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With a goal to increase the percentage of grid energy produced by renewable sources, research and development efforts in solar, wind, and geothermal resources are progressing rapidly. In this work, the use of concentrated solar thermal power for energy production and thermal energy storage is presented for the supercritical carbon dioxide (sCO2) Brayton cycle. The use of sCO2 as the working fluid for concentrated solar thermal power generation allows for greater power output potential at a smaller footprint compared to steam power cycles. The present work is targeted at the design of next generation solar thermal receivers for such power cycles. The target design conditions for an sCO2 receiver for next-generation utility scale power generation systems include a design pressure of 200 bar, a fluid outlet temperature of 720C, and an incident concentrated flux surface of 100 W/cm2. The receiver must operate at these conditions for a 30 year lifetime. To operate at the needed high temperature and pressure conditions for next-generation sCO2 power cycles, the central receiver of the solar power plant needs to be made from a high temperature and high pressure materials such as nickel superalloys. The manufacturing method of the solar thermal receiver becomes important as both pressure stresses and thermal stresses act on the internal features of the solar receiver. In prior work by the group, a microscale pin array receiver was developed and fabricated using microlamination methods. This fabrication method restricted the size of the unit cell of the pin array to 2.5 cm, requiring an elaborate and heavy header structure to route fluid in and out of multiple parallel unit cell pin array panels that comprise the central receiver. Headers were brazed to the diffusion-bonded core to bring fluid into and out of the unit cells. Several fabrication challenges were faced in the development of this design, including leaks in the brazed joints. Odele [30] showed, by numerical modeling, that by using metal Additive Manufacturing (AM), one could design longer unit cell pin arrays, that operate at similar efficiencies as the microlaminated design, resulting in a lighter header structure. Furthermore, the pin array core and headers could be built as a single panel monolithically, resulting in the elimination of braze joints.In this thesis, detailed design of the header and its interface with the pin array core is developed. The design goals are to reduce weight of the microlamination-based headers, reduce stresses due to the high pressure and temperature, and design for maximal receiver life to 100,000 hours. The pin array core and the headers would constitute a unit cell panel. The panel would need to be designed to allow for placement of several panels in parallel without uncooled regions being directly exposed to the intense concentrated solar radiation in a power tower configuration. The receiver pin array core makes use of correlations from previously validated experimental data. An iterative design campaign is performed using simulations in Ansys mechanical to meet the pressure stress design requirement of 150 MPa. After eliminating stress regions exceeding the design parameters, simulations were performed in Ansys Fluent to ensure that the flow from the headers to the pin array core was uniformly distributed and to confirm that the pressure drop was below 2% through the panel. The design was subsequently printed by the Rollett group at the NEXT Manufacturing Center at Carnegie Mellon University. The prototype was heat treated and pressure tested at operating temperatures at the UC Davis STEEL facility. Results of static and limited cyclic pressure testing at temperature indicate that a leak-free panel of the design can be fabricated using metal AM. Thermal stress simulations were performed on the receiver showing a few locations with high points. To mitigate these stresses, design changes were considered to insulate the outer edges and corners of the receiver from direct insolation.

Objectives Extended high-risk human papillomavirus (hrHPV) genotype testing has recently been introduced in routine cervical cancer screening. Changes in national and regional hrHPV genotype prevalence offer an objective baseline indicator of the future impact of mass HPV vaccination and HPV-based cervical screening. Methods This retrospective study reports nationwide hrHPV genotyping results from July 2018 to June 2019 in 29 KingMed Diagnostics laboratories throughout China. Results In total, 2,458,227 hrHPV genotyping results were documented from KingMed’s nationwide laboratory database during the study period. The overall prevalence of hrHPV-positive results was 19.1%, with twin peaks for highest hrHPV infection rates in women younger than 30 years of age (22.0%) and 50 years of age and older (21.8%). The most frequently detected hrHPV genotypes were HPV-52 (4.7%), HPV-16 (3.4%), HPV-53 (2.5%), HPV-58 (2.4%), HPV-51 (2.0%), and HPV-68 (1.6%). Overall, hrHPV-positive results varied regionally from 15.3% to 24.4%. Conclusions Nationwide hrHPV genotyping results from KingMed laboratories offer a baseline for measuring the future impact of large-scale HPV vaccination. High hrHPV infection rates in older (≥50 years) Chinese women likely reflect the limited extent of cervical screening in China. High rates of hrHPV infection and variable regional hrHPV genotype distribution may represent limiting factors for cost-effective implementation of hrHPV-based cervical screening in China.

Our aim was to conduct a large epidemiologic analysis of the distribution of human papilloma virus (HPV) genotypes associated with cervical neoplasias and cancers at a major Chinese gynecologic center. The pathologic database was searched for cervical histopathologic diagnoses with prior HPV genotyping from liquid cervical cytology specimens obtained ≤6 months before biopsy. HPV testing was performed by using the Tellgenplex HPV27 or YanengBio HPV23 genotyping assays. A total of 40 352 cases meeting study criteria were identified. High risk human papillomavirus (hrHPV) was detected in 94.1% of squamous cancers compared to in only 83.3% of cervical adenocarcinomas. The prevalence of multiple HPV infections was highest in cervical intraepithelial neoplasia 1 (CIN1) (33.8%) and decreased with increasing severity of squamous lesions. The distribution of HPV genotypes was similar between CIN1 and histopathologic-negative cases. HPV16 was one of the three most common hrHPV genotypes before all histopathologic abnormalities, ranging from 72.0% for cervical cancers, 38.7% for CIN2/3/AIS, 13.1% for CIN1, and 9.1% for biopsy-negative cases. HPV16 and HPV18 accounted for over 87.2% of detected hrHPV genotypes for all glandular intraepithelial neoplastic lesions and cancers, whereas squamous lesions did not show this pattern. 80.3% of cervical cancers were associated with genotypes covered by HPV16/18 vaccines and 89.6% with genotypes covered by 9-valent vaccination.

Introduction: Cervical screening has decreased the incidence of cervical carcinoma around the world primarily by preventing cervical squamous carcinoma, with significantly less measurable protective benefits in prevention of cervical adenocarcinoma. In this study, we apply Bayesian modeling of cervical clinical, screening, and biopsy data from a large integrated health system to explore the feasibility of calculating personalized risk assessments on screened system patients for subsequent histopathologic diagnoses of invasive cervical adenocarcinoma (AdCa) or cervical adenocarcinoma in situ (AIS). Materials and Methods: Diagnoses of cervical AIS or AdCa rendered between 2005 and 2018 were identified in our large health system database with 1,053,713 cytology results, 354,843 high-risk (hr) human papillomavirus (HPV) test results, and 99,012 cervical histopathologic results. Using our continuously updated Bayesian cervical cancer screening model which includes clinical data, cervical screening results, and cervical biopsy results, we projected quantitative estimates of patients’ 5-year cumulative risk for cervical AIS or AdCa. Results: 161 patients were identified with AIS (ages 17–75, mean 37 years), and 99 patients had diagnoses of cervical AdCa (ages 26–91, mean 48 years). Quantitative Bayesian 5-year cumulative risk projections for diagnoses of cervical AdCa or AIS in patients with different cervical screening test and biopsy histories were determined. The highest patient risk projections for subsequent cervical AdCa and/or AIS histopathologic diagnoses were associated with prior cervical screening test results of HPV-positive atypical glandular cells. Prior squamous cytologic abnormalities were associated with lower risk estimates. Prior histopathologic diagnoses of squamous abnormalities also influenced quantitative risk. A prior histopathologic diagnosis of AIS was associated with a very low risk of subsequent AdCa, consistent with effective excisional treatment. AdCa risk was greatest in women aged 30–65 years with prior CIN3 biopsy results, whereas AIS risk was greatest in women Conclusion: Prevention of cervical AdCa in screened patients remains a major challenge for cervical screening. Individualized risk projections for cervical glandular neoplasia reflecting patient age, prior cervical screening test results, and prior cervical biopsy history are feasible using Bayesian modeling of health system data.

Introduction High risk (hr) human papillomavirus (HPV) testing has been proposed as a possible replacement for Papanicolaou (Pap) cytology for cervical screening. The aim of the present study was to assess the hrHPV detection rates using 3 available Food and Drug Administration–approved HPV assays in patients with high-grade squamous intraepithelial lesion (HSIL) cytology results and to correlate the cervical screening test results with the immediate histopathologic findings. Materials and methods Cases with positive HSIL ThinPrep cytology findings, concurrent hrHPV testing results, and histopathologic follow-up results obtained within 6 months of the Pap/HPV co-testing were identified from July 2010 to April 2018. Results A total of 943 HSIL Pap tests were identified with adjunctive hrHPV co-testing, and hrHPV was detected in 883 (93.6%) of these 943 cases. Cervical intraepithelial neoplasia ≥2 (CIN2+) lesions were diagnosed in 71.5% of patients, including 3.2% with invasive squamous cell carcinoma (SCC). In all hrHPV testing platforms, the detection rate for CIN2+ was significantly greater for the patients with positive HPV testing (72.7%) than for those with negative HPV testing (53.4%). However, CIN2+ lesions, including 3 cases of SCC, were found in 24 of 45 women (53.4%) with HSIL Pap and negative HPV testing results. Conclusions The risk of CIN2+ histopathologic findings was significantly greater for patients with hrHPV-positive HSIL results. However, a subset of patients with HPV-negative HSIL results were found to have CIN2+ lesions, including SCC. The long-term effects of primary HPV screening on cervical cancer incidence, stage, and prognosis remain uncertain.

Objectives Extended testing for high-risk human papillomavirus genotypes (hrHPVGTs) is increasingly investigated for risk stratification in cervical cancer screening. Methods Age and hrHPVGT results from 16,993 women with atypical squamous cells of undetermined significance (ASC-US) cytology between November 2015 and August 2021 were studied and correlated with available histopathologic findings within 6 months. Results High-risk human papillomavirus (hrHPV)–positive rate was 66.9% in women with ASC-US cytology, and the most prevalent genotypes were HPV 52 (20.9%), 16 (15.7%), and 58 (12.8%). Single hrHPV genotypes and multiple HPV genotypes were detected in 77.2% and 22.8% of women with hrHPV-positive results. Cervical intraepithelial neoplasia grade 2 or more (CIN2+) severe lesions were identified in 19.5% of women with hrHPV-positive ASC-US. The greatest risk for CIN2+ was found in single genotype infections with HPV 16 (33.1%), followed by women with multiple genotype infections, including HPV 16 (32.7%), 82 (30.8%), and 31 (30.0%). hrHPVGT testing for genotypes 16, 31, 35, 45, 82, 58, 33, 52, and 18 was identified in 91.9% (965/1,050) of CIN2+ cases, with 88.9% sensitivity, 43.2% specificity, positive predictive value of 23.9%, and negative predictive value of 95.1%. Conclusions Extended hrHPV genotyping for women with ASC-US cytology could identify those hrHPV genotypes (HPV 16, 31, 35, 45, 82, 58, 33, 52, 18) associated with higher risk of CIN2+ and allows for refined risk stratification of women being screened.

Extended high-risk human papillomavirus (hrHPV) genotype testing (hrHPVGT) has emerged as a new strategy to help optimize the efficiency of hrHPV triage.Women with an atypical squamous cells of undetermined significance (ASC-US) cervical Papanicolaou test result who underwent hrHPVGT between October 2017 and May 2021 at the Obstetrics and Gynecology Hospital of Fudan University in Shanghai, China, were studied. For hrHPVGT, a proprietary multiplex real-time polymerase chain reaction assay was used. hrHPVGT and viral load test results in selected patients were correlated with histopathologic follow-up findings available within 6 months.In total, 17,235 women with ASC-US cytology who had hrHPVGT results were identified in the Obstetrics and Gynecology Hospital of Fudan University database. The hrHPV-positive rate was 61.8%, and the most prevalent hrHPV genotypes were type 52 (HPV52) (16%), HPV16 (11.3%), HPV58 (10.2%), and HPV53 (8.4%). Single hrHPV genotypes were detected in 65.9% of women with hrHPV-positive results, and multiple genotypes were detected in 34.1%. Histopathologic cervical findings within 6 months were available in 5627 hrHPV-positive women and 2223 hrHPV-negative women. High-grade cervical intraepithelial lesions or cervical cancer (cervical intraepithelial neoplasia 2 or greater [CIN2+]) were identified in 7.5% of hrHPV-positive women who had ASC-US cytology and in 0.9% of hrHPV-negative women who had ASC-US cytology. The greatest risk for CIN2+ was in single hrHPV genotype infections with HPV16 (21.1%), HPV33 (15.2%), HPV82 (10%), and HPV18 (9.9%). hrHPVGT for genotypes HPV16, HPV33, HPV82, HPV18, HPV31, HPV45, HPV58, and HPV52 identified 95% of CIN2+ cases with 90.8% sensitivity, 53.8% specificity, a positive predictive value of 10.2%, and a negative predictive value of 99%. A significantly increased viral load was associated only with women who had HPV16-related CIN2+.hrHPVGT for women who have ASC-US cytology allows for risk stratification capable of optimizing the efficiency of triage for hrHPV-positive women.

Introduction Our objective was to evaluate the impact on the incidence of cervical cancer in New Zealand of 5-yearly human papillomavirus (HPV) primary screening compared with 3-yearly cytology. Materials and methods Unbiased estimates of the screening test sensitivity of HPV and cytology screening, and screening coverage, were used to calculate the reduction in cervical cancer incidence obtained by current cytology screening and the new HPV screening policy. Results HPV screening in New Zealand is predicted to increase the incidence of cervical cancer in women being screened by 81.7% (95% CI: 38.9%-124.7%). The overall increase in the population incidence of cervical cancer in New Zealand was estimated to be 46.7% (95% CI 42.6%-50.8%), leading to about 57 more women developing cervical cancer each year. Conclusions The results indicate that lengthening the screening interval concurrently with changing to HPV testing may reduce the protection from invasive cervical cancer for women. Women in New Zealand should continue to be screened by cytology every 3 years. Changes to screening policy should be carefully designed so that changes in screening effectiveness can be accurately measured.

Objectives Since the publication of our study demonstrating high negative predictive values (>99% for women in their 40s) of benign-appearing endometrial cells (nEMCs), we have begun to include an educational comment in Papanicolaou (Pap) test reports with nEMCs that recommends routine periodic screening for asymptomatic premenopausal women (APW). The current study evaluated how the inclusion of this comment has affected clinical practice patterns at our institution. Methods The 2017 to 2019 database identified 175 reports containing the educational comment in women aged 45 to 54 years with a follow-up time of 11 to 37 months. Data, including age, menopause status, symptoms, imaging, and outcome, were collected. The procedure rate and the impact of clinical modifiers were assessed. Results Thirty-seven (20.6%) patients had biopsies within 6 months, which decreased from 48.1% as we previously reported. All nine (5%) APW with biopsies triggered only by nEMCs had benign histopathology. The remaining 28 biopsied patients had abnormal bleeding or a thickened endometrium, or they were postmenopausal, including a 53-year-old patient with complex atypical hyperplasia. None of the 138 patients with conservative follow-up developed atypical/malignant lesions. Conclusions A qualifying educational note included in Pap reports significantly reduced follow-up biopsies in APW. Optimal follow-up of nEMCs should be based on relevant clinical modifiers.

Background High-risk human papillomavirus (hrHPV) messenger RNA (mRNA) testing, the Food and Drug Administration-approved testing platform since 2013, has been increasing as a cervical screening alternative to hrHPV DNA testing methods. This study reports the largest routine clinical follow-up study reported to date of hrHPV mRNA cotesting and histopathologic follow-up results for women with high-grade squamous intraepithelial lesion (HSIL) cytology results. Methods HSIL Papanicolaou test results for women cotested with Aptima hrHPV mRNA testing between June 2015 and November 2020 were analyzed along with recorded histopathologic follow-up results within 6 months of screening. Results Aptima hrHPV mRNA-positive results were reported for 95.2% of the cotested HSIL cytology cases (905 of 951). Histopathologic cervical intraepithelial neoplasia grade 2 or worse (CIN2+) was diagnosed on follow-up in 538 of 701 hrHPV mRNA-positive cases (76.8%) and in 15 of 36 hrHPV mRNA-negative cases (41.7%). Additional reviews of the hrHPV mRNA-negative HSIL cases showed variable interpretations, and confirmatory blinded-review interpretations of HSIL or atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion were more likely in cases with histopathologic CIN2+ (77.5% [93 of 120]) than those with cervical intraepithelial neoplasia grade 1 or negative findings (63.1% [101 of 160]; P Conclusions This large routine-clinical-practice study confirms the previously reported high sensitivity of hrHPV mRNA testing for the detection of high-grade cervical dysplasia and cervical cancers. The blinded-review findings indicate that additional cytology review may be helpful for confirming an interpretation of HSIL in daily practice, especially for hrHPV-negative HSIL cases.

OBJECTIVES Cervical stenosis can jeopardize adequate posttreatment cytologic follow-up of patients treated for high-grade cervical intraepithelial lesions. An impact on human papillomavirus (HPV) testing has not been described. MATERIALS AND METHODS We describe 2 patients with cervical stenosis, followed by cytology and HPV co-testing after excisions of high-grade cervical intraepithelial lesions. Each had 1 or more co-test "double-negative" results. Hysterectomies revealed unexpected cervical carcinomas. RESULTS In case 1, an 80-year-old woman with complete cervical stenosis and earlier high-grade squamous dysplasia presented with abdominal pain, nausea, and an enlarged uterus. Attempted endometrial biopsy was unsuccessful. Cytology and HPV tests 9 months earlier were negative. Hysterectomy revealed a cervical squamous carcinoma. In case 2, a 40-year-old woman followed conservatively after excision of endocervical adenocarcinoma in situ had 5 follow-up cytology and HPV co-tests. All were HPV negative. Elective hysterectomy revealed cervical adenocarcinoma. Both carcinomas tested HPV positive. CONCLUSIONS Cervical stenosis in women developing cervical cancer can cause misleading sampling and false-negative HPV test results.

ObjectivesGiven the recent debate challenging the contribution of cytology in cervical screening, we evaluated results of liquid-based cytology (LBC) and human papillomavirus (HPV) testing in cotesting preceding cervical cancer (CxCa) and precancer diagnoses in a national, heterogeneous population.MethodsWe assessed the results of cotesting, performed by Quest Diagnostics, in 13,633,071 women 30 years and older, tested 2010 to 2018. Cotest results preceding CxCa or precancer diagnoses were analyzed and stratified by histopathology.ResultsAmong all screening results, 1,615 cotests preceded 1,259 CxCa diagnoses, and 11,164 cotests preceded 8,048 cervical precancer diagnoses. More women who were subsequently diagnosed with CxCa within 1 year were identified by the LBC result than by the HPV result (85.1%, 1,015/1,193 vs 77.5%, 925/1,193). Among all women with CxCa, the overall rate of nondetection was 13.1% (212/1,615) for cotesting results (LBC negative/HPV negative) and this rate increased substantially when testing exceeded 12 months compared to within 1 year prediagnosis of either CxCa or precancer.ConclusionsAnalysis of 9-year cotest results from a national reference laboratory confirms the value of LBC element in cotesting. This supports that LBC/HPV cotesting enhances screening for the identification of CxCa in women 30 years and older, more so than LBC or HPV alone within cotesting.

Highlight 1. Discuss ASCCP guideline: CIN3 Risk is Reliable Surrogates for Invasive Cervical Cancer Risk 2. Discuss The Pittsburgh Cervical Cancer Screening Model

Background In the era of extensive data collection, there is a growing need for a large scale data analysis with tools that can handle many variables in one modeling framework. In this article, we present our recent applications of Bayesian network modeling to pathology informatics. Methods Bayesian networks (BNs) are probabilistic graphical models that represent domain knowledge and allow investigators to process this knowledge following sound rules of probability theory. BNs can be built based on expert opinion as well as learned from accumulating data sets. BN modeling is now recognized as a suitable approach for knowledge representation and reasoning under uncertainty. Over the last two decades BN have been successfully applied to many studies on medical prognosis and diagnosis. Results Based on data and expert knowledge, we have constructed several BN models to assess patient risk for subsequent specific histopathologic diagnoses and their related prognosis in gynecological cytopathology and breast pathology. These models include the Pittsburgh Cervical Cancer Screening Model assessing risk for histopathologic diagnoses of cervical precancer and cervical cancer, modeling of the significance of benign-appearing endometrial cells in Pap tests, diagnostic modeling to determine whether adenocarcinoma in tissue specimens is of endometrial or endocervical origin, and models to assess risk for recurrence of invasive breast carcinoma and ductal carcinoma in situ. Conclusions Bayesian network models can be used as powerful and flexible risk assessment tools on large clinical datasets and can quantitatively identify variables that are of greatest significance in predicting specific histopathologic diagnoses and their related prognosis. Resulting BN models are able to provide individualized quantitative risk assessments and prognostication for specific abnormal findings commonly reported in gynecological cytopathology and breast pathology.

Objective: The aim of this work was to raise awareness of problems using digital applications for examining, teaching, and applying telecytology at King Abdulaziz Medical City (KAMC), Riyadh, Saudi Arabia; University of Nebraska Medical Center (UNMC), Omaha, NE, USA; and University of Pittsburgh Medical Center (UPMC), Pittsburgh, PA, USA. The objective was to rationalize problems and propose alternative digital approaches. Study Design: We sought to identify solutions to improve the following: (a) interpretive examination scores at KAMC for complex cytological templates (i.e., high-grade squamous intraepithelial lesions [HSIL]) when using static digital images (SDI) of cells in regions of interest (ROI); (b) visualization of cells in 3D clusters when teaching at UNMC using 2D and 3D whole-slide imaging (WSI); and (c) visualization of cells through streaming telecytology at UPMC. Results: Composite SDI (CSDI) improved test scores for complex interpretations (i.e., HSIL) by converging diagnostic criteria from multiple ROI. Multiplane focusing through z-stacked WSI facilitated the teaching of cytological entities characterized by 3D cell clusters and consultative telecytology through robotic cell analysis. Conclusions: Adequately visualized cytomorphology and multiplane focusing are essential for virtual cytopathology examinations, teaching, or consultative telecytology. Visualization of diagnostic criteria through 2D or 3D imaging is critical. Panoptiq panoramic WSI with integrated z-stacked video clips enables optimal applied telecytology.

BACKGROUND Cervical cancer screening in China is largely limited to occasional opportunistic screening in urban centers. The current study reports histopathologic follow-up and human papillomavirus (HPV) results in women with high-grade squamous intraepithelial lesion (HSIL) Papanicolaou (Pap) tests reported at the largest academic women's hospital in China and compares these findings with those of published Western studies among frequently screened women. METHODS A retrospective cohort study documented HSIL Pap tests, patient age, HPV results, and histopathologic follow-up from 2011 through 2015 in the Obstetrics and Gynecology Hospital of Fudan University (OGHFU) in Shanghai, China. Of 886,122 Pap test results, 4269 (0.48%) reported HSIL. Histopathologic follow-up was available for 2351 cases and HPV results were available for 2092 cases. RESULTS HSIL reporting rates increased with patient age from 0.16% at age

Background: Cervical screening could potentially be improved by better stratifying individual risk for the development of cervical cancer or precancer, possibly even allowing follow-up of individual patients differently than proposed under current guidelines that focus primarily on recent screening test results. We explore the use of a Bayesian decision science model to quantitatively stratify individual risk for the development of cervical squamous neoplasia. Materials and Methods: We previously developed a dynamic multivariate Bayesian network model that uses cervical screening and histopathologic data collected over 13 years in our system to quantitatively estimate the risk of individuals for the development of cervical precancer or invasive cervical cancer. The database includes 1,126,048 liquid-based cytology test results belonging to 389,929 women. From-the-vial, high risk human papilloma virus (HPV) test results and follow-up gynecological surgical procedures were available on 33.6% and 12% of these results (378,896 and 134,727), respectively. Results: Historical data impacted 5-year cumulative risk for both histopathologic cervical intraepithelial neoplasia 3 (CIN3) and squamous cell carcinoma (SCC) diagnoses. The risk was highest in patients with prior high grade squamous intraepithelial lesion cytology results. Persistent abnormal cervical screening test results, either cytologic or HPV results, were associated with variable increasing risk for squamous neoplasia. Risk also increased with prior histopathologic diagnoses of precancer, including CIN2, CIN3, and adenocarcinoma in situ. Conclusions: Bayesian modeling allows for individualized quantitative risk assessments of system patients for histopathologic diagnoses of significant cervical squamous neoplasia, including very rare outcomes such as SCC.

Objectives In this study, we sought to correlate genotype test results for human papillomavirus (HPV) types 16, 18, and 45 with histopathologic follow-up diagnoses in patients with messenger RNA (mRNA) high-risk HPV-positive, cytology-negative results. Methods We identified 1,157 patients with mRNA HPV-positive, cytology-negative cervical screening test results between June 2015 and June 2018. Reflex HPV 16/18/45 genotype results were documented in 1,018 women aged 30 years or older, 318 of whom had follow-up within 18 months. Results Histopathologic findings of cervical intraepithelial neoplasia 2 or worse (CIN2+) were diagnosed in 14 of 122 (11.5%) patients positive for HPV 16/18/45 vs in seven of 196 (3.6%) HPV 16/18/45–negative patients. Three patients with high-risk HPV–positive, cytology-negative cervical screening test results were diagnosed with stage I cervical adenocarcinomas following early colposcopic referral and biopsy after HPV 16/18/45–positive genotype results. Conclusions Immediate reflex HPV 16/18/45 genotyping of mRNA HPV-positive, cytology-negative patients led to early colposcopic referral and histopathologic diagnoses of three difficult-to-detect, low-stage, cervical adenocarcinomas and significantly increased overall early detection of CIN2+ lesions.

Objectives: Abnormal signs or symptoms recorded on Papanicolaou (Pap) test requisitions may reflect disease not detected with Pap testing. Since 2009, these cases have been reviewed in our laboratory by a second cytotechnologist and a cytopathologist. The objective of this study was to document follow-up findings on these patients. Methods: A search for Pap test results of “Negative for intraepithelial lesion or malignancy, abnormal clinical signs or symptoms” was performed for cases from January 1, 2009, to October 10, 2013. Clinical information and follow-up findings were documented. Results: 1,104 cases were identified. Signs and symptoms were abnormal bleeding 897 (81%), polyps 83 (8%), pelvic mass 54 (5%), visible cervical lesions 48 (4%), vaginal lesions 17 (2%) and endometrial masses 6 (0.5%). Six hundred sixty-seven (60%) had follow-up results, including 517 with histopathologic diagnoses. Two-hundred thirty-three (45%) had nonspecific benign diagnoses, 216 (42%) had benign tumor-like conditions, 28 (4%) had insufficient specimens, 16 (3%) had precancerous diagnoses and 23 (4%) had malignancies. Endometrial malignancy was identified in 14 (61%), ovarian in 6 (26%), and miscellaneous in 3 (13%). No cervical cancers were identified. Conclusions: We report follow-up findings from patients with abnormal clinical signs or symptoms, negative Pap test results, and follow-up recommendations highlighting reported abnormal signs or symptoms. Abnormal clinical signs and symptoms should routinely be considered in assessment and management of patients with negative cervical screening test results.

Objectives: This study on human papillomavirus (HPV) testing in China’s largest independent laboratory accredited by the international Laboratory Accreditation Program of the College of American Pathologists extends previous reports on cervical screening test results from this Chinese facility. Methods: A retrospective laboratory database search from 2007 to 2014 documented high-risk HPV test results using either Hybrid Capture 2 (HC2; Qiagen, Hilden, Germany) or multiplex polymerase chain reaction fluorescence testing (MPFT) methods. Results: During the study period, HPV testing steadily increased, with 643,702 HC2 and 27,641 MPFT HPV tests performed. The mean ages of the tested women were 35.0 years using HC2 and 38.3 years using MPFT. The HC2 HPV-positive rate was 21.7%, significantly higher than 15.7% with MPFT ( P < .0001), with bimodal peak incidence in adolescents and women aged 60 to 69 years. Conclusions: Use of HPV testing in cervical screening is increasing in China. HC2 HPV-positive rates around 20% in all age groups from more than 500,000 tested Chinese women are consistent with previous reports from China and significantly higher than published HC2 HPV-positive rates in populations with more widespread cervical screening. MPFT HPV-positive rates were slightly lower in every age group. The high HPV-positive rate likely reflects limited routine cervical screening and high cervical cancer incidence in China.

Introduction Cervical cancer rates in China remain high, with only limited opportunistic screening in urban centers and large mostly unscreened rural areas. Cervical cytology practices in China have been changing over the last decade with introduction of The Bethesda System reporting terminology, liquid-based cytology (LBC), and programs for cervical cytology screening of underserved rural populations. An effort was undertaken for the first time to collect nationwide data on cervical cytology laboratory practices in China, a possible first step toward increased standardization and potential development of nationwide cytology quality benchmarks. Materials and methods Data on cervical cytology practices from 1572 laboratories operating in 26 nationwide Provisional Level Administrative Divisions was collected in an online survey approved through the Obstetrics and Gynecology Hospital of Fudan University in Shanghai. Results Over 90% of cervical cytology laboratories in China now solely use Bethesda System reporting terminology. LBC is now the most commonly utilized form of cervical cytology, with lower-cost Chinese-manufactured LBC formulations used in almost 70% of laboratories. Nationwide, significantly higher abnormal cytology rates were reported with LBC than with the conventional Papanicolaou smear (CPS); however, the CPS remains a useful low-cost alternative as China strives to extend cervical screening to large underserved rural areas. Conclusions Abnormal cytology rates were not significantly different when different levels of hospitals were compared. The survey identified nationwide opportunities for cytology quality improvement, including low rates of reporting of unsatisfactory cases and low rates for atypical glandular cells.

ObjectivesCervical screening strives to prevent cervical cancer (CxCa), minimizing morbidity and mortality. Most large US reports on cytology and human papillomavirus (HPV) cotesting of women aged 30 years and older are from one laboratory, which used conventional Papanicolaou (Pap) smears from 2003 to 2009.MethodsWe quantified detection of CxCa and precancer (cervical intraepithelial neoplasia 3/adenocarcinoma in situ [CIN3/AIS]) in 300,800 cotests at Magee Womens Hospital since 2005. Screening histories preceding CxCa and CIN3/AIS diagnoses were examined to assess the contribution of cytology and HPV testing. Cotesting utilized Food and Drug Administration-approved imaged liquid-based cytology (LBC) and from-the-vial HPV tests.ResultsLBC identified more women subsequently diagnosed with CxCa and CIN3/AIS than HPV testing. HPV-negative/cytology-positive results preceded 13.1% of CxCa and 7.2% of CIN3/AIS diagnoses.ConclusionsLBC enhanced cotesting detection of CxCa and CIN3/AIS to a greater extent than previously reported with conventional Pap smear and HPV cotesting.

Objective: To describe patient demographics, determine accuracy of clinical diagnosis, and evaluate reliability of laparoscopic uterine characteristics in the diagnosis of adenomyosis. Materials and Methods: Enrollment included 117 patients undergoing laparoscopic hysterectomy for benign indications. Intraoperatively, the attending surgeon predicted uterine weight; evaluated the presence of fibroids; and commented on the uterus' shape, color, and consistency while probing it with a blunt instrument. A prediction was also made about whether final pathology would reveal adenomyosis. Standardized video recordings were obtained at the start of the case. Each video was viewed retrospectively twice by three expert surgeons in a blinded fashion. Uterine characteristics were reported again with a prediction of whether or not there would be a pathologic diagnosis of adenomyosis. These data were used to calculate inter-and intrarater reliability of diagnosis. Results: Women with adenomyosis were more likely to complain of midline pain as opposed to lateral or diffuse pain (p = 0.048) with no difference in the timing of the pain (p = 0.404), compared to patients without adenomyosis. Uterine tenderness on examination was not an accurate predictor of adenomyosis (p = 0.566). Preoperative diagnosis of adenomyosis by clinicians was poor, with an accuracy rate of 51.7%. None of the intraoperative uterine characteristics were significant for predicting adenomyosis on final pathology, nor was any combination of the features (p = 0.546). Retrospective video reviews failed to reveal any uterine characteristics that generated consistent inter- or intrarater reliability (Krippendorff's α < 0.7) in making the diagnosis of adenomyosis. Conclusions: Clinical and video diagnosis of adenomyosis have low accuracy with no uterine characteristics consistently or reliably predicting adenomyosis on final pathology. (J GYNECOL SURG 34:183)

Objectives To study the human papillomavirus (HPV) genotype distribution of cervical cancer (CxCa) and cervical intraepithelial neoplasia grade 2/3 (CIN2/3) in China and to evaluate cotesting of HPV and cytology in CxCa screening. Methods Patients with histopathologic CxCa and CIN 2/3 diagnoses reported between January 2012 and June 2016 and extended HPV genotype testing in the prior 6 months were documented in the institute. Available prior Papanicolaou (Pap) test results were also documented. Extended HPV genotype testing was performed using two China Food and Drug Administration-approved HPV tests. Results CxCa and CIN 2/3 diagnoses and recent prior HPV test results were documented in 370 CxCa cases and 2774 CIN 2/3 cases. The high-risk (hr) HPV-positive rate was 88.4% for CxCa and 90.1% for CIN 2/3. Among 327 HPV-positive CxCa cases, the most common HPV types were HPV 16 (70.3%), 18 (7.0%), 58 (5.7%), 33 (4.1%), and 53 and 59 (1.9% each). Among 2499 hrHPV-positive CIN 2/3 cases, the most common HPV types were HPV 16 (53.3%), 58 (21.4%), 52 (11%), 33 (10.6%), and 18 (5.1%). 161 CxCa cases and 1094 CIN 2/3 cases also had available prior cotest results. Among cotested cases hrHPV-negative results were reported in 12.4% of CxCa and 10.1% of CIN 2/3 cases compared to cytology-negative results reported in 15.5% of CxCa and 4.3% of CIN 2/3. Conclusions HPV 16/18/59/39/45 genotypes were significantly more prevalent in CxCa cases than in CIN 2/3 cases, consistent with the more limited progressive potential of some CIN 2/3 lesions. Of CIN 2/3 and CxCa cases, 10% to 12% had recent negative hrHPV test results, pointing to a significant limitation of primary HPV screening.

Context Cervical cancer affects 12 000 women in the United States annually. However, despite its prevalence, there remains no good methodology to detect its recurrence. Objective To identify the role of cervicovaginal high-risk human papilloma virus (hr-HPV) testing in predicting cervical cancer recurrence. Design This is a retrospective study of patients who underwent hr-HPV testing as part of their routine surveillance for cervical cancer. Standard statistical analyses, including χ2 test and multivariable logistic regression, were performed with IBM SPSS 19.0. Results A total of 133 patients were identified, of whom 107 (80%) had squamous cell carcinoma. Ninety patients (68%) had bulky disease and were treated primarily with chemoradiation and brachytherapy. Of patients whose disease recurred, 5 patients (42%) had tested positive for hr-HPV during their surveillance period, compared to 13 patients (11%) for whom disease did not recur (relative risk: 3.88, P = .002). On multivariate logistic regression, hr-HPV status remained significantly predictive of disease recurrence (odds ratio: 12.3, P = .02, 95% confidence interval: 1.5–99.6). Using 2 × 2 table analysis, we found that while cervicovaginal cytology has limited specificity (5.7%) in predicting recurrence, the combination of cytology with hr-HPV testing increases the specificity of testing to 89.3%. Conclusions Persistence of hr-HPV is a risk factor for disease recurrence. High-risk–HPV testing is not routinely used during surveillance for cervical cancer, but this study suggests that large, prospective trials investigating the role of hr-HPV testing in cervical cancer surveillance are needed.

BACKGROUND In the United States, human papillomavirus (HPV) and Papanicolaou (Pap) testing (cotesting) for cervical screening in women ages 30 to 65 years is the preferred strategy, and cytology alone is acceptable. Recently, a proprietary automated test for identifying high-risk HPV types for primary cervical screening was approved by the US Food and Drug Administration. The objective of the current study was to document extensive cervical screening among these screening options. METHODS To investigate the sensitivity of various testing options for biopsy-proven cervical intraepithelial neoplasia grade 3 or worse (≥CIN3) and cancer, the authors reviewed 256,648 deidentified results from women ages 30 to 65 years at the time of cotest who had a cervical biopsy specimen obtained within 1 year of the cotest. RESULTS A positive cotest result was more sensitive (98.8%; 4040 of 4090 cotests) for diagnosing ≥CIN3 than either a positive HPV-only test (94%; 3845 of 4090 HPV-only tests) or a positive Pap-only test (91.3%; 3734 of 4090 Pap-only tests; P

Objectives: Cervical screening guidelines now recommend repeat cotesting of patients aged 30 years and older having a human papillomavirus (HPV)–negative low-grade squamous intraepithelial lesion (LSIL) in 1 year as preferred management. Only limited follow-up data on patients with HPV-negative LSILs are available from routine US clinical practice settings. Methods: In total, 680 patients with Hybrid Capture 2 (Qiagen, Hinden, Germany) high-risk HPV-negative LSIL ThinPrep (Hologic, Marlborough, MA) results were identified. Patients’ ages and histopathologic, cytologic, and HPV follow-up results were identified. Results: Among 680 patients with HPV-negative LSILs, 468 had follow-up within 1 year. During the study period, 14 (3.0%) of 468 had follow-up high-grade squamous intraepithelial lesion (HSIL) and 184 (39.3%) LSIL findings. No diagnoses of cervical carcinoma were documented. There were no significant follow-up differences between age groups. Of the 321 patients who had follow-up HPV testing, 271 (84.4%) had negative and 50 (15.6%) had positive HPV results. Conclusions: This is the largest study documenting follow-up results for patients with HPV-negative LSIL results based on prevalent US FDA–approved cotesting methods from one collection vial. These data document that risk for follow-up HSILs in these patients is low and also that no cervical cancers were diagnosed. These findings support recent recommendations for repeat cotesting after 1 year as an appropriate option for patients with HPV-negative LSIL results.

Objective: The Obstetrics and Gynecology Hospital of Fudan University (OGHFU) in Shanghai is the largest academic women's hospital in China. Between 2009 and 2014, the use of liquid-based cytology (LBC) significantly increased while gradually adopting the Bethesda System (TBS), and in 2012 local regulations mandated that pathologists replace technicians to sign out Pap tests. Design: A retrospective OGHFU database search documented all Pap test reports between 2009 and 2014 by specimen type, either LBC or conventional Pap smears (CPS), and final reporting category. A total of 1,224,785 Pap reports were analyzed to document variations in Pap test reporting during a period of major change in cervical screening in China. Results: LBC gradually replaced CPS, which declined from over 65% of Pap tests in 2010 to 6.4% in 2014. Of 514,811 Pap reports using the traditional class system, class I (negative) reports accounted for 98.3% of results. With the introduction of TBS reporting, pathologist reviews and substantial replacement of CPS by LBC, the laboratory abnormal Pap test rate increased significantly to almost 5%. Conclusions: Changes in cervical cytology reporting between 2009 and 2014 in China's largest academic women's hospital reflected both increased use of LBC and the introduction of pathologist TBS reporting. Abnormality rates increased significantly and fell within CAP benchmark ranges.