Neoplasia Grade Research Articles

Retrospective Cross-Sectional Epidemiological Study of Human Papillomavirus-Associated Precancers and Anogenital Warts in Patients Attending Specialized Clinics in Russian Federation

Background. In Russia, there are no country level registries on HPV-associated pre-cancers (cervical intraepithelial neoplasia, CIN; vulvar intraepithelial neoplasia, VIN; vaginal intraepithelial neoplasia, VaIN; anal intraepithelial neoplasia, AIN; penile intraepithelial neoplasia PIN) and anogenital warts (AWs) and no national-level cervical cancer screening program. Aims — the aim of this study was to assess the proportion of patients with CIN, VIN, VaIN, AIN, PIN and AWs diagnosis in the clinical settings in Russia. Methods. This study was a non-interventional retrospective multi-center chart-review study in 28 investigational sites representing 21 Federal subjects of 6 Federal Districts of Russia. Medical charts of adult men and women visited gynecology, sexual health, dermatovenerology or urology services between 1 Jan 2000 — 31 Dec 2019 were reviewed. Data were abstracted, using a standardized approach, on patient demographic characteristics, presence or absence of pre-cancers and AWs diagnoses, method of diagnosing pre-cancer and HPV infection, and grade of neoplasia. Results. A total of 11 520 patients (1732 male and 9788 female) were included in the analysis. The overall proportion of patients with HPV-associated precancers and AWs was 10.8%. By service type, cases of HPV-associated conditions were revealed most often in dermatological departments (14.5%) and gynecological hospitals (13.8%). CIN detection rate in Russian clinical settings increased over the 20-years from 3.2 to 11.1% and was higher in gynecological in-patient departments compared to out-patient departments (12.5 and 5.2% respectively). The number of non-cervical precancers (VIN, VaIN, AIN, PIN) cases were very low (the detection rate was less than 1%). The frequency of HPV type 16 and 18 detection increased from 0.6 to 4.8%, and from 0.2 to 1.9%, respectively, for the 20-years period. Conclusions. Our study suggested high level of HPV-related pre-cancer and AW disease burden as well as presence of high-risk HPV types. Preventive strategy through effective national HPV immunization program would be beneficial to reduce HPV-related disease burden in Russia.

Abstract 2208: Unexpected pattern in estimated prevalence of precancerous cervical lesions at a safety net hospital in Virginia: A case for epidemiologic surveillance

Abstract Objectives: High-grade squamous lesions of the cervix, (Cervical Intraepithelial Neoplasia (CIN) grade 2 and 3), are concerning, common, and costly precancerous findings, particularly for safety net hospitals who provide healthcare regardless of finances or insurance status. Epidemiologic surveillance of these lesions is uncommon but might be useful to guide preventive interventions. We sought to estimate the prevalence of CIN 2/3 and its racial and ethnic distribution, accounting for patient’s clinical and sociodemographic characteristics. Methods: We used data from hospital and physician billing claims for any CIN diagnosis occurring at the Virginia Commonwealth University Health System (VCUHS) from 01/01/2016 through 12/31/2020, along with respective clinical and sociodemographic characteristics at the time of diagnosis. We estimated average adjusted prevalence of CIN 2/3 lesions by race and ethnicity, from average marginal effects, after selecting most relevant patient factors from a logistic regression (LR) using backward selection (removing terms with p ≥ 0.2 and adding those with p < 0.1). Results: There were 1,538 women diagnosed with CIN 1, 2, 3, and unspecified dysplasia of the cervix uteri with respective prevalence of 45%, 14%, 12%, and 30%. CIN2/3 prevalence (26%) varied by race and ethnicity: Asians (39%) > Latinas (32%) > Whites (28%) >Blacks (23%) > Other (20%). Of the variables included in the LR model (age, marital status, religion, preferred language, insurance status, Body Mass Index, HIV, HPV, presence of bacterial vaginosis, hypertension, cholesterol, diabetes, pulmonary conditions, arthritis, heart conditions, pregnancy status, parity, smoking, alcohol, and previous cancer diagnoses), only age, diabetes, pulmonary conditions, smoking, and heart disease remained in the final LR model. The estimated average adjusted prevalence of a CIN 2/3 diagnosis remained highest for Asian women (35%, 95%CI: 17-52%), followed by Latinx (28%, 95%CI: 19-37%), Whites (25%, 95%CI 22-29%), Blacks (23%, 95%CI: 20-27%), and other (18%, 95%CI: 9-26%). Conclusions: The higher CIN 2/3 prevalence estimates among Asian women relative to other races and ethnicities is unexpected, as it does not align with current distribution of cervical cancer diagnoses at VCUHS (only 3% Asian), nor with the patterns of cervical cancer incidence and mortality rates in Virginia and in the United States, where Asian women have the lowest incidence and mortality. However, it potentially suggests a higher rate of regression, a finding supported by at least one surveillance study with similar findings. Citation Format: Shreya R. Raman, Stephanie A. Sullivan, Katherine Y. Tossas. Unexpected pattern in estimated prevalence of precancerous cervical lesions at a safety net hospital in Virginia: A case for epidemiologic surveillance [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2208.

Relationship between BMI, CT-derived body composition and colorectal neoplasia in a bowel screening population.

IntroductionObesity is associated with an increased risk of colorectal cancer (CRC). Unlike the indirect measures such as BMI, CT-Body composition (CT-BC) allows for the assessment of both volume and distribution of adipose tissue. Therefore, the aim of this study was to examine the relationship between host characteristics, BMI, CT-BC measurements and the incidence of colorectal neoplasia.MethodsPatients undergoing CT Colonography (CTC) as part of the Scottish Bowel Screening Programme, between July 2009 and February 2016, were eligible for inclusion. Data were collected including demographic data, clinicopathological variables and CT-BC measurements including skeletal muscle index (SMI), subcutaneous fat index (SFI) and visceral fat area (VFA). CTC, colonoscopy, and pathology reports were used to identify CRC incidence. Associations between demographic data, clinicopathological variables, CT-BC measurements, colorectal neoplasia and advanced colorectal neoplasia were analysed using univariate and multivariate binary logistics regression.Results286 patients met the inclusion criteria. Neoplasia was detected in 105 (37%) of the patients with advanced neoplasia being detected in 72 (69%) of patients. On multivariate analysis sex (p < 0.05) and high VFA (p < 0.001) remained independently associated with colorectal neoplasia. On multivariate analysis a high SFI (p < 0.01) remained independently associated with advanced colorectal neoplasia. BMI was not associated with either colorectal neoplasia or advanced colorectal neoplasia.ConclusionWhen directly compared to BMI, CT derived fat measurements were more closely associated with the degree of neoplasia in patients undergoing colorectal cancer screening. In patients investigated with CT colonography, CT adipose measures may stratify the risk and grade of neoplasia.

A127 ENDOSCOPIC MUCOSAL RESECTION FOR DYSPLASTIC AND NEOPLASTIC BARRETT’S ESOPHAGUS: FINDINGS FROM A FOREGUT NEOPLASIA MULTIDISCIPLINARY DATABASE

Abstract Background Previously, Barrett’s esophagus with high grade dysplasia (HGD) or neoplasia was treated with esophagectomy, which is associated with a high postoperative morbidity and mortality rate. Recent guidelines support the use of endoscopic mucosal resection (EMR) for T1a esophageal adenocarcinoma (EAC) and potentially T1b EAC; however, data on long term outcomes of endoscopic treatment is lacking. We created a combined prospective and retrospective multidisciplinary database to monitor outcomes of patients with Barrett’s esophagus undergoing endoscopic treatment. Aims Our primary aim was to compare outcomes of EMR and esophagectomy in patients presenting with BE and HGD, and/or early EAC. Methods A collaboration of gastroenterologists, general surgeons and thoracic surgeons from the University of Alberta, Edmonton, Alberta, provided input on the development of the database. All patients referred to the Northern Alberta Endoscopic Ablation Program from 2009–2021 who received at least one endoscopic treatment were included. A sub-analysis of all patients with pathologic confirmation of HGD, and/or early EAC was conducted to compare outcomes of EMR and esophagectomy. Results A total of 212 patients have been entered into the database. The most common findings were HGD, low grade dysplasia (LGD), and adenocarcinoma, respectively. All patients (n=48) who had at least LGD reached complete eradication of dysplasia (CE-D) and 95.8% reached complete eradication of intestinal metaplasia (CE-IM). Of those patients that reached CE-D, 8.3% developed recurrence of dysplasia (n=4). In the sub-analysis, 74 patients (76.3%) received endoscopic therapy while 23 patients (23.7%) received endoscopic therapy then ultimately an esophagectomy. There were significantly more T1b lesions in the esophagectomy group compared to the EMR group ( p&amp;lt;0.0001). Of all the patients in the EMR group, only 5.4% (n=4) had treatment related complications. Of patients receiving an esophagectomy, 60.9% (n=14) experienced treatment related complications. The mean length of stay for patients in the EMR group was 1.03 +/- 0.2 days, compared to 16.5 +/- 11.8 days for esophagectomy ( p&amp;lt;0.0001). Conclusions EMR provides definitive and durable treatment for BE lesions classified as T1b or less severe, with fewer complications and a shorter length of hospital stay than esophagectomy. Funding Agencies Alberta Innovates Health Solutions

Digital analysis of colposcopic images with acetowhite epithelium in "real-time" mode

Digital analysis is a method of assessing qualitative data by converting them into quantitative data using a personal computer’s graphics processing unit (GPU). Visual changes on the cervical surface in human papillomavirus (HPV)-associated pathology can be evaluated by extended colposcopy with a 3–5% acetic acid test and Schiller’s test. Acetowhite epithelium (appears after a test with acetic acid) in the form of flat condyloma is one of the main clinical manifestations of HPV infection (excluding manifestations on the metaplastic epithelium). The intensity of acetowhite epithelium (AWE) is a subjective parameter during gynecological examination, and to exclude the malignant process, a histology or liquid-based cytology should be performed. Objective assessment of the AWE intensity is introduced by digital image analysis using specialized software. The aim. To improve the assessment of visual changes of acetowhite epithelium on the cervical surface using a digital approach as an additional tool when performing extended colposcopy. Materials and methods. Colposcopy images of 359 patients were estimated by digital approach. Colposcopy images were made with a screenshot function after performing extended colposcopy. Screenshots of the cervix were converted to 8-bit type. This allowed us to estimate the intensity of AWE by software ImageJ. Index grey value (IndGV) was calculated to estimate the intensity of AWE. The IndGV data were assessed by MS office 365 (Excel v16.46) and RStudio v1.2.5042 statistical packages. Results and conclusion. The quantification approach detects the severity of AWE on the cervical surface. IndGV correlates with the grades of cervical intraepithelial neoplasia (CIN) and clinical manifestations of HPV. The clinical manifestations of HPV infection in CIN have a direct dependence on digital measurement as grey value (GV). These indicators give the opportunity to evaluate clinical manifestations in digital analysis in real-time mode, which does not require a significant financial investment. IndGV can be used as a prognostic factor of the severity of HPV infection and its clinical forms (CIN I–III and cervical cancer). Key words: digital medicine, quantitative approach, acetowhite epithelium, HPV infection

Significance of the viral load of high-risk HPV in the diagnosis and prediction of cervical lesions: a retrospective study

BackgroundThe significance of HPV viral load in the detection of cervical lesions is still controversial. This study analyzed the correlation between the high-risk HPV viral load and different cervical lesion degrees.MethodsThis retrospective study included women positive for high-risk HPV DNA and screened for cervical lesions between 01/2015 and 06/2018. The high-risk HPV DNA load was measured by the second-generation Hybrid Capture technology and classified as low, moderate, and high. Colposcopy and biopsy were performed in all patients. The patients were grouped as normal, cervical intraepithelial neoplasia (CIN) grade 1, CIN grade 2, CIN grade 3, and cervical cancer. Multivariable logistic regression was performed to explore the association between high-risk HPV DNA load and cervical lesions. The odds ratios (ORs) represent the odds for increasing from low to high viral load.ResultsFinally, 265 patients were grouped as normal (n = 125), CIN 1 (n = 51), CIN 2 (n = 23), CIN 3 (n = 46), and cervical cancer (n = 20). Among them, 139 (52.5%) had a low viral load, 90 (34.0) had a moderate viral load, and 36 (13.4%) had a high viral load. Taking the normal control group as a reference, a high viral load was an independent factor for CIN 1 (OR = 3.568, 95% CI: 1.164–10.941, P = 0.026), CIN 2 (OR = 6.939, 95% CI: 1.793–26.852, P = 0.005), CIN 3 (OR = 7.052, 95% CI: 2.304–21.586, P = 0.001), and cervical cancer (OR = 8.266, 95% CI: 2.120–32.233, P = 0.002).ConclusionsAmong women who underwent cervical biopsy, higher high-risk HPV viral load in cervical lesions was associated with a higher risk of high-grade cervical lesions.

Necessity for subsequent surgery in women of child-bearing age with positive margins after conization

Background20–25% of women with high-grade cervical intraepithelial neoplasias (HSIL) have residual lesions after conization. The state of the margin is generally considered to be a risk factor for recurrence or persistent lesions. Predictors of positive margins and residual lesions need to be identified. A design for postoperative management and avoidance of overtreatment needs to be provided, especially for women of child-bearing age.MethodsThis study was a retrospective analysis of 1309 women of child-bearing age with HSIL, who underwent cold knife conization (CKC). Age, gravidity, parity, human papillomavirus (HPV) species, cytology, transformation zone type, results of endocervical curettage (ECC), quadrant involvement, glandular involvement, and Cervical Intraepithelial Neoplasia (CIN) grade were analyzed. Among those with positive margins, 245 patients underwent secondary surgery within three months, including CKC, a loop electrosurgical excision procedure, and total hysterectomy. Risk factors for positive margins and residual lesions were assessed.ResultsThere was no significant difference in age, gravidity, parity, glandular involvement, and CIN grade between the two groups (P > 0.3). There was a significant difference in HPV species, cytology, ECC results, and quadrant involvement (P < 0.002). Multivariate analysis showed a major cytology abnormality, high-risk HPV infection, type III transformation zone, positive ECC result, and multiple quadrant involvement were independent risk factors for positive margins and residual lesions (P < 0.02). Age > 35 years was also a risk factor for residual lesions (P < 0.03).ConclusionHigh-risk women should be treated appropriately considering fertility. Patients with positive margins should be managed uniquely. Surgery for women without fertility may be appropriate. Close follow-up is necessary for women who have fertility requirements or are unwilling to undergo subsequent surgery if they have no risk factors, especially women < 35 years.

Current evidence on the adoption of indicator condition guided testing for HIV in western countries: A systematic review and meta-analysis.

BackgroundIndicator condition (IC) guided testing for HIV is an effective way to identify undiagnosed people living with HIV, but studies suggest its implementation is lacking. This systematic review provides an overview of the adoption of IC-guided testing in Western countries.MethodsSeven ICs were selected: tuberculosis (TB), malignant lymphoma, hepatitis B, hepatitis C, cervical/vulvar carcinoma/intraepithelial neoplasia grade 2+ (CC/CIN2+, VC/VIN2+), and peripheral neuropathy (PN). Embase and Ovid MEDLINE were searched up to November 20th, 2020. Publications of all types, using data from ≥2009, reporting on HIV test ratios in patients ≥18 years in all settings in Western countries were eligible. HIV test ratios and positivity were reported per IC. A random effects-model for proportions was used to calculate estimated proportions (ES) with 95% CIs. This study was registered at PROSPERO, registration number CRD42020160243.FindingsFifty-seven references, including 23 full-text articles and 34 other publications were included. Most (28/57) reported on HIV testing in TB. No reports on HIV testing in VC/VIN2+ or PN patients were eligible for inclusion. Large variation in HIV test ratios was observed between and within ICs, resulting from different testing approaches. Highest HIV test ratios (pooled ratio: 0·72, 95%CI 0·63–0·80) and positivity (0·05, 95% CI 0·03–0·06) were observed among TB patients, and lowest among CC/CIN2+ patients (pooled ES test ratio: 0·12, 95%CI 0·01–0·31, positivity: 0·00, 95%CI 0·00–0·00).InterpretationIC-guided HIV testing is insufficiently implemented in Western countries. The large variation in test ratios provides insight into priority areas for implementing routine IC-guided HIV testing in the future.FundingHIV Transmission Elimination in Amsterdam (H-TEAM) consortium and Aidsfonds (grant number P-42,702).

Multicentre Evaluation of Hepika Test Clinical Accuracy in Diagnosing HPV-Induced Cancer and Precancerous Lesions of the Uterine Cervix.

Objective: To evaluate the clinical accuracy of Hepika test to identify cancer/precancerous lesions of the uterine cervix. Materials and Methods: A multicentre retrospective study was carried out in 2018 and included 330 liquid-based cytology samples from three Italian centres of women aged 25–64 who had been tested for the human papillomavirus (HPV) and whose histology or follow-up outcome was known. Hepika is an enzyme-linked immunosorbent assay (ELISA) targeting the protein complexes E6#p53 and E7#pRb. After excluding samples without sufficient residual material, the clinical accuracy of Hepika test was evaluated in 274 samples: adenocarcinoma (ADC) (4), squamous cell carcinoma (SCC) (7), adenocarcinoma in situ (AIS) (1), cervical intraepithelial neoplasia (CIN) grade 3 (60), CIN2 (51), CIN1 (34), and negative histology (117). Association, sensitivity, and specificity for carcinoma, CIN3+ and CIN2+ are reported. Results: Positive Hepika test was associated with a high probability of carcinoma (odds ratio (DOR) = 33.68, 95% confidence interval (CI) 7.0–163.1); sensitivity was 81.8%, specificity, 88.2%. A positive Hepika test showed a weaker association with CIN3+ lesions (DOR = 3.5; 95% CI 1.75–6.99) and lower sensitivity (27.8%). Conclusion: The Hepika test was found to be an accurate biomarker for HPV-induced cervical carcinoma. Population-based prospective studies are needed to confirm the clinical usefulness of the Hepika test in the differential diagnosis of HPV-induced invasive lesions.

Evaluation and management of a pancreatic rest noted during pre-bariatric surgery screening endoscopy.

Pancreatic rest (PR) is an ectopic pancreatic lesion that is usually found incidentally on endoscopy or surgery. While most lesions do not have clinical significance, some patients are symptomatic and rarely, PR can predispose to malignancy. With the growing popularity of bariatric surgery, it has been unclear how to manage PR found on screening endoscopies, prior to bariatric surgery. Through review of the current literature, we propose an algorithm for clinicians to evaluate and manage PR found on screening endoscopies prior to bariatric surgery. We performed a literature search in PubMed pertaining to PR, clinical characteristics, risk of malignant transformation, endoscopic characteristics, histological descriptions, and resection techniques. Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), we found 33 published articles from 2001 to 2019, including case reports, case series, retrospective cohorts, and a review paper. PR is commonly found incidentally in the gastric antrum. Larger lesions have a higher risk of being symptomatic or predisposing to malignant transformation. Endoscopic ultrasound (EUS) can assist in the diagnosis of PR and guide resection technique. Certain histological characteristics, such as Heinrich class, grading of neoplasia, and genetic alterations, can determine malignancy risk of PR. Resection technique, either endoscopically or surgically, should be based on lesion size, depth of wall invasion, and the endoscopists' level of skill in endoscopic resection. Proper evaluation and treatment of PR should be considered because of the risk for symptoms and malignant transformation. Symptomatic lesions and those at risk for malignant transformation should be considered for resection. EUS can guide the diagnosis and type of resection, either endoscopically through EMR or ESD or surgically through sleeve gastrectomy or Roux-en-Y gastric bypass (RYGB).

Rate of detecting CIN3+ among patients with ASC-US using digital colposcopy and dynamic spectral imaging.

The present study compared two methods for the detection of severe cervical dysplasia in women with atypical squamous cells of underdetermined significance (ASC-US) cytology; digital colposcopy with adjunctive dynamic spectral imaging (DSI) and conventional colposcopy. IMPROVE-COLPO was a two-arm cross-sectional study of US community-based colposcopy. The active (prospective) arm of this study recruited patients examined by digital colposcopy and adjunctive DSI. Preceding consecutive patients that had been examined with conventional methods were used as historical controls in the retrospective arm of the study after being matched in number to those in the prospective arm by a colposcopist. In the present study, the primary measure was the number of women detected with cervical intraepithelial neoplasia (CIN) grade 3 or worse (CIN3+) following punch biopsy. The study included 1,353 retrospective and 1,226 prospective patients eligible for this analysis who were examined by 146 colposcopists in 42 community-based clinics. The patient baseline characteristics were comparable between the two arms. The average number of biopsies taken per patient was higher among the prospective arm patients (including standard and DSI-assisted biopsies) compared with the retrospective arm control patients (1.21 vs. 0.97 respectively). Biopsy detected 31 patients with CIN3+ [2.29%; 95% confidence interval (CI), 1.56-3.24] in the retrospective arm, and 48 patients with CIN3+ (3.92%; 95% CI, 2.90-5.16) in the prospective arm. The difference in the number of patients detected with CIN3+ in the two arms of the study was 1.62% (95% CI, 0.30-3.04; P=0.022), which corresponds to a 70.9% relative increase in the prospective compared with the retrospective arm. Biopsy appeared less efficient in detecting patients with CIN3+ in the retrospective arm compared with the prospective arm. However, there was no statistically significant difference between the retrospective arm and the prospective arm in terms of: i) Biopsies taken (over the entire population) per patient detected with CIN3+ (42.2 in the retrospective arm vs. 30.8 in the prospective arm; P=0.164) and ii) positive predictive value of using biopsies to identify patients with CIN3+ (2.83 vs. 3.92; P=0.118). Adoption of digital colposcopy with DSI increased the number of biopsies collected from ASC-US patients compared with retrospective controls of standard colposcopy and detected a significantly higher number of patients who were CIN3+. The number of additional biopsies taken in the prospective arm compared with the retrospective arm was too small to explain the increased detection of patients with CIN3+ observed in the prospective arm, suggesting that biopsies in the prospective arm were better at identifying CIN3+.

Regulation of LCoR and RIP140 expression in cervical intraepithelial neoplasia and correlation with CIN progression and dedifferentiation

PurposeLigand-dependent corepressor (LCoR) and receptor-interacting protein 140 (RIP140/NRIP1) play an important role in the regulation of multiple oncogenic signaling pathways and the development of cancer. LCoR and RIP140 form a nuclear complex in breast cancer cells and are of prognostic value in further prostate and cervical cancer. The purpose of this study was to analyze the regulation of these proteins in the development of cervical intraepithelial neoplasia (CIN I–III).MethodsImmunohistochemical analysis was obtained to quantify RIP140 and LCoR expression in formalin-fixed paraffin embedded tissue sections of cervical intraepithelial neoplasia samples. Tissue (n = 94) was collected from patients treated in the Department of Gynecology and Obstetrics, Ludwig-Maximilians-University of Munich, Germany, between 2002 and 2014. Correlations of expression levels with clinical outcome were carried out to assess for prognostic relevance in patients with CIN2 progression. Kruskal–Wallis test and Mann–Whitney U test were used for data analysis.ResultsNuclear LCoR overexpression correlates significantly with CIN II progression. Nuclear RIP140 expression significantly increases and nuclear LCoR expression decreases with higher grading of cervical intraepithelial neoplasia. Cytoplasmic RIP140 expression is significantly higher in CIN III than in CIN I or CIN II.ConclusionA decrease of nuclear LCoR expression in line with an increase of dedifferentiation of CIN can be observed. Nuclear LCoR overexpression correlates with CIN II progression indicating a prognostic value of LCoR in cervical intraepithelial neoplasia. Nuclear and cytoplasmic RIP140 expression increases significantly with higher grading of cervical intraepithelial neoplasia underlining its potential role in the development of pre-cancerous lesions. These findings support the relevance of LCoR and RIP140 in the tumorigenesis indicating a possible role of LCoR and RIP140 as targets for novel therapeutic approaches in cervical intraepithelial neoplasia and cervical cancer.

Differential expression of human papillomavirus 16-, 18-, 52-, and 58-derived transcripts in cervical intraepithelial neoplasia

BackgroundHuman papillomavirus (HPV) infection is a primary cause of cervical cancer. Although epidemiologic study revealed that carcinogenic risk differs according to HPV genotypes, the expression patterns of HPV-derived transcripts and their dependence on HPV genotypes have not yet been fully elucidated.MethodsIn this study, 382 patients with abnormal cervical cytology were enrolled to assess the associations between HPV-derived transcripts and cervical intraepithelial neoplasia (CIN) grades and/or HPV genotypes. Specifically, four HPV-derived transcripts, namely, oncogenes E6 and E6*, E1^E4, and viral capsid protein L1 in four major HPV genotypes—HPV 16, 18, 52, and 58—were investigated.ResultsThe detection rate of E6/E6* increased with CIN progression, whereas there was no significant change in the detection rate of E1^E4 or L1 among CIN grades. In addition, we found that L1 gene expression was HPV type-dependent. Almost all HPV 52-positive specimens, approximately 50% of HPV 58-positive specimens, around 33% of HPV 16-positive specimens, and only one HPV18-positive specimen expressed L1.ConclusionsWe demonstrated that HPV-derived transcripts are HPV genotype-dependent. Especially, expression patterns of L1 gene expression might reflect HPV genotype-dependent patterns of carcinogenesis.

A Comparative Study between Conventional Pap Smear and Liquid-Based Cytology: A Clinco-Cytological Study of Iraqi Women with Some Health Problems of Cervix

A cervical screening by Pap test is necessary in recognizing precancerous and cancerous cases to reduce mortality due to cervical cancer among women. Regular screening and follow up can make it easier to early diagnose and eventually, to treat and control cervical cancer.&#x0D; This study aimed to detect atypical pathological changes of the vagina and uterine cervix of a sample of Iraqi women by macro- and micro-examination, and to determine the link with the demographic features. Also the study aimed to evaluate the two Pap smear techniques; the conventional and the base liquid methods.&#x0D; The study included 50 women with genital health problems (18-50 years old) who were referred to the National Cancer Research Center (NCRC), the University of Baghdad, during the period from 1st April to 30st of September 2018. Both visual inspection of the uterine cervix and Papanicolaou smear were performed for all of the participants.&#x0D; The results showed that most patient women (96%) were married and sexually active, with 51% being married under 20 years of age .Visual inspection of the cervix showed that 30% of the women had translucent, opaque or erosion lesions. Upon cytology examination, 92% of the women showed nonspecific inflammation, 70% revealed reactive squamous metaplasia, 10% had Koilocytotic atypia, and 8% suffered from cervical intraepithelial neoplasia (CIN1) or low grade squamous intraepithelial lesion (LGSIL). Contraception was used by 82% of the patients, while 36% used pills. The causes of the referral to the centre were abnormal vaginal discharge (44%) and post-coital bleeding "and\or" dyspareunia (20% each). Lastly, 74% of the participants did not make this test previously. Liquid-based cytology technique outperformed conventional pap smears because of improved fixation, decreased impurities factors, and standardization of cell transfer.&#x0D; We conclude that routine screening and Pap smear testing for uterine cervix and vagina might be useful to prevent the occurrence of precancerous lesions in the genital system of sexually active women. We recommend to apply this test before and after treatment and to activate the cellular examination in the basal fluid method

Clinical significance of human papillomavirus 16/18 E6 protein detection in shunting and prognosis of patients with atypical squamous cells of undetermined significance and low-grade squamous intraepithelial lesions

Objective To evaluate the value of human papillomavirus (HPV) 16/18 E6 protein detection in shunting and prognosis in patients with atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesions (LSIL). Methods A total of 98 patients with ASCUS or LSIL from the Affiliated Cancer Hospital of Shanxi Medical University between May 2014 and May 2015 were selected as the subjects. All of them received the thin-cytologic test (TCT), HPV DNA, HPV16/18 E6 protein tests and colposcopy examination. After 3-year follow-up of patients with cervical intraepithelial neoplasia (CIN) grade Ⅰor bellow lesions diagnosed by biopsy and 30 negative controls, the above tests were performed again. The efficacies of all the tests were analyzed. The value of CIN grade Ⅱ or above was predicted. Results The sensitivity, specificity, positive predictive value and negative predictive value in predicting CIN grade Ⅱ or above lesions of HPV16/18 E6 protein, HPV DNA and HPV16/18 DNA was 30.8%, 95.3%, 50.0%, 90.0%, respectively; 84.6%, 37.6%, 17.2%, 94.1%, respectively and 61.5%, 67.1%, 22.2%, 91.9%, respectively in shunting study. The relative risk (RR) of CIN grade Ⅱor above lesions in patients with positive HPV16/18 E6 protein, persistent positive HPV16/18 DNA and positive HPV16/18 DNA was 13.429, 10.231 and 8.343, respectively in the follow-up study. Odds ratio (OR) of HPV16/18 E6 positive protein presenting persistent positive HPV16/18 DNA was 34.833 (95% CI 5.020-241.711). Conclusions In patients with ASCUS and LSIL, the specificity and positive predictive value of HPV16/18 E6 protein in predicting CIN grade Ⅱ or above lesions are higher than those of HPV DNA and HPV16/18 DNA. Moreover, these patients with HPV16/18 E6 protein positive have a higher risk of developing CIN grade Ⅱ or above lesions and persistent positive HPV16/18 DNA. Key words: Atypical squamous cells of undetermined significance; Low-grade squamous intraepithelial lesions; Human papillomavirus 16; Human papillomavirus 18; E6 protein

Over Expressed TKTL1, CIP-2A, and B-MYB Proteins in Uterine Cervix Epithelium Scrapings as Potential Risk Predictive Biomarkers in HR-HPV-Infected LSIL/ASCUS Patients.

High oncogenic risk human papillomaviruses (HR-HPVs) promote cervical carcinoma development, the fourth most common feminine cancer. A slow oncodevelopmental phase—defined histopathologically as Cervical Intraepithelial Neoplasia (CIN) grades 1–3, or cytologically as Low- or High-grade Squamous Intraepithelial Lesions (LSIL or HSIL)—precedes the malignancy. Cervical carcinoma screenings through HR-HPV genotyping and Pap smears are regularly performed in Western countries. Faulty cytology screening or genotyping or patients' non-compliance with follow-ups can let slip an oncoprogression diagnosis. Novel biomarker tests flanking HR-HPV genotyping and cytology could objectively predict the risk of disease progression thus helping triage LSIL/ASCUS patients. Here, anonymized leftovers of fresh cervical epithelium scrapings from twice (LSIL/ASCUS and HR-HPV DNA)-positive and twice (Pap smear- and HR-HPV DNA)-negative (control) patients in a proteome-preserving solution served to assess the biomarker worth of three cervical carcinoma-related proteins, i.e., B-MYB (or MYBL2), Cancerous Inhibitor of PP2A (CIP-2a), and transketolase-like1 (TKTL1). Leftovers anonymity was strictly kept and storage at −80°C, protein extraction, immunoblotting, and band densitometry were blindly performed. Only after tests completion, the anonymous yet code-corresponding HR-HPV-genotyping and cytology data allowed to assign each sample to the twice-positive or twice-negative group. Descriptive statistics showed that the three proteins levels significantly increased in the twice-positive vs. twice-negative scrapings. Diagnostic ROC curve analysis identified each protein's Optimal Decision Threshold (OTD) showing that TKTL1 and CIP-2a are stronger risk predictive biomarkers (Sensitivity, 0.91–0.93; Specificity, 0.77–0.83) than B-MYB. Logistic Regression coupled with Likelihood-Ratio Tests confirmed that a highly significant relation links increasing TKTL1/CIP-2a/B-MYB protein levels in twice-positive cervical scrapings to the risk of HR-HPV-driven oncoprogression. Finally, a 3 year clinical follow-up showed that 13 patients (50% of total) of the twice-positive group with biomarker values over OTDs compliantly underwent scheduled colposcopy and biopsy. Of these, 11 (i.e., 84.7%) received a positive histological diagnosis, i.e., CIN1 (n = 5; 38.5%) or CIN2/CIN2+ (n = 6; 46,2%). Therefore, TKTL1/CIP-2a/B-MYB protein levels could objectively predict oncoprogression risk in twice (HR-HPV- and Pap smear)-positive women. Further studies will assess the translatability of these findings into clinical settings.

Prevalence of human papillomavirus and subtype distribution in male partners of women with cervical intraepithelial neoplasia (CIN): a systematic review

BackgroundHuman Papillomavirus (HPV) infection is estimated to be the most common sexually transmitted infection. The present systematic review summarizes data regarding the prevalence of HPV and the distribution of subtypes in heterosexual male partners of women, who were diagnosed with any grade of cervical intraepithelial neoplasia (CIN).MethodsWe conducted a systematic review of the literature by Medline and Google Scholar databases using the terms “Human Papillomavirus” or “HPV” plus “men” or “male partners” or “women with CIN”. We included original published English-language articles published from 1/1/2000 until 1/1/2018 that had screened male partners of women with CIN using HPV DNA testing. We excluded studies that they overlapped with other included studies or were unrelated to the study subject.ResultsWe included a total of 12 publications, which reported the prevalence of HPV in free-clinical signs male partners of women with CIN. The largest proportion of the studies were from South America (seven studies), and the rest from Europe. The mean age of participants was 35.18 + − 3.47 years. HPV prevalence ranged from 12.9 to 86%; the total HPV prevalence among the studies was 49.1%, while ten out twelve studies (83.3%) demonstrated prevalence > 20%. Between the studies, the distribution of HPV subtypes varied on the basis of the method used, on the population and on the geographic region. A great variety of subtypes were detected, including 6, 11, 16, 18, 31, 33, 40, 42, 45, 51, 52, 53, 54, 56, 57, 58, 59, 61, 62, 66, 68, 81 and 83. In six studies the HPV 16 was the most frequent, while in two others the HPV 6 and HPV 83.ConclusionsUntil now, there are not precise screening or surveillance guidelines for the management of partners of women with CIN. This population is frequently colonized by various HPV subtypes and therefore need to be screened in an effort to reduce the infection in both sexes. The screening test could include detection/identification of HPV subtypes by a molecular assay, followed by peniscopy only in the positive cases.

Cervical Intra-Epithelial Neoplasia: Index of Papillomavirus Infection and Histopathological Grade in Lubumbashi Patients

The aim of this study is to show the relationship between the index of Papillomavirus infection and the grade of cervical intraepithelial neoplasia as proposed by WHO in Lubumbashi patients. This is a cross-sectional analytical study on cervical biopsies whose histological diagnosis is an intraepithelial neoplasia registered in two Laboratory of Patholoy in Lubumbashi for a period of two years from June 2017 to June 2019. The following results were observed: A total of 41 cases of intraepithelial neoplasia were recorded out of 91 cervical biopsies is 43.2%. Five indices of Human Papillomavirus infection are found in Lubumbashi patients in variable proportions without statistically significant difference; that is the index (5) in 29.27%, the indices (7) and (9) in 21.95% for each index, the index (6) in 17.07% and the index (8) in 9.76%. The three grades of intraepithelial neoplasia proposed by the WHO since 2003 are also found in Lubumbashi patients in varying proportions with no statistically significant difference; 48.78% for grade 3; 36.59% for grade 2 and 14.63% for grade 1. There is no relationship between the HPV infection index and the grade of cervical intraepithelial neoplasia; calculated linear correlation r ^ 2 is equal to 0.00.

Comparison of cervical cancer screening among women with and without hysterectomies: a nationwide population-based study in Korea

BackgroundCervical cancer screening is not recommended for women who underwent hysterectomy with no history of cervical intraepithelial neoplasia (CIN) of grade 2 or higher. We aimed to determine the cervical cancer screening rate in Korean women who underwent hysterectomies and compare it to that in women with intact uteri.MethodsWe used data from the 2014–2016 Korean National Cancer Screening Survey; 6807 women aged 30–74 years were included in the study. Participants were asked about their experiences with cervical cancer screening, hysterectomy status, and other variables associated with cancer screening.ResultsThe screening rates among women who have undergone a hysterectomy vs. those who have not during the past 2 years were 61.8% (95% confidence interval [CI], 58.8–64.9) and 64.7% (95% CI, 64.1–65.3), respectively. Among younger women (30–44 years) and women with a family history of cancer, those with hysterectomies showed a higher cervical cancer screening rate than those without (77.8% vs. 57.1% and 75.0% vs. 67.1%, respectively).ConclusionsDespite available evidence and clinical recommendations, a considerable number of Korean women who no longer have a cervix continue to undergo unnecessary cervical cancer screening. It is necessary to identify the exact underlying causes for this phenomenon, and systematic efforts are required to prevent unnecessary screening for women who have undergone a hysterectomy.

Pancreatic intra-epithelial neoplasia and histological grade of pancreatic cancer predict poor survival after pancreaticoduodenectomy

Pancreatic intra-epithelial neoplasia and histological grade of pancreatic cancer predict poor survival after pancreaticoduodenectomy