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Necrotizing funisitis is a distinct lesion of the umbilical cord associated with chorioamnionitis and bloodborne fetal infection. The lesion may be a response to microorganisms in Wharton's jelly. A common microorganism detected in chorioamnionitis is Ureaplasma urealyticum (U. urealyticum). This study hypothesizes that U. urealyticum DNA will be present in Wharton's jelly in necrotizing funisitis.Necrotizing funisitis was identified retrospectively from a 2-year pathology database and confirmed in review. Paraffin fixed embedded tissue sections of the lesion were prepared for polymerase chain reaction (PCR) by using primers to identify U. urealyticum. Twenty matched controls without funisitis were similarly processed. Clinical data included serological tests of common bloodborne infections in the mothers and infants, and U. urealyticum PCR results in the urine of the neonates.Fourteen cases of necrotizing funisitis were identified in 7,416 examined placentas. Nine of these umbilical cords were positive by PCR for U. urealyticum (64.3%). Nineteen of twenty control cases were negative. Eight of ten neonates (80%) also had positive urine PCR tests for U. urealyticum. No infants or mothers had evidence of bloodborne fetal infection.U. urealyticum DNA was present in Wharton's jelly by PCR testing in the majority of the necrotizing funisitis lesions tested. This result supports a possible causative role for U. urealyticum in many cases of necrotizing funisitis.

The value of extended high-risk human papillomavirus (hrHPV) genotyping for cervical cancer screening in women with low-grade squamous intraepithelial lesion (L-SIL) cytology has been recognized, but few studies have investigated this.Women with L-SIL Papanicolaou results who underwent human papillomavirus (HPV) genotyping between October 2017 and October 2021 at the Obstetrics and Gynecology Hospital of Fudan University were identified. Their HPV results were correlated with immediate histopathologic follow-up findings.In total, 8726 women who had L-SIL cytology and extended HPV genotyping results were analyzed. The overall hrHPV-positive rate was 84% in women with L-SIL, and the most prevalent hrHPV genotypes were type 52 (HPV52) (20.7%), HPV53 (15.7%), and HPV16 (14.3%). Single and multiple coinfections of hrHPV genotypes were detected in 57.2% and 42.8% of women with positive hrHPV results, respectively. Cervical intraepithelial neoplasia grade ≥2 (CIN2+) was identified in 8.5% of hrHPV-positive women. The CIN2+ detection rate in women who had multiple hrHPV infections (9.9%) was significantly higher than the rate in those who had infection with a single HPV type (7.2%). The top 5 CIN2+-associated HPV infections were HPV16 (25.2%), HPV82 (17.8%), HPV33 (16.3%), HPV31 (14.6%), and HPV26 (13.8%). For the composite group with HPV types HPV16, HPV26, HPV82, HPV31, HPV18, HPV33, HPV58, HPV35, HPV52, and HPV51, the risk of CIN2+ was 11.5% and represented 97.1% of all CIN2+ in biopsied, hrHPV-positive patients. The composite group of 8 remaining HPV genotypes (HPV39, HPV45, HPV53, HPV56, HPV59, HPV66, HPV68, and HPV73) was identified in 29.7% of hrHPV-positive patients, and the risk of CIN2+ for this composite group was similar to the risk of CIN2+ in hrHPV-negative patients.This large retrospective study in a predominantly unvaccinated cohort demonstrated that extended hrHPV genotyping improves genotype-specific risk stratification in women with L-SIL.

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.

Undifferentiated/dedifferentiated endometrial carcinomas (UDEC and DDEC) are rare, aggressive uterine neoplasms, with no specific line of differentiation. A significant proportion of these cases feature mutations of SWI/SNF chromatin remodeling complex members, including ARID1A, SMARCA4, and SMARCB1 genes. To study these entities more comprehensively, we identified 10 UDECs and 10 DDECs from our pathology archives, obtained clinicopathologic findings and follow-up data, and performed immunohistochemical studies for ARID1A, BRG1 (SMARCA4), and INI1 (SMARCB1) proteins. In addition, we successfully conducted targeted next-generation sequencing for 23 samples, including 7 UDECs, and 7 undifferentiated and 9 well/moderately-differentiated components of DDECs. Cases consisted of 18 hysterectomies and 2 curettage/biopsy specimens. Patient age ranged from 47 to 77 years (median, 59 years), with a median tumor size of 8.0 cm (range, 2.5-13.0 cm). All cases demonstrated lymphovascular invasion and the majority (13/20) were FIGO stage III-IV. By immunohistochemistry, ARID1A loss was observed in 15 cases, BRG1 loss in 4, and all cases had intact INI1 expression. A trend for enrichment of the undifferentiated component of DDECs for ARID1A loss was seen, although not statistically significant. Sequencing revealed frequent pathogenic mutations in PTEN, PIK3CA, ARID1A, CTNNB1, and RNF43, a recurrent MAX pathogenic mutation, and MYC and 12p copy number gains. In DDECs, the undifferentiated component featured a higher tumor mutational burden compared to the well/moderately-differentiated component; however, the mutational landscape largely overlapped. Overall, our study provides deep insights into the mutational landscape of UDEC/DDEC, SWI/SNF chromatin remodeling complex member status, and their potential relationships with tumor features.

Objective: In this prospective, population-based study, we evaluated the utility of high-risk human papillomavirus (HR-HPV) genotyping for triaging women with atypical squamous cells of undetermined significance (ASC-US) in the Chinese rural area. Methods: A total of 40,000 women were recruited from rural areas of Shanxi Province, China, between June 2014 and December 2014. Women with Pap results of ASC-US underwent HPV genotyping, colposcopy and histopathological examination. For those with normal cervixes or cervical intraepithelial neoplasia (CIN) 1 on the initial evaluation, a 2-year follow-up study was performed. Results: The reporting rate of ASC-US was 5.76% (2,304/40,000) in the study population. The detection rates of CIN 2 or above (CIN2+) and CIN 3 or above (CIN3+) in women with ASC-US were 7.28% and 1.75%, respectively. HPV 16 (39.53%), HPV 58 (17.83%), and HPV 52 (15.50%) were the three most prevalent HR-HPV genotypes among all women with ASC-US cytology. The five most common HR-HPV genotypes in CIN3+ lesions were HPV16, HPV58, HPV33, HPV31 and HPV18. Compared with the 15 HR-HPV testing, genotyping for a combination of HPV16/18/31/33/58 increased specificity significantly with virtually no loss of sensitivity for detecting CIN2+ and CIN3+ lesions, as well as significantly reduced colposcopy referral rate (23.15% vs 33.70%, p

Objectives SOX10 expression helps identify melanocytic lesions. Over time, novel uses have been identified, such as expression in triple-negative breast cancer (TNBC). We evaluated the usefulness of SOX10 in breast pathology—specifically, identification and subtyping of TNBC and distinction from gynecologic carcinomas, use as a myoepithelial marker, and in the distinction of usual ductal hyperplasia (UDH) from atypical ductal hyperplasia (ADH). Methods Several breast and gynecologic carcinoma tissue microarrays containing a total of 492 cases were stained with SOX10. Whole sections of 34 ADH, 50 UDH, and 29 ductal carcinoma in situ (DCIS) samples were also stained with SOX10. Results SOX10 expression was identified in 67% of consecutive TNBC cases. Expression was mostly seen in nonapocrine, androgen receptor (AR)–negative TNBCs. All gynecologic carcinomas (n = 157) were negative. All UDH cases showed mosaic SOX10 expression, while all ADH cases lacked expression. All estrogen receptor (ER)–positive DCIS (n = 19) specimens were negative for SOX10, while 2 of 10 ER-negative DCIS specimens were positive for SOX10. The latter 2 cases showed SOX10-positive invasive carcinomas. Conclusions SOX10 identifies nonluminal AR-type TNBC and is useful in distinguishing TNBC from gynecologic carcinomas. SOX10 can distinguish UDH from ADH. SOX10 is not useful in distinguishing ADH from DCIS.

OBJECTIVES The risks of adenocarcinoma in situ (AIS) recurrence or progression after conservative treatment are uncertain. The aim of this study was to examine the role of high-risk human papillomavirus (hrHPV) and cytology in the posttreatment surveillance of AIS patients. MATERIALS AND METHODS Follow-up results of hrHPV status, cytology results, and clinicopathological features of 207 patients were retrospectively analyzed, in whom AIS was initially treated by loop electrosurgical excision procedure (LEEP)/cone biopsy between September 2009 and June 2018. RESULTS Among 207 patients diagnosed AIS on LEEP/cone biopsy, 30.9% (64/207) had positive margins. Persistent/recurrent AIS rate was substantially higher in the patients with positive margins than in those with negative margins (47.2% vs 9.3%, p < .001). Of 74 patients with hrHPV surveillance, 17 (17/74, 23.0%) were found to have positive hrHPV and 4 (4/17, 23.5%) had the persistent/recurrent AIS regardless of margin status. On the contrast, no AIS were found in negative surveillant hrHPV patients (23.5% vs 0%, p < .001). Lastly, 27.8% patients (22/79) were reported atypical glandular cells on surveillant cytology, and 9 persistent/recurrent AIS cases were further identified on second biopsy or hysterectomy with a positive detection rate of 40.9%. CONCLUSIONS In this study, we concluded the positive margin on LEEP/cone biopsy in AIS patients was associated with a significantly greater risk of disease persistence or recurrence. The posttreatment surveillance by cytology and adjunct hrHPV would be an ideal strategy in predicting AIS persistence and recurrence, which will warrant further treatments.

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.

Primary cervical cancer screening by liquid-based cytology alone or with adjunctive HPV testing are available worldwide. However, little if any information is available about cervical cancer diagnostic yield of population-based cervical cancer screening in China. In response to it, we conducted a large prospective study on 40,000 women cervical cancer screening within six-month period in rural Shanxi Province, where has been reported as the highest cervical cancer rates in China. A standard cross-sectional survey by self-completed questionnaire was collected and followed by the liquid-based cytology screening. Follow-up biopsy with the diagnosis of cervical intraepithelial neoplasia 2 or higher lesion (CIN2+) were analyzed. Of initial 40,000 women participating in this study, 6.76% (2702/40,000) women had ASC-US or higher cytology screening results with ASC/SIL ratio at 6.14 (2381:388). Among them, 1.96% (782/40,000) women were found CIN lesions (95% CI, 1.68-2.23%) on confirmatory biopsies, including 0.55% (218/40,000) CIN2+ and 19 SCCa (47.5/100,000, 95% CI, 29-74/100,000). Women in Yangqu County had lower ASC/SIL ratio, but higher CIN2+ detection rate in comparison with that of Jiexiu County (6.69 vs. 8.84 and 56.7% vs. 43.9%), which reflects the cervical cancer distribution in different populations and regions. Analysis in age-stratified cytology results indicated women aged 60-65 years had the highest incidence of cytologic abnormality among all the age group; likewise, women aged >50 years were at higher risk in developing cervical high grade dysplasia or cancer than women aged

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.

Distinguishing between low-grade squamous intraepithelial lesions (LSIL) and high-grade squamous intraepithelial lesions (HSIL) can be difficult on certain Papanicolaou (Pap) tests, hindering interobserver concordance. We investigated the variables influencing the interpretation of LSIL versus HSIL in Pap test slides rejected from the College of American Pathologists PAP education program.Eleven cytologists, who were unaware of the reference interpretation, examined 21 Pap slides (11 submitted as LSIL and 10 as HSIL) rejected from the PAP education program and recorded the number of LSIL cells, HSIL cells, keratinized dysplastic cells, LSIL clusters with mixed HSIL cells, atypical squamous metaplasia, atypical glandular cells, the presence of inflammation or infectious organisms, and the overall interpretation (LSIL or HSIL). We evaluated the significance of these 11 variables using a nonlinear mixed model analysis.LSIL had greater concordance (92 of 121 responses; 76.0% concordance) than HSIL (68 of 110 responses; 61.8% concordance; P0.001). The only predictors of misclassified cases were the number of atypical squamous metaplastic cells and the number of HSIL cells (P0.001). The more of these cells identified, the more likely the reviewers were to classify the slide as HSIL. The reproducibility of the diagnosis was fair (Gwet's agreement coefficient, 0.33).Interobserver reproducibility is a challenge for a subset of cases with features intermediate between LSIL and HSIL. Atypical squamous metaplasia and dysplastic nuclei with a nuclear/cytoplasmic ratio greater than one half of the cell volume (HSIL) present on a Pap test influenced the likelihood that a reviewer would interpret the case as HSIL rather than LSIL.

Although folate status is associated with cervical carcinogenesis, it is not clear whether folate deficiency is associated with risk of cervical intraepithelial neoplasia (CIN) progression and infection with high-risk human-papillomavirus (hrHPV).To evaluate the associations of RBC and serum folate concentrations with prevalence of CIN grades and hrHPV infection, their interactions with prevalence of CIN grades, and RBC folate with the risk of CIN1 progressing to CIN2.Using data from the Shanxi CIN cohort of 2304 female Chinese adults, we used logistic-regression model to estimate ORs and prevalence ratios (PRs) of RBC and serum folate concentrations with prevalence of CIN grades and hrHPV infection. Categoric and spline analyses were used to evaluate the dose-response relations. We estimated the association of RBC folate with risk of CIN1 progressing to CIN2 in the nested case-control cohort.An inverse association was observed between increased RBC folate concentration and the odds of all CIN grades [quartile 1 (Q1) compared with Q4: OR: 2.28; 95% CI: 1.77, 2.93; Ptrend0.001]. Significant interaction of RBC folate and hrHPV infection was observed for prevalence of CIN2 or above (Pinteraction0.01). No associations were found between RBC and serum folate with PRs of hrHPV in each CIN grade. Over a median follow-up of 21.0 mo, RBC folate was associated with increased risk of CIN1 progressing to CIN2 (Q1 compared with Q4: OR: 3.86; 95% CI: 1.01, 14.76).Our study indicates that RBC folate concentration is associated with prevalence of CIN grades and CIN1 progression in female Chinese adults. Maintenance of normal folate status is important for reducing the risk of CIN and its progression in women with or without hrHPV infection.

BACKGROUND The objective of this study was to examine the prevalence of human papillomavirus 16/18 (HPV-16/18) genotypes and immediate histopathologic correlations in a Chinese population with negative cytology and positive high-risk human papillomavirus (hrHPV) testing. METHODS Patients who had documented negative cytology with immediate follow-up (within the 6 months after negative for intraepithelial lesion or malignancy Papanicolaou [Pap] testing), including a histopathologic examination and/or hrHPV testing, between 2011 and 2018 were included, and the data were analyzed. RESULTS Among 1,424,182 Pap tests, 1,333,453 (93.6%) were interpreted as negative cytology. Although conventional Pap smears had the highest reporting rate, cervical intraepithelial neoplasia 2 and higher (CIN-2+) lesions were detected significantly more with liquid-based cytology preparations (2.1%) than the conventional method (1.4%; P

Introduction Cervical cancer remains an important public health problem in Chinese women owing to the lack of a national screening program. The aim of the present study was to evaluate human papillomavirus (HPV) and Papanicolaou (Pap) test results preceding the histologic diagnosis of cervical intraepithelial neoplasia 2/3 (CIN2/3) in China’s largest College of American Pathologists-certified clinical laboratory. Materials and methods All cases of CIN2/3 histologically diagnosed from January 2011 to August 2016 were retrieved from the pathology department records. The Pap cytology and HPV test results from the 6 months before the CIN2/3 diagnoses were analyzed. Results A total of 5699 patients with histologically diagnosed CIN2/3 had previous Pap and/or HPV Hybrid Capture 2 testing results within the previous 6 months. The average age was 39.5 years (range, 16-82 years). Of these patients, 4288 had Pap test findings (average, 1.5 months) available. The results were high-grade squamous intraepithelial lesion in 44.1%, low-grade squamous intraepithelial lesion in 20.0%, atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion, in 16.0%, atypical squamous cells of undetermined significance, in 12.3%, atypical glandular cells in 0.7%, and negative in 6.9%. Of the 5699 patients, 2546 had HPV Hybrid Capture 2 test results (average, 1.4 months) available. Of these, 91.7% had positive results and 8.3% had negative results. Of 1135 patients with both previous Pap and HPV results, 7.1% had negative HPV results and 8.0% had negative Pap results (P = 0.38). Only 21 patients (1.9%) had double negative results. Conclusions The present study has reported the previous results of HPV testing and Pap cytology for patients with high-grade cervical squamous precursor lesions in a population of women in China who had not undergone intensive previous screening. Both high-risk HPV and Pap cytology had similar negative testing rates for these women, although double negative results were less common. These results support the value of combined testing in the detection of cervical cancer precursors.

Introduction We investigated the prevalence and carcinogenic risks of individual high-risk human papillomavirus (HR-HPV) in all types of cervical cytology specimens in the Shanghai population. Methods A total of 124,251 cases with cotesting of cytology and HPV genotyping between October 2017 and February 2020 were included. Results The overall HPV positive rate was 24.3%, with 22.9% for HR-HPV and 6.1% for low-risk HPV. The top five most common HR-HPV subtypes were HPV 52/16/58/53/39 in the entire studied population, and HPV 16/53/56/51/39 in women with abnormal cytology. The most prevalent subtypes in negative/LSIL, HSIL, and glandular lesions were HPV 52, 16, and 18, respectively. HPV 16, 33, 26, 18, 58, and 82 were the most common subtypes significantly associated with an increased risk for HSIL + cytology. HPV 16/18 were present in 53.6% and 66.7%, and HPV 16/18/31/33/45/52/58 were identified in 90.3% and 80.1% of HSIL and squamous cell carcinoma cytology, respectively. HPV 16/18 and HPV 16/18/31/33/45/52/58 were detected in 37.0% and 44.4% of women with cytologic interpretation of in situ and invasive adenocarcinoma. Conclusions This large-scale study identified the most common HPV subtypes in each cytology category, and the carcinogenic risks of individual HR-HPV in the studied Shanghai population. The results would provide valuable information for the development of next-generation HPV vaccines and cervical cancer screening programs for the Chinese population, and, more specifically, the Shanghai metropolitan population.

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.

Background Despite Aptima assay as the latest US Food Drug Administration (FDA)-approved high-risk human papillomavirus (hrHPV) test has been implemented as an adjunct in cervical cancer screening for years, histological follow-up data remain limited with respect to its performance in women with ASC-US Pap tests and positive hrHPV results. Methods Cases with results of ASC-US cytology and positive hrHPV by Aptima assay during the period 06/ 2015-02/2017 were retrieved from archived pathology reports. Immediate histological follow-up results were analyzed within 6 months interval after cotesting. Results Among 4196 women with ASC-US Pap tests and positive hrHPV, 51.1% of them had the immediate histological follow-up within 6 months. With positive Aptima hrHPV as the adjunct, 46.5% (95%CI 46.2-46.8) of ASC-US women were found to have cervical intraepithelial neoplasia type 1 (CIN1); 8.8% (95%CI 8.1-9.5) women were detected CIN2+ lesion including eight adenocarcinoma in-situ (AIS)s. CIN2+ detection rates were highest in women under 25 (15.4%, n = 65), when comparison with different age cutoffs, younger age women had higher CIN2+ lesion detection rate than that in older group (P Conclusion This is by far one of the largest retrospective studies to analyze the histological follow-up results of ASC-US women with positive hrHPV tested by Aptima hrHPV mRNA assay. The results indicated that younger women with ASC-US and positive hrHPV testing have highest risk of developing high grade CIN lesions as compared to the older women. Lastly, with positive HPV as the adjunct, 55.3% (1186/2145) of ASC-US women will result in the positive finding on histological follow-up.

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

Background The US American Society of Colposcopy and Cervical Pathology guidelines for cervical cancer screening have been largely adopted worldwide. Pooled high-risk human papillomavirus (hrHPV) testing has been routinely used to risk-stratify women who have atypical squamous cells of undetermined significance (ASC-US) cytology. However, it has been reported that there are distinguished differences in the distribution of hrHPV genotypes between the Chinese and American populations. Methods The objective of this study was to analyze the age-stratified reporting rates, hrHPV-positive rates, and genotyping by different cytology preparation methods and hrHPV testing assays, along with the immediate histopathologic correlation of ASC-US cytology, in the Chinese population. Results The ASC-US reporting rate of 1,597,136 Papanicolaou (Pap) tests was 4.2%, and the overall hrHPV-positive rate was 48.7% in the ASC-US cases. In total, 25,338 women with ASC-US Pap tests had immediate histologic follow-up, and the detection rate for cervical intraepithelial neoplasia 2 and higher lesions (CIN2+) was 7.1%, including 0.6% carcinomas. Among the women who underwent hrHPV testing, CIN2+ lesions were identified in 657 of 6154 (10.7%) who had hrHPV-positive results and in only 1.5% those who had hrHPV-negative results. Further genotyping analysis revealed that HPV types 16 and/or 18 were commonly identified genotypes among the Chinese women who had ASC-US cytology. Conclusions This large-scale study demonstrated that the hrHPV-positive rate, the CIN2+ detection rate, and the distribution of hrHPV genotypes in Chinese women with ASC-US cytology were essentially consistent with those from the American population, further supporting that the current and newly released 2019 American Society of Colposcopy and Cervical Pathology guidelines should be applicable to the Chinese population.

BACKGROUND Previous studies of the histologic correlation in women who have atypical squamous cells of undetermined significance cytology (ASC-US) and are positive for high-risk human papillomavirus (hrHPV+) have predominantly utilized the Hybrid Capture 2 (HC2) test, whereas the use of other US Food and Drug Administration (FDA)-approved methods is relatively limited. METHODS Cases of ASC-US/hrHPV+ that were tested using HC2, Cervista, or Aptima were retrieved, and the immediate histologic correlations were analyzed. RESULTS Overall, 53.9% (n = 3238) of women with ASC-US/hrHPV+ had immediate histologic correlation. The detection rates for grade 1 cervical intraepithelial neoplasia (CIN1) were similar among the 3 methods (37.1%-41.8%), while the overall detection rates for grade 2 CIN or higher (CIN2+) were much lower (5.1%-9.0%). CIN2+ detection rates were similar among different age groups for HC2 testing, whereas for Cervista and Aptima testing, detection rates were highest in the youngest group (age

Peritoneal washings (PW) can present frustrating dilemmas for the cytologist due to the prevalence, predominately in women, of benign proliferative processes of Mullerian, mesonephric, and mesothelial origin that may occur. In most instances, peritoneal washings or lavage are performed to screen for the presence of tumor cells in the peritoneal cavity and are performed in association with a surgical procedure. The goal of this assessment is not a primary cytologic diagnosis, but to confirm the presence or absence of tumor cells at that site, which makes comparison with the surgical specimen paramount. This chapter outlines an approach to these specimens, discusses commonly and uncommonly encountered entities along with their differential diagnoses and immunoprofiles, and provides numerous sample reports.

Context.—Reports for atypical squamous cells of undetermined significance (ASC-US) and histologic findings are rare in China.Objective.—To analyze the correlation findings of ASC-US cytology with high-risk human papillomavirus (hrHPV) test and histopathologic follow-ups.Design.—ASC-US cases with hrHPV test and histologic follow-ups between 2011 and 2015 were analyzed at a College of American Pathologists–certified laboratory.Results.—A total of 2 206 588 Papanicolaou (Pap) tests were performed, including 1 513 265 liquid-based cytology preparations (68.58%), and 693 323 conventional Pap tests (31.42%). The overall ASC-US reporting rate was 3.77% (83 199 of 2 206 588), with the highest in women aged 40 to 49 years. Of 18 574 women with ASC-US Pap and HPV testing, the hrHPV positivity rate was 34.98% (6498 of 18 574) with the highest in women younger than 30 years. A total of 6012 women with ASC-US Pap test findings had histologic follow-ups within 6 months; the overall cervical intraepithelial neoplasia 2 and above (CIN2+) detection rate was 7.87% (473 of 6012). One thousand nine hundred nine women with ASC-US Pap and HPV testing had histologic results. CIN2+ lesion was found in 13.98% (124 of 887) of women with ASC-US Pap/HPV-positive test results, significantly higher than 2.84% (29 of 1022) for women with ASC-US Pap/HPV-negative test results. Cervical squamous cell carcinoma was found in 3.95% (35 of 887) of women with ASC-US/HPV-positive test results.Conclusions.—This is one of the largest studies to investigate HPV and histologic follow-up findings in women with ASC-US in China. The ASC-US reporting rate, HPV positivity rate, and CIN2+ detection rate were all within the currently recognized benchmark ranges. These findings may contribute to establishing a baseline for better understanding of the status of cervical screening in China.

BACKGROUND Recent guidelines recommended the optional deferral of colposcopy for postmenopausal women with low-grade squamous intraepithelial lesion (LSIL) Papanicolaou (Pap) test results and negative human papillomavirus (HPV) testing. The objective of the current study was to assess the histopathologic follow-up of Cervista and Aptima high-risk HPV (hrHPV) testing in patients with LSIL cytology. METHODS Women with LSIL Pap test results and Cervista or Aptima hrHPV testing results were retrospectively identified from June 2013 through July 2017. Histological follow-up results within 6 months after LSIL Pap tests were analyzed. RESULTS A total of 1731 and 1906 cases of LSIL Pap tests, respectively, were tested on Cervista and Aptima platforms. Among the 2119 cases with histopathologic follow-up, cervical intraepithelial neoplasia of types 2/3 (CIN2/3) was diagnosed in 184 women (8.9%) and the detection rate was significantly higher in women with positive HPV testing compared with those with a negative result on both assays. Both methods demonstrated comparable performance for detecting CIN2/3 lesions. However, in women aged ≥50 years, the specificity for the detection of CIN2/3 lesions by the Aptima assay was statistically significantly higher than that of the Cervista test (48.7% vs 23.1%; P

Objective: The distribution of human papillomavirus (HPV) genotypes varies by countries and regions. Data regarding HPV genotype distribution for women with cervical intraepithelial neoplasia 2/3 (CIN2/3) are still limited. This study aimed to investigate the distribution of HPV genotypes for women with CIN2/3 in Shanxi province, China. Methods: Prior HPV testing/genotyping resulted from women with histologic diagnosis of CIN2/3 were retrospectively collected between August 2011 and August 2016. Results: A total of 1387 women with a diagnosis of CIN2/3 were included in this study. The average age of the women was 45.7 years and the average time period from HPV testing to histological diagnosis was 0.4 months. The overall high-risk HPV (hrHPV) positive rate was 91.6%. In all tested women, the most commonly detected hrHPV genotype was HPV16 (59.3%) followed by HPV58 (14.4%) and HPV33 (10.0%), while HPV18 was in the 6th position (6.0%). Conclusions: This is one of the largest studies of HPV genotyping for women with CIN2/3 in China. The prevalence and distribution of HPV genotypes in these Chinese women differed from those in women from Western countries. Our results provide important information for developing specific HPV vaccines for Chinese women.

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

Objectives Recently, three large Chinese cohort studies showed that 7.5% to 15.5% of patients with cervical carcinoma had negative high-risk human papillomavirus (hrHPV) test results on prior cytology specimens. These studies raise the question as to whether these negative hrHPV results represent truly hrHPV-negative carcinomas or false-negative hrHPV test results due to limitations in the testing of cytology specimens. This is increasingly an important question with increasing push to use hrHPV testing alone to screen for cervical cancer. Methods We investigated the hrHPV status on the surgical specimens from these same patients with cervical carcinoma using three polymerase chain reaction methods and a linear assay genotyping method. Results A variety of HPV genotypes were detected in 28 (45.9%) of 61 cases, all belonging to carcinogenic or possibly carcinogenic categories. HPV 16 was the most common genotype detected in positive cases (66.7%). HPV was detected in 25 (50%) of 50 squamous cell carcinomas and two (66.7%) of three adenosquamous carcinomas and only one (12.5%) of eight endocervical adenocarcinomas. Conclusions Our findings demonstrate that negative hrHPV testing on cervicovaginal cytology specimens in women later diagnosed with cervical carcinoma can be explained by the occurrence of truly HPV-negative carcinomas in more than half of patients. These results should be considered in the development of future cervical cancer screening guidelines.

We aimed to investigate the risk factors for cervical intraepithelial neoplasia (CIN) in Jiexiu, Shanxi Province, China. Twenty thousand eligible married women (age: 18-65 years) were administered with a questionnaire on potential risk factors for CIN and underwent liquid based Pap test. All women with abnormal cytological results underwent colposcopy with biopsy. Based on the biopsy pathology results, women were then assigned to either study group (with CIN) or control group (negative for histological results and volunteered to participate in the follow up study). The women in both study group and control group underwent vaginal microflora detection and dietary survey. The potential risk factors were analyzed by using ordinal logistic regression. Among the 20,000 women ne 1,438 women (7.19%) had cytologic abnormalities and 410 (2.05%) women were diagnosed histologically with CIN lesions, including 317 (1.58%) with CIN1, 93 (0.50%) with CIN2/3and 11 (55/100,000) with squamous cell carcinoma (SCC). The average daily dietary folate intake was significantly lower in the study group (344.61±153.07μg) than in the control group (371.50±166.58μg; P

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.