effort to increase access to affordable screening in these settings; however, a corresponding increase in availability of effective and inexpensive treatment modalities for ablating or excising precancerous lesions is also needed to decrease mortality. This article reviews the current landscape of available and developing technologies for treatment of cervical precancer in LMICs. At present, the standard treatment of most precancerous lesions in LMICs is gas-based cryotherapy. This low-cost, effective technology is an expedient treatment in many areas; however, obtaining and transporting gas is often difficult, and unwieldy gas tanks are not conducive to mobile health campaigns. There are several promising ablative technologies in development that are gasless or require less gas than conventional cryotherapy. Although further evaluation of the efficacy and cost-effectiveness is needed, several of these technologies are safe and can now be implemented in LMICs. Nonsurgical therapies, such as therapeutic vaccines, antivirals, and topical applications, are also promising, but most remain in early-stage trials. The establishment of evidence-based standardized protocols for available treatments and the development and introduction of novel technologies are necessary steps in overcoming barriers to treatment in LMICs and decreasing the global burden of cervical cancer. Guidance from WHO on emerging treatment technologies is also needed.

Cervical cancer incidence and mortality rates remain high in medically underserved areas. In this study, we present a low-cost (ex vivo and in vivo pilot studies; results demonstrate that the confocal microendoscope can enhance visualization of nuclear morphology, contributing to significantly improved recognition of clinically important features for detection of cervical precancer.

Introduction: Human papillomavirus (HPV) is the most common viral infection of the reproductive tract. The persistent infection of high-risk HPV (hrHPV) is associated with cervical cancer. There exists a trend from no hrHPV genotyping, to partial and expanded hrHPV genotyping for the primary screening of cervical precancer. Areas covered: The authors first review HPV assays for screening use on the market. Then, they describe and compare the Zeesan MeltPro® HPV genotyping assay, a semi-automated full hrHPV genotyping assay working on a real-time PCR platform. Based on multicolor melting curve analysis, this assay allows individual identification of 14 hrHPV genotypes in a single reaction. Expert opinion: MeltPro® HPV genotyping assay provides a flexible choice for both high- and low-throughput screening. It is robust in diverse settings ranging from remote and underdeveloped areas to large screening centers. Extra merits such as low cost and ease-of-use would facilitate its implementation in cervical precancer screening, control, and prevention.

Simple Summary Persistent high-risk human papillomavirus (HPV) infection can lead to cervical precancer and cancer. Recently, HPV testing has been introduced for primary cervical screening, but the HPV DNA test cannot distinguish between transient and persistent HPV infection. Thus, there is an unmet clinical need to develop a new test to identify women with a high-risk persistent HPV infection. Raman spectra were recorded from cervical smear samples (n = 60) and, on the basis of HPV DNA and HPV mRNA test results, a classifier was developed to identify persistent HPV infection. A further blinded independent test set (n = 14) was used to validate the model, and sensitivity of 90% and specificity of 100% were achieved. Improved triage would allow women with a high-risk persistent HPV infection to be referred for immediate treatment, while women with a low-risk transient infection could avoid overtreatment. Abstract The role of persistent high-risk human papillomavirus (HPV) infection in the development of cervical precancer and cancer is now well accepted, and HPV testing has recently been introduced for primary cervical screening. However, the low specificity of HPV DNA testing can result in large numbers of women with an HPV-positive result, and additional triage approaches are needed to avoid over-referral to colposcopy and overtreatment. The aim of this study was to assess Raman spectroscopy as a potential triage test to discriminate between transient and persistent HPV infection. HPV DNA status and mRNA status were confirmed in ThinPrep® cervical samples (n = 60) using the Cobas 4800 and APTIMA HPV test, respectively. Raman spectra were recorded from single-cell nuclei and subjected to partial least squares discriminant analysis (PLSDA). In addition, the PLSDA classification model was validated using a blinded independent test set (n = 14). Sensitivity of 85% and specificity of 92% were achieved for the classification of transient and persistent HPV infection, and this increased to 90% sensitivity and 100% specificity when mean sample spectra were used instead of individual cellular spectra. This study showed that Raman spectroscopy has potential as a triage test for HPV-positive women to identify persistent HPV infection.

Background Urine testing for high-risk human papillomavirus (HR-HPV) detection could provide a non-invasive, simple method for cervical cancer screening. Objectives We examined whether HR-HPV detection is affected by urine collection time, portion of urine stream, or urine fraction tested, and assessed the performance of HR-HPV testing in urine for detection of cervical intraepithelial neoplasia grade II or worse (CIN2+). Study design A total of 37 female colposcopy clinic attendees, ≥30 years, provided three urine samples: “first void” urine collected at home, and “initial stream” and “mid-stream” urine samples collected at the clinic later in the day. Self- and physician-collected brush specimens were obtained at the same clinic visit. Colposcopy was performed and directed biopsies obtained if clinically indicated. For each urine sample, HR-HPV DNA testing was conducted for unfractionated, pellet, and supernatant fractions using the Trovagene test. HR-HPV mRNA testing was performed on brush specimens using the Aptima HPV assay. Results HR-HPV prevalence was similar in unfractionated and pellet fractions of all urine samples. For supernatant urine fractions, HR-HPV prevalence appeared lower in mid-stream urine (56.8%[40.8–72.7%]) than in initial stream urine (75.7%[61.9–89.5%]). Sensitivity of CIN2+ detection was identical for initial stream urine and physician-collected cervical specimen (89.9%[95%CI = 62.7–99.6%]), and similar to self-collected vaginal specimen (79.1%[48.1–96.6%]). Conclusion This is among the first studies to compare methodologies for collection and processing of urine for HR-HPV detection. HR-HPV prevalence was similar in first void and initial stream urine, and was highly sensitive for CIN2+ detection. Additional research in a larger and general screening population is needed.

Background This study aimed to evaluate the clinical performance of p16/Ki-67 dual staining in the detection of cervical intraepithelial neoplasia grade 2 or 3 or worse (CIN2+/CIN3+) in Chinese women. Methods Cervical exfoliated cells were collected from 537 eligible women and were used for liquid-based cytology (LBC), p16/Ki-67 dual staining, and human papillomavirus (HPV) DNA testing. All women received colposcopy with biopsies taken at abnormal sites. Histopathological diagnoses were used as the gold standard. Results p16/Ki-67 staining had a positivity rate of 43.58% overall; the rate increased significantly with histological severity (p0.001). The sensitivities of p16/ki-67 for detecting CIN2+ and CIN3+ were 88.10% and 91.30%, respectively. Compared with high-risk HPV (HR-HPV), sensitivity of p16/Ki-67 was lower for detecting CIN2+ (88.10% versus 95.71%), but similar for detecting CIN3+ (91.30% versus 96.27%). Specificities of p16/Ki-67 were 85.02% for detecting CIN2+ and 76.86% for detecting CIN3+, values similar to those for LBC (84.71% for CIN2+, 80.05% for CIN3+) but higher than those for HR-HPV (62.77% for CIN2+, 71.25% for CIN3+). All the tests performed better in women30 years. With respect to the performance of triage for women with ASC-US, sensitivities of p16/Ki-67 were 86.36% for detecting CIN2+ and 83.33% for detecting CIN3+, values similar to those of HR-HPV. However, specificities of p16/Ki-67 were both higher than those of HR-HPV (85.96% versus 67.54% for CIN2+, 79.84% versus 62.90% for CIN3+). Conclusion P16/Ki-67 dual staining could probably provide an optional method for China's national cervical cancer screening, and could also be considered as an efficient method of triage for managing women with ASC-US.

HPV testing is a better alternative for cervical cancer screening, but additional procedures are required for triage of HPV positive women. HPV encoded oncoproteins E6 and E7, as the main effectors of HPV carcinogenicity represent promising triage alternatives. To evaluate performance of the test, we included 155 women from a screening study and 59 from the same referral population attending colposcopy and with precancerous lesions. All were HPV-tested with HC2 and genotyped with LiPA, and cervical swabs were tested for HPV16/18 E6 oncoproteins. Histologic specimens were reviewed and adjudicated using p16 immunohistochemistry and 55 women had confirmed histologic HSIL, 31 (56.3%) associated with HPV 16/18, 23 with other HPV types and one HPV negative. Sensitivity and specificity were estimated with histologic HSIL/cancer as gold standard. E6 oncoprotein was detectable in all but one HSIL and in all cancers where HPV16/18 DNA was detected, but in none of the cases associated with other HPV types or HPV negatives. Among the few HPV16/18 DNA positive subjects initially without HSIL (n = 4) who were E6 oncoprotein positive, precancer was detected during follow-up in 2 out of 3 with available information. Estimated sensitivity for HPV16/18-related HSIL+ was 96.8% (95%CI = 83.8-99.8) and for all HSIL+ regardless of HPV type it was 56.4% (95%CI = 43.3-68.6). Specificity was 97.5% (95%CI = 93.7-99.0). E6 oncoprotein proved as a highly sensitive and specific marker for detection of HPV16/18-related HSIL lesions in this Honduran population with limited previous screening and may be useful as a triage method in screening programs, particularly in low income countries.

Women previously vaccinated against human papillomavirus (HPV) type 16 and 18 are now reaching the age (21 years) at which cervical-cancer screening is recommended in the U.S. The impact of HPV vaccination on risks of cervical precancer following a positive and negative screen among women aged 21-24 years who just started routine cervical screening are not well described. Therefore, three-year absolute and relative (RR) cumulative risks of cervical intraepithelial neoplasia grade 2 or more severe diagnoses (≥CIN2) and grade 3 or more severe diagnoses (≥CIN3) were estimated for women undergoing cervical screening at Kaiser Permanente Northern California. Risks were estimated in women aged 21-24 years (n = 75,008) undergoing cervical screening since late 2006, 6 months after HPV vaccination became available; women were categorized vaccinated at ages18, 18-20, and 21-24 years and compared to those who were unvaccinated. Three-year risks were estimated for normal, low-grade, and high-grade cytology results. Three-year risks of ≥CIN2 and ≥CIN3 for unvaccinated women following low-grade cytology were 10.89% for and 3.70%, respectively. By comparison, Three-year risks of ≥CIN2 and ≥CIN3 were 5.26% (RR = 0.48, 95%CI = 0.24-0.99) and 0.99% (RR = 0.27, 95%CI = 0.06-1.13), respectively, for women vaccinated under the age of 18 years. Three-year ≥CIN2 and ≥CIN3 risks were lower for those HPV vaccinated at younger age for any screening result (p

Objective This study aimed to establish the noninferiority of a single-freeze application with CO2 or N2O compared with the standard double freeze with N2O for cryotherapy treatment. Materials and methods Sixty women undergoing hysterectomy for reasons other than cervical cancer or precancer were randomized to 1 of 3 techniques as follows: (1) double freeze with N2O, (2) single freeze with N2O, or (3) single freeze with CO2. The cervix was separated and cut into anterior and posterior segments, and the deepest area of necrosis was recorded. Comparisons were made using regression analysis. The margin of noninferiority was defined as 0.8 mm. Results On the anterior lip, a single freeze with N2O was noninferior to a double freeze of the same gas, but on the posterior lip, the single freeze was not. The single freeze of CO2 did not provide sufficient depth of necrosis in either lip to infer noninferiority versus the double freeze with N2O. Conclusions A single freeze with N2O is noninferior to a double-freeze technique in the anterior but not the posterior lip. However, the result for posterior lips was close to reaching statistical significance. In addition, CO2 had approximately 1 mm shallower depth of necrosis compared with N2O techniques; however, the clinical implications are unknown. Given the extensive use of CO2 globally, further clinical evaluation is needed.

Introduction: Colposcopy is an important tool in the diagnosis of cervical precancer and early cancer. The assessment of women with abnormal cytology and selection of those who require further therapy or follow up depends on the colposcopic assessment of the Transformation Zone (TZ). Identification of the TZ is thus an important part of this examination. Intra and inter-observer variability is known to be relatively high in the colposcopic interpretation of abnormal features. However, there are hardly any studies on the observer variability in the assessment of the type of TZ. Aim: The present study was conducted with the aim to compare the intra and inter-observer variability of the TZ type classification and the Squamo-Columnar Junction (SCJ) visibility and to quantitatively measure the intra and inter-observer correlations of tracing of the TZ contours. Materials and Methods: Colposcopy images were obtained for a total of 170 cases. They were reviewed by three colposcopists independently. The colposcopists classified the TZ type and also marked the SCJ contours on the images. Each observer independently reviewed the cases on two different instances (few weeks apart) and the result was compiled for intra-observer variation. The intra and inter observer variability on the TZ type was compared using Cohen’s Kappa. This was followed by a quantitative measurement of TZ observation variability using Hausdorff distance. Results: The inter-observer agreement for the TZ type classification was moderate (Kappa= 0.53 to 0.66). The Intra-observer agreement was moderate to strong (0.60 to 0.86). Conclusion: Colposcopic in vivo examination increases the variability in the identification of the TZ when compared to the analysis of recorded images. The disagreement in the TZ type was mostly in categories Type 2 vs Type 3 followed by Type 1 vs Type 2. A computerized quantification method can be used for quality control and training purpose in colposcopy.

Interview with Attila Lorincz by Claire Raison (Commissioning Editor)To mark the beginning of the 15th year of Expert Review of Molecular Diagnostics, the journal’s Editor-in-Chief shares his expert knowledge on translational diagnostics, his opinion on recent controversies and his predictions for molecular diagnostics in 2015 and beyond.Attila Lorincz received his doctorate from Trinity College, Dublin, Republic of Ireland, and went on to become a research fellow at the University of California, Santa Barbara, CA, USA. During Professor Lorincz’s research on human papillomavirus (HPV), he found several important and novel carcinogenic HPV types and pioneered the use of HPV DNA testing for clinical diagnostics. In 1988, Professor Lorincz’s team produced the first HPV test to be FDA-approved for patients and in 2003, for general population cervical precancer screening. Now Professor of Molecular Epidemiology at the Centre for Cancer Prevention, Queen Mary University of London, UK, he and his team are furthe...