Genotype profile of HPV in ASC-H cytology and histologic follow-up-prevalence, distribution, and risk: A retrospective study of 1414 cases.

BACKGROUND: A cytologic diagnosis of atypical squamous cells, cannot exclude high-grade squamous lesion (ASC-H) poses a disproportionately high risk of cervical cancer development. The objective of this study was to analyze type-specific risks by mapping human papillomavirus (HPV) genotypes in ASC-H cytology. METHODS: In total, 1,048,581 Papanicolaou tests that had ASC-H cytology were retrieved. Concurrent HPV genotyping using proprietary multiplex real-time (MRT) and polymerase chain reaction (PCR) HPV tests and histologic follow-up findings were analyzed. RESULTS: Among 1678 patients who had ASC-H findings (0.16%), 1414 (84.3%) underwent concurrent HPV genotyping (MRT, 857; HPV PCR test, 557). The overall high-risk HPV (hrHPV)-positive rate was 84.4%. Of the 857 MRT cases, 63.9% were infected with a single hrHPV, and 24.4% had multiple genotypes. The most prevalent HPV types were HPV16/52/58/33/31. Lesions that were identified as cervical intraepithelial neoplasia 2 or worse (CIN2+) were detected in 498 of 906 cases (55.0%), including 81 cervical carcinomas (8.9%). The risk of CIN2+ for the composite group of HPV16/52/58/33/31-positive cases was 62.7%, representing 90.7% (264 of 291) of total CIN2+ lesions in ASC-H/hrHPV-positive cases by MRT. CIN2+ lesions were detected in 108 of 142 (76.1%) HPV16-positive and/or HPV18-positive women by the PCR the HPV test. Among 128 hrHPV-negative ASC-H cases by both methods, CIN2+ lesions were identified in 21 of 128 (16.4%), including five cervical carcinomas (3.9%). The sensitivity, specificity, positive predictive value, and negative predictive value for patients in the composite group with HPV16/52/58/33/31 were 88.0%, 40.8%, 62.7%, and 75.0%, respectively. CONCLUSIONS: Papanicolaou tests classified as ASC-H are associated with a high CIN2+ rate and warrant colposcopy, regardless of HPV status. The extent to which the risk-stratification provided by comprehensive HPV genotyping can inform the management of ASC-H cytology remains to be explored.

Comprehensive overview of genotype distribution and prevalence of human papillomavirus in cervical lesions.

Across cervical squamous and glandular lesions, a spectrum of human papillomavirus (HPV) genotypes has been identified. This review aims to provide a comprehensive summary detailing the distribution and profile of HPV genotypes detected in cervical lesions, leveraging insights from histological and cytological findings. High-risk HPV (HR-HPV) genotypes exhibit varying degrees of oncogenic potential, with HPV16 and HPV18 identified as the most prevalent and oncogenic types. The distribution of HR-HPV genotypes varies among different degrees of the cervical lesions and varies between squamous and glandular neoplasia. HPV16 is predominantly associated with severe lesions (precancers and carcinomas), while HPV18 demonstrates a significantly higher prevalence in endocervical as compared with squamous neoplasia. The distribution of HR-HPV in severe squamous lesions is complex, involving many HR-HPV genotypes in addition to HPV16, while the distribution of HR-HPV genotypes in endocervical glandular lesions is mainly limited in HPV18 and HPV16. Large datasets from China have identified the three most common HR-HPV genotypes in this population as stratified by diagnostic category: HPV52, HPV16, HPV58 in histologically negative cases and cervical intraepithelial neoplasia 1 (CIN1); HPV16, HPV52, HPV58 in CIN2/3; HPV16, HPV58, HPV52 or HPV18 in squamous cell carcinoma (SCC); HPV16, HPV18 and HPV52 in endocervical adenocarcinoma in situ (AIS), invasive adenocarcinoma, as well as mixed squamous and glandular lesions. HPV33 is the fourth most common HPV type in CIN2/3 and SCC, while HPV45 occurs more commonly in AIS and adenocarcinoma, compared with squamous lesions. The prevalence and distribution of multiple HR-HPV coinfections vary across different cervical diseases. The clinical significance and pathogenesis of these multiple HR-HPV infections remain uncertain, although recent two large studies demonstrate that multiple HR-HPV infections are not associated with cumulatively higher risk of high-grade cervical squamous lesion development, suggesting competitive and/or cooperative interactions among HPV genotypes. Extensive HPV genotyping aids in risk assessment and optimising clinical approaches for women with mild abnormalities in Pap cytology. Women with atypical squamous cells of undetermined significance (ASC-US) and low-grade squamous intraepithelial lesion (LSIL) Pap test results and with the infection of some HR-HPV genotypes carry a very low risk of high-grade cervical lesions. HPV genotyping can allow for risk stratification and triage optimisation for these HR-HPV-positive women. Women with atypical glandular cell (AGC) Pap test results showed a specific HPV genotyping pattern and extended HPV genotyping may be helpful for the clinical management of AGCs. Continual advancements in clinical guidelines integrating extended genotyping would increase diagnostic accuracy and refine strategies in clinical management.

Diagnostic significance and cytological features of NUT carcinoma by EBUS-FNA, a case report and literature review.

Cytomorphological features of NUT carcinoma include sheets or discrete nests of primitive, monotonous, round to oval shaped tumour cells with high N/C ratio and brisk mitotic figures. Abrupt squamous differentiation might be a diagnostic hint. More than 50% positivity of NUT immunohistochemistry staining is diagnostic. NUT carcinoma represents a poorly differentiated malignancy by extremely aggressive clinical course and poor prognosis. It frequently manifests in midline organs, notably in the mediastinum and lung. The rising preferences for utilizing the EBUS-FNA procedure in diagnosing thoracic and lung lesions stems from its high diagnostic yield. Hence, recognizing the cytomorphological features of NUT carcinoma is crucial for timely treatment and improved patient survival.

Associations of Single Versus Multiple Human Papillomavirus Infections With the Prevalence of Cervical Intraepithelial Neoplasia 2/3 and Squamous Cell Carcinoma Lesions: Human Papillomavirus Type-Specific Attribution.

The risk of developing cervical squamous lesions in women with multiple high-risk human papillomavirus (hrHPV) infections is uncertain. The aim of this retrospective study was to investigate the type-specific attribution and phylogenetic effects of single and multiple hrHPV subtypes in cervical squamous lesions. All cases with cervical histopathologic diagnosis and human papillomavirus (HPV) genotyping results in the 6 months preceding biopsy from October 2018 to December 2022 were studied and analyzed. Over the study period, 70,361 cases with histopathologic follow-up and prior HPV genotyping were identified. The hrHPV-positive rate was 55.6% (39,104/70,361), including single hrHPV detected in 27,182 (38.6%), 2 types of hrHPV detected in 8158 (11.6%), and 3 types of hrHPV detected in 2486 (3.5%). Among 16,457 cases with a histologically diagnosed squamous lesion (cervical intraepithelial neoplasia 1: 11411; cervical intraepithelial neoplasia 2/3: 4192; squamous cell carcinoma: 854 cases), the prevalence of single hrHPV infection increased, but the rate of multiple concomitant hrHPV infections showed negative association as the degree of squamous lesions increased. Among women with a single HPV16 infection, cervical intraepithelial neoplasia 2/3 and squamous cell carcinoma (CIN2+) diagnostic rate was 30.6%, and it increased to 47.6% when coinfected with HPV33 (P < .001) but significantly decreased when coinfected with all other hrHPV types (P < .05). By comparing CIN2+ diagnostic rates in 40 most common 2 types of hrHPV infections with related single hrHPV infection, CIN2+ rates were decreased in 12 combinations (30.0%), equivalent in 26 combinations (65.0%), and increased in 2 combinations (5.0%). The cases with 3 types of HPV infections reduced the risk for CIN2+ compared with related single HPV infections. HPV16+52+53, HPV16+52+68, HPV16+52+51, HPV16+39+52, and HPV16+58+53 significantly decreased the risk of CIN2+ compared with HPV16 single infection (P < .05). This study demonstrates that multiple hrHPV infections are not associated with cumulatively higher risk for CIN2+ development, suggesting that oncogenic progression of multiple hrHPV-associated cervical squamous lesions is neither synergistic nor a cumulative effect at the phylogenetic level, possibly a way of competitive interference.

Urinary Bladder "Melanosis": A Case Report and Review of the Literature.

Melanosis of the urinary bladder, so-called melanosis vesicae, is a rare condition characterized by dark, velvety bladder mucosa observed by cystoscopy examination. Up to 20 examples have been reported in the English literature, and the etiology of this disease still needs to be discovered. We present an 82-year-old woman with a history of pelvic organ prolapse-associated urinary symptoms. The patient was found to have pigmented urinary bladder mucosa on cystoscopy and underwent a total hysterectomy and bladder mucosal biopsy. Histologically, pigmented granules were evident in the bladder stroma and epithelium, highlighted by Periodic Acid-Schiff (PAS) stain, suggestive of lipofuscin in nature. We outline the diagnostic features of bladder melanosis, discuss the diagnostic mimickers, and thoroughly review the literature on the subject.

Single and Multiple High-Risk Human Papillomavirus Infections in Histopathologically Confirmed Cervical Squamous Lesions: Incidences, Distribution, and Associated Detection Rates for Precancerous and Cancerous Lesions.

Coinfection with multiple high-risk human papillomavirus (hrHPV) is frequently observed in cervical specimens; however, the clinical significance of concomitant multiple hrHPV infections is poorly understood, and the published results remain inconsistent. A retrospective study at a tertiary care institution was performed, evaluating Tellgenplex human papillomavirus (HPV) 27 genotyping or YanengBio HPV 23 genotyping results and immediate cervical histologic diagnosis (within 6 months after HPV genotyping), between November 2015 and October 2022. Among 49,299 cases with hrHPV genotyping and histologic diagnosis, 24,361 cases were diagnosed as cervical intraepithelial neoplasia (CIN) and squamous cell carcinoma. Among women with cervical squamous lesions, 86.5% (21,070/24,361) had hrHPV infections, and concomitant multiple hrHPV infections accounted for 24.7% of hrHPV-positive cases (5210/21,070). The hrHPV-positive rates in these cervical squamous lesions increased progressively with disease severity; however, the percentages of concomitant multiple hrHPV infection rates among hrHPV-positive cases decreased significantly with increasing degree of squamous abnormalities. There was no increased detection rate of CIN3+ (CIN3 and squamous cell carcinoma) in cases with concomitant 2 or 3 hrHPV genotype infections when compared with those with corresponding single hrHPV infections. Conversely, some combinations of multiple hrHPV infections demonstrated a decrease in the detection rates of CIN3+ lesions. In this large cohort, our results demonstrated that multiple hrHPV infections do not carry an increased risk for developing CIN3+ lesions when compared to the corresponding single-genotype infection. The reduced risk of CIN3+ in women infected with some combinations of hrHPV genotypes compared to those with single-genotype infections supports the concept of intergenotypic competition of hrHPV genotypes in cervical squamous lesions.

Updates in Cervical Cancer Screening Guidelines, The Bethesda System for Reporting Cervical Cytology, and Clinical Management Recommendations.

Over the past decades, cervical cancer has been a worldwide public health problem. Population-based early cancer risk detection and prevention approaches, including vaccination, cytology screening and human papilloma virus (HPV) detection, with the aligned clinical management, have formed a well-rounded high-quality implementation system for cervical cancer control, and revolutionarily improved the quality of life of women: (1) the success of cervical cancer screening practices, (2) standardization of The Bethesda system for reporting cervicovaginal cytology, (3) improvement in the understanding of HPV pathogenesis in cervical cancer, and (4) the development of appropriate management approaches have significantly decreased the disease burden of cervical cancer worldwide. This scoping review aimed to understand the evolvement of cervical cancer screening and management guidelines, describe the Bethesda cervical cytology reporting system, and HPV vaccines and tests, and highlight the key information of present policies and practices.

HER2 in uterine serous carcinoma: Current state and clinical perspectives.

OBJECTIVES: Uterine cancer has the highest incidence and the second-highest mortality rate among gynecologic malignancies in the United States. Although uterine serous carcinoma (USC) represents less than 10% of endometrial carcinomas, it accounts for a disproportionate 50% of tumor relapses and 40% of endometrial cancer deaths. Over the past decade, clinical trials have focused on finding better treatments for this aggressive subtype of endometrial cancer, especially HER2-targeted therapy. METHODS: We conducted a literature search in PubMed to expand the understanding of HER2 in USC. RESULTS: HER2 has been established as an important biomarker with prognostic and therapeutic implications in USC. Intratumoral heterogeneity and lateral/basolateral membranous staining of HER2 as well as high discordance between HER2 immunohistochemistry and in situ hybridization are more common in USC than in breast carcinoma. Therefore, a universal HER2 testing and scoring system more suitable to endometrial cancer is needed and currently under investigation. CONCLUSIONS: This review discusses the clinical perspective of HER2 overexpression/gene amplification in USC, the distinct HER2 staining pattern and the evaluation of HER2 in USC, the resistance mechanisms of HER2-targeted therapy in HER2-positive cancers, and likely areas of future investigation.

High-risk HPV testing improves accuracy in detection of CIN2+ lesions in ASC-H postmenopausal women? An academic hospital experiences.

Reflex human papilloma virus (HPV) testing with "atypical squamous cells, cannot exclude high-grade squamous lesion (ASC-H)" cytologic diagnosis is not recommended by American Society for Colposcopy and Cervical Pathology guidelines. Studies have shown human papillomavirus (HPV)-negative ASC-H patients of increased age are low risk for cervical intraepithelial neoplasia 2 or worse (CIN2+) lesions on colposcopic follow-up. We retrospectively assessed the efficacy of reflex HPV testing in postmenopausal women with ASC-H in the Los Angeles County hospitals and clinics in a 5-year period. Of a total 85 clinically postmenopausal women with ASC-H, 31 (36.5%) women were found to have CIN2+ lesions on follow-up biopsy and five of them were HPV-negative. Of the women with CIN2+ lesions and positive HPV, 13 (41.9%) were high-risk HPV (hrHPV) 16/18/45 positive and 13 (41.9%) were hrHPV-other subtype positive. Women with positive HPV had an over 3-fold increased risk of developing CIN2+ lesions (P = 0.008). Relative risk of hrHPV16/18/45 was 1.79-fold higher than that of hrHPV-other subtype. The positive predictive value and negative predictive value of hrHPV were 49.1% and 84.4%, respectively. CIN2+ detection rate in Hispanic women with positive hrHPV was higher than in non-Hispanic women (53.8% versus 35.7%). Overall, postmenopausal women with ASC-H cytology result and negative hrHPV were less likely to develop CIN2+ lesions, whereas about half of ASC-H postmenopausal women develop CIN2+ lesions if hrHPV positive, especially if hrHPV 16/18/45 positive. Therefore, triaging ASC-H postmenopausal women with cotesting or, ideally, hrHPV genotyping should be considered as optimal clinical practice to avoid overtreatment.

Performance of breast fine needle aspiration as an initial diagnostic tool: A large academic hospital experience.

BACKGROUND: The clinical performance of the Yokohama reporting system for breast cytology remains uncertain. METHODS: In this study, we retrospectively evaluated 318 breast fine needle aspirations (FNABs) from Los Angeles County Hospital over a five-year period, analysing data for breast cytology, histology, and radiology. RESULTS: Among 318 breast FNAB cases, 78.3% (249/318) were benign and 5.3% (17/318) malignant. Of 83 cases with follow-up histology, 14.5% (12/83) were insufficient, 66.3% (55/83) were benign, and 16.9% (17/83) were malignant. Of 55 benign cases, 61.8% (34/55) were fibroadenoma and 9 (9/55, 16.4%) were fibrocystic changes. Two cases were diagnosed as "atypical" but confirmed "benign" on core needle biopsy (CNB). No "suspicious" cases were found. Seventeen malignant cases were confirmed by CNB, including 70.6% (12/17) invasive ductal carcinoma, 11.8% (2/17) invasive lobular carcinoma, and one malignant phyllodes tumour. Receptor studies on cell blocks of three malignant cases showed concordant results with CNB results. In addition, 82.2% (148/180) of lesions with Breast Imaging-Reporting and Data System (BI-RADS) scores of 2 or 3 were benign and 92.3% (12/13) BI-RADS score 5 lesions were malignant on FNAB. Finally, 90% (67/74) of BI-RADS 4a lesions were benign, and 97% (36/37) of fibroadenomas were BI-RADS score 4a. CONCLUSION: This, by far the largest U.S. breast cytology study, showed 93.3% sensitivity, 100% specificity, 100% positive predictive value, and 98.2% negative predictive value for breast FNAB. Women with breast lesions of BI-RADS score 3 or less have a low risk of malignancy; FNAB would contribute to the reduction of excisional biopsies. FNAB can be considered as an initial diagnostic tool for BI-RADS 4 mass/lesions and satellite lesions, as well as for triaging patients.

Clinical-pathologic characteristics and response to neoadjuvant chemotherapy in triple-negative low Ki-67 proliferation (TNLP) breast cancers.

Triple-negative breast cancers (TNBCs) often have a high Ki-67 proliferation index and respond favorably to neoadjuvant chemotherapy (NACT) with pathologic complete response (pCR) resulting in ~40% of cases. Nevertheless, morbidity/mortality remain high, mostly due to recurrence in patients with residual disease. In contrast, the incidence and clinical features of TNBC with low proliferation (TNLP), defined as TNBC with a Ki-67 index of ≤30% remains unknown. We report 70 cases of TNLP identified at our center from 2008 to 2018, including 18 treated with NACT. TNLP tumors represent <1% of all breast cancers, and ~5-10% of TNBCs. Ninety percent of carcinomas were grade I/II and 70% were either pure apocrine or showed apocrine differentiation. Fifty cases had available immunohistochemistry results; 80%, 84%, 22%, and 20% were positive for AR, INPP4B, nestin, and SOX10, respectively. With a median follow-up of 72 months, 14% experienced recurrence, and 11% died of breast cancer. The tumor stage was prognostic. Among 39 stage-I patients, 18 (46%) received chemotherapy, but this did not impact survival. There was a trend for improved recurrence-free survival with chemotherapy in stage-II patients. Of the 18 patients treated with NACT, 2 (11%) showed pCR; these were notable for either high stromal TILs or a high mitotic count despite a low Ki-67 index. TNLPs are enriched in low to intermediate-grade carcinomas with apocrine features. Due to overall good prognosis of stage-I TNLP and the lack of clear benefit of chemotherapy, de-escalation of chemotherapy may be considered in select patients with stage-I TNLP.

Aptima HPV messenger RNA testing and histopathologic follow-up in women with HSIL cytology: A study emphasizing additional review of HPV-negative cases.

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 < .01). 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.

Borderline Brenner Tumor of the Ovary Coexisting With an Ovarian Mucinous Cystadenoma With Focal Atypical Epithelial Proliferation: A Rare Case With Review of the Literature.

Ovarian Brenner tumors, accounting for ∼5% of overall ovarian epithelial neoplasm, are often reported in association with mucinous neoplasm. Histogenetically, the two tumors are thought to arise from similar precursors. To date, fewer than 60 borderline Brenner tumors alone have been reported, and the concomitant presence of atypical proliferative components in Brenner and mucinous tumors is even rarer. Therefore, the clinicopathological characteristics and prognosis of patients with the borderline Brenner tumors alone or coexisting with mucinous neoplasm are extremely limited. Herein, we report a unique case of a 53-year-old woman with a unilateral ovarian borderline Brenner tumor associated with focal atypical mucinous epithelial proliferation and her clinical presentations. The clinicopathological features of the tumor are documented and the literature review along with the clinical molecular advances are summarized in this study.

Clinical performance of the aptima HPV assay in 4196 women with positive high-risk HPV and ASC-US cytology: A large women hospital experience.

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 <.01). 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.

Follow-up Findings in Postconservative Treatment Surveillance for Women With Cervical Adenocarcinoma In Situ.

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.

Determination of Methomyl Residue in Tobacco Samples by Heart-Cutting Two-Dimensional Liquid Chromatography with Tandem Mass Spectrometry.

A novel heart-cutting two-dimensional liquid chromatography coupled with tandem mass spectrometry (2D-LC-MS/MS) was developed for the qualitative and quantitative analysis of methomyl residue in tobacco. Compared to traditional methodologies, fairly high sensitivity and stability were achieved, and the sample procedure was simplified in the two-dimensional liquid chromatography (2D-LC) method. Although methomyl had poor retention performance in most of the reversed-phase liquid chromatography (RPLC) columns, an effective RP/RP strategy was successfully facilitated. An XB-Phenyl column was employed in the first dimension to effectively remove thousands of interference compounds in the matrix. In the second dimension, an ADME column was applied for further separation. After optimization of the separation conditions, a six-way valve was utilized for direct transformation of the target fraction from the 1st column to the 2nd column. A dynamic range of 2.5 ng/mL to 500 ng/mL was achieved with correlation coefficient (r 2) greater than 0.9995. The limit of detection and limit of quantification were determined to be 0.69 and 2.30 ng/mL, respectively. The 2D-LC method shows high sensitivity, good reproducibility, and recovery for methomyl in tobacco samples. Therefore, the new method was quite suitable for routine analysis.

Immediate histologic correlation in women with atypical squamous cells of undetermined significance cytology and positive high-risk HPV: A retrospective review of 6000 cases in a large academic women's hospital.

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 <25 years) and decreased with age. Statistical analyses revealed that the CIN2+ detection rate was significantly higher in younger women who were tested with Cervista. CONCLUSION: These hrHPV testing methods revealed low CIN2+ detection rates in women with ASC-US/hrHPV+ but demonstrated different patterns when using age-stratified analyses. The high rate of CIN2+ detection in women aged <25 years by the Cervista and Aptima testing platforms, but not the HC2 platform, suggest that continual investigation of FDA-approved clinical hrHPV testing-especially large-scale, long-term, prospective studies-is needed to evaluate the best options for management of ASC-US/hrHPV+ in this age group.

Encapsulation of vitamin D3 in gum arabic to enhance bioavailability and stability for beverage applications.

Delivery of vitamin D3 (VD3 ) in foods should exhibit desirable physicochemical characteristics and improves absorption. In this study, gum arabic (GA) was investigated as a VD3 carrier to encapsulate VD3 . VD3 dissolved in 5 mL ethanol corresponding to 0.3 to 6.0% mass of GA, was blended in 5.0% w/v GA solution, followed by freeze drying. The encapsulation efficiency decreased while loading capacity increased with an increased amount of VD3 . At the highest VD3 level, the loading capacity (3.47%) was the highest, and the encapsulation efficiency (61.24%) was satisfactory, and the treatment was further studied. The magnitude of negative zeta-potential increased from 3.1 to 31.0 mV at pH 2.0 to 7.4. During the 100-day storage at 3 °C of capsules reconstituted at pH 2.0 to 7.4, the hydrodynamic diameter decreased at all pH conditions, most evident for reduction to 81.3 nm at pH 7.4, and no precipitation was observed, indicating the significance of steric repulsion on capsule stability. Bioaccessibility of VD3 in capsules (95.76%) was significantly higher than the nonencapsulated VD3 (68.98%). The in vivo pharmacokinetic study in Sprague-Dawley rats after a single-dose of 300 µg VD3 showed the area-under-curve of serum 25(OHD) level in 48 hr of the encapsulation treatment was 4.32-fold of the nonencapsulated VD3 and more than twice higher than the VD3 -GA physical mixture. During 2-week supplementation of 60 µg VD3 /d, rats receiving capsules or physical mixture had 25(OH)D levels of at least 81 ng/mL higher than that of the nonencapsulated VD3 group. The studied encapsulation system holds great potential as a value-added ingredient to supplement VD3 in beverages with a wide pH range. PRACTICAL APPLICATION: The findings of this study demonstrated the improved dispersion stability and absorption of vitamin D3 after encapsulation in gum arabic. The capsules exhibited good dispersion stability across a pH range between 2.0 and 7.4, showing potential application in beverages. Furthermore, the enhanced absorption of VD3 after encapsulation highlights the nutritional benefits of the studied encapsulation system.

HPV detection rates and histopathologic follow-up of patients with HSIL cytology in a large academic women's hospital laboratory.

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.

Diagnostic Yield and Performance of a Large Population-Based Cervical Cancer Screening Program in High-Risk Rural China.

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 <50 years (0.82% vs. 0.49%). This large-scale cervical cancer screening study provided important references as the instructive for establishing the nation-wide cervical cancer screening strategy.