Thinprep Cytologic Test Research Articles

Automatic Classification of Cervical Cells Using Deep Learning Method

Cervical cancer is the fourth most prevalent disease among women. Prompt diagnosis and its management can significantly improve patients’ survival rates. Therefore, routine screening for cervical cancer is of paramount importance. Herein, we explore the potential of a deep learning model to automatically distinguish abnormal cells from normal cells. The ThinPrep cytologic test dataset was collected from the fourth central hospital of Baoding city, China. Based on the dataset, four classification models were developed. The first model was a 10-layer convolutional neural network (CNN). The second model was an advancement of the first model equipped with a spatial pyramid pooling (SPP) layer (CNN + SPP) to treat cell images based on their sizes. Based on the first model, the third model replaced the CNN layers with the inception module (CNN + Inception). However, the fourth model incorporated both the SPP layer and the inception module into the first model (CNN + inception + SPP). The performances of the four models are estimated and compared by using the same testing data and evaluation index. The testing results demonstrated that the fourth model yields the best performance. Moreover, the area under the curve (AUC) for module four was 0.997.

ZNF671 Methylation as a Potential Biomarker to Identify Women with Cervical Intraepithelial Neoplasms Type 3 and Worse

Background: Cervical screening aims to identify women with cervical intraepithelial neoplasia 3 (CIN3) and squamous cell carcinoma (SCC), termed as CIN3+. Identification of women with CIN3+ ensure that they can receive optimal treatment and prevent overtreatment. Studies have suggested that the higher degree of cervical lesions, the more accumulation of DNA methylation (SCC > CIN3 > CIN2 > CIN1). DNA methylation analysis as a triage for women in cervical scrapings is feasible, but finding novel biomarkers with high sensitivity and high specificity is still a challenge. Zinc finger protein 671 (ZNF671), a member of the KRAB-ZFP family of mammalian transcriptional repressors, was hypermethylation of its promoter and downregulated in SCC. Methods: We investigated methylation of PAX1 or ZNF671 and genotyping of high-risk human papillomavirus (hrHPV) for detection of CIN3+ in 1006 women underwent Thinprep Cytologic test (TCT) and biopsy under colposcopy. Real-time methylation-specific PCR (qMSP) was used to detect the level of PAX1m and ZNF671m. Bisulfite pyrosequencing, the gold standard for detecting DNA methylation, was also used to measure the level of ZNF671m in 532 subjects. Findings: Sensitivities and specificities for CIN3+ were respectively, 75.69% and 77.54% for PAX1m, 79.52% and 85.76% for ZNF671m. High sensitivity (89.39%) but low specificity (60.63%) was observed for hrHPV. The sensitivities and specificities of PAX1m or hrHPV were 90.28% and 59.09%, of ZNF671m or hrHPV were 93.13% and 63.19%, of PAX1m or ZNF671m were 77.44% and 75.93%, respectively. The sensitivities and specificities of PAX1m(Algorithm 1) or ZNF671m (Algorithm 2) combined with hrHPV for CIN3+ were 98.61% and 51.57%, 76.77% and 88.42%, respectively. Interpretation: Compared with PAX1m, the level of ZNF671m could separate women more accurately into high risk groups either combined hrHPV genotyping or analysis alone. ZNF671mmay serve as a potential biomarker to identify women with CIN3+. And we propose that ZNF671m might be applied as a triage test alone or combined hrHPV genotyping and contribute to the globalization of cervical cancer screening. Funding Statement: This research was supported by Chinese National Major Project for New Drug Innovation (2019ZX09201-002-006), the National Natural Science Foundation (NNSF) of China (81973401) and the Natural Science Foundation for Young Scientist of Hunan Province, China (2018JJ3829). Declaration of Interests: The authors declare that they have no competing interests. Ethics Approval Statement: This study was undertaken in accordance with the Declaration of Helsinki, and the protocol was approved by the Ethical Committee of Xiangya Hospital of Central South University, China. All patients gave written informed consent before participation in this study.

Prevalence and Genotype Distribution of High-Risk Human Papillomavirus Infection in Women with Abnormal Cervical Cytology: A Population-Based Study in Shanxi Province, China.

PurposeHigh-risk human papillomavirus (HR-HPV) infection is widely known as the major cause of cervical cancer and there are notable differences in HR-HPV prevalence and genotype distribution in different populations. Women with abnormal cervical cytology are at increased risk of cervical cancer; however, the genotype distribution of HR-HPV in women with abnormal cervical cytology remains unclear.MethodsA total of 2,300 women with abnormal cervical cytology (from 39,988 women completing a baseline survey in a cohort established during June 2014 to December 2014) were enrolled in this study. All participants gave informed consent and completed a questionnaire about characteristics related to HPV infection. HPV genotypes were identified using flow-through hybridization, and cytology was assessed by the ThinPrep cytological test. Data were analyzed using SPSS 22.0 for Windows.ResultsThe overall prevalence of HR-HPV in the 2,300 women with abnormal cervical cytology was 32%, with single and multiple HR-HPV infections making up 70.2% and 29.8%, respectively. The top-five HR-HPV genotypes were HPV16 (13.5%), HPV58 (5.7%), HPV52 (4.9%), HPV53 (2.5%), and HPV51 (2.3%). The prevalence of HR-HPV in atypical squamous cells of undetermined significance, low-grade squamous intraepithelial lesions, and high-grade squamous intraepithelial lesions or higher was 30.8%, 36.5%, and 54.9%, respectively, showing an increasing trend with severity of cervical cytology (χ2trend=13.952, p<0.001). The prevalence of HPV16 and HPV33 increased significantly with the degree of cytological abnormality. HR-HPV infection risk was statistically higher in women aged 35–45 years, with low education, infrequent bathing, multiple gravidity, multiple parity, history of gynecological diseases, and premenopause.ConclusionHR-HPV infection in women with abnormal cervical cytology was 32%, and the top-five HR-HPV genotypes were HPV16, HPV58, HPV52, HPV53, and HPV51 in Shanxi Province, China. These results shed light on demographic and behavioral characteristics related to HR-HPV infection in women with abnormal cervical cytology and provide an insight for the development of HPV vaccines.

Correlation between multi-type human papillomavirus infections and viral loads and the cervical pathological grade.

ObjectiveTo investigate the relationship between single/multiple HPV infections and cervical lesions, and the correlation between viral load and the degree of cervical lesions.MethodsA total of 27 284 patients who underwent testing for HPV were retrospectively screened and 3728 women were enrolled who tested positive for HPV when examined by liquid‐based ThinPrep cervical smear cytology test and diagnosed by histopathology at the Shanxi Provincial People's Hospital between May 2017 and March 2019. The genotype and viral load of HPV were determined by fluorescence quantitative polymerase chain reaction. Based on the pathological grade, the cervical lesions were stratified into three groups: chronic cervicitis/cervical intraepithelial neoplasia (CIN) I; CIN II/CIN III; and cervical cancer.ResultsThere were significant intergroup differences in the distribution of single and multiple HPV infections. There was a positive correlation between the viral load and cervical pathological grade when the infections were caused by HPV 16, 18, 31, 33, 51, 52, 53, and 58.ConclusionMulti‐type HPV infections are more likely to aggravate the degree of cervical lesions than single‐type infections. The HPV type‐dependent viral load is associated with the cervical pathological grade.

Severe cervical inflammation and high-grade squamous intraepithelial lesions: a cross-sectional study.

Inflammation has been reported as a facilitator in cervical oncogenesis, but the correlation between inflammation and cytological abnormality remains uncertain. The aim of this study was to investigate the correlation between inflammation and cytological abnormality. ThinPrep cytological test (TCT) was used to detect cervical cytological abnormalities and inflammation degrees of 46,255 women in this prospective cross-sectional study. Histopathological examination was used to define the cervical intraepithelial neoplasia (CIN) in patients with cervical cytological abnormalities. The study revealed that 8.87% (4102/46,255) of TCT results had cytological abnormalities. The 4102 included cases were classified as the case group, including atypical squamous cells (ASC), low-grade squamous intraepithelial lesions (LSIL) and high-grade squamous intraepithelial lesions (HSIL). Women with negative intraepithelial lesion or malignancy (NILM) were classified as the control group. About 88.83% (3644/4102) of women with cytological abnormalities showed inflammations. The rate of severe inflammation was significantly higher in the case group than the control group (23.86% vs. 2.0%, P = 0.000). Our results also showed that patients with severe inflammation had a significantly increasing incidence of cytological abnormality by 12.598 times and elevated the risk of HSIL by 756.47 times, compared to the inflammation negative group. Severe inflammation was positively related to HSIL. Patients with severe cervical inflammation should be given more follow-ups and regular examinations and treated more carefully than those with mild or no inflammation.

Triage human papillomavirus testing for cytology-based cervical screening in women of different ages in primary hospitals: A retrospective clinical study.

Cervical cancer is a serious global health problem. The objective of this study was to provide a suitable cytology-based cervical screening method in women of different ages in primary hospitals.This study was a retrospective cohort study that included 9765 women who underwent primary cytology-based cervical screening and were grouped by age (35–44, 45–54, and 55–64 years old). Patients with abnormal cytology on the primary cervical thin-prep cytologic test (TCT) were advised to undergo triage human papillomavirus (HPV) test. Furthermore, patients with positive outcomes of the 2 indices underwent cervical tissue biopsy. The positive rate of TCT and HPV was compared among the 3 defined age groups. The sensitivity, specificity, and positive predictive value of TCT and HPV were assessed.In total, 2.5% (241/9765) of women had atypical squamous cells of undetermined significance or worse by TCT. High-risk (HR)-HPV infection was found in 70 triage participants. Neoplastic changes were confirmed in 95 patients (95/437, 21.7%) by biopsies. Among the different age groups, the positive rate of abnormal cytology was significantly different (P = .003), and the positive rate of HR-HPV was similar (P = .299). The sensitivity of initial TCT testing to detect intraepithelial neoplasia was higher than that of triage HPV testing, whereas the specificity, the positive predictive value of triage HPV testing was higher than that of TCT. The Youden index of HPV testing was higher than that of TCT detection in the 3 age groups, namely 0.582 versus 0.432, 0.553 versus 0.228, and 0.416 versus 0.332, respectively.The results of this study indicate that TCT testing is suitable as a cervical cancer screening method for women ≥35 years old in primary hospitals. Triage testing for women with HR-HPV has a high negative predictive value, reduces the rate of misdiagnosis, seems to be an excellent triage method for repeat atypical squamous cells of undetermined significance, and reduces the number of referral colposcopies preventing unnecessary overtreatment. The results of this study provide a crucial foundation for a unified guideline cervical cancer screening for primary health care institutions.

Treatment of HPV Infection-Associated Low Grade Cervical Intraepithelial Neoplasia with 5-Aminolevulinic Acid-Mediated Photodynamic Therapy.

To investigate the efficacy of 5-aminoketovalic acid (5-ALA) photodynamic therapy (PDT) in the treatment of patients with low cervical intraepithelial neoplasia (CINI) combined with high-risk human papillomavirus ((HR-HPV), and the factors affecting the efficacy. 80 patients with CINI and HR-HPV infection were selected for the study. They received once weekly 5-ALA-PDT for either three or six treatments. To evaluate the clinical efficacy of 5-ALA-PDT treatment, follow-up evaluations were conducted at 3, 6 and 12 months, utilizing thinPrep cytology test(TCT)and colposcopic histopathological biopsy for the detection of HPVDNA. Following PDT, HR-HPV remission rates at 3, 6 and 12 months were 75.32%, 80.52%, and 81.82%, respectively. Complete remission rate of CINI was 94.81% (73/77 patients). There was no statistically significant difference in the remission rate of HR-HPV between 3 and 6 treatments with PDT (P > 0.05). Likewise, there was no difference in the remission rate comparing patients ≤40 years old and those >40 years old (P > 0.05). However, the remission rate was statistically greater in patients with normal vaginal microecology compared to patients with vaginal microecologic imbalance (P = 0.004). Not only can 5-ALA-PDT effectively clear CINI, but it also can clear HR-HPV. Vaginal microecological imbalance can reduce the effect of PDT on HR-HPV, whereas differences in age or frequency of PDT do not affect the remission rate of PDT on HR-HPV.

Evaluation of the accuracy of colposcopy in detecting high-grade squamous intraepithelial lesion and cervical cancer.

The primary aim of this study was to evaluate the diagnostic accuracy of colposcopy in identifying high-grade squamous intraepithelial lesion or worse (HSIL+) and the characteristic performance of colposcopic images with various severity levels of cervical lesions. The medical records from 1828 women who underwent colposcopy at Affiliated Hospital of Tongji University from February 2016 to March 2019 were reviewed. Human papilloma virus (HPV) GenoArray test kit (HybriBio Ltd) and Thinprep cytologic test (TCT, Hologic, USA) were used to perform HPV genotyping and cytology. All colposcopic images were collected from the standard-of-care colposcope (Leisegang 3ML LED) and evaluated based on the 2011 International Federation of Cervical Pathology and Colposcopy (IFCPC) Colposcopy Standards. The linear by linear association, Pearson χ2 test, χ2 test, Kappa test, McNemar test and risk test were used to perform statistical analyses. The consistency between colposcopy and biopsy pathology was 59.35% with the moderate strength of kappa coefficient of 0.464. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of colposcopy and cytology for HSIL+ were 56.29%, 93.82%, 77.47%, 85.04% and 37.13%, 98.49%, 90.29%, 80.58%, respectively. The colposcopic features of HSIL+ were as follows: (1) thick or bulgy acetowhite epithelium with sharp border; (2) completely nonstained of Lugol's iodine; (3) type III/IV/V of gland openings; (4) punctation or atypical vessels. The data and findings herein provide the resource for evaluating the diagnostic value of colposcopy, and suggested that the accuracy of colposcopy is required to be further improved.

Artificial classification of cervical squamous lesions in ThinPrep cytologic tests using a deep convolutional neural network.

The diagnosis of squamous cell carcinoma requires the accurate classification of cervical squamous lesions in the ThinPrep cytologic test (TCT). It primarily relies on a pathologist's interpretation under a microscope. Deep convolutional neural networks (DCNN) have played an increasingly important role in digital pathology. However, they have not been applied to diverse datasets and externally validated. In the present study, a DCNN model based on VGG16 and an ensemble training strategy (ETS) based on 5-fold cross-validation was employed to automatically classify normal and abnormal cervical squamous cells from a multi-center dataset. First, we collected a dataset comprising 82 TCT samples from four hospitals and fine-tuned our model twice on the dataset with and without the ETS. Then, we compared the classifications obtained from the models with those provided by two skilled pathologists to discriminate the performance of the models in terms of classification accuracy and efficiency. Finally, paired sample t-tests were used to validate the consistency between the classification provided by the proposed methods and that of the pathologists. The results showed that ETS slightly, though not significantly, improved the classification accuracy compared with that of the pathologists: P0=0.387>0.05 (DCNN without ETS vs. DCNN with ETS), P1=0.771>0.05 (DCNN with ETS vs. pathologist 1), P2=0.489>0.05 (DCNN with ETS vs. pathologist 2). The DCNN model was almost 6-fold faster than that of the pathologists. The accuracy of our automated scheme was similar to that of the pathologists, but a higher efficiency in the accurate identification of cervical squamous lesions was provided by the scheme. This result allows for wider and more efficient screening and may provide a replacement for pathologists in the future. Future research should address the viability of the practical implementation of such DCNN models in the laboratory setting.

The value of p16(INK4a) cytology for early diagnosis of cervical cancer

Objective: To investigate the use of p16(INK4a) immuno-stained cytology as the primary screening for cervical cancer prevention. Methods: From March to August 2018, 902 women from Shenzhen and surrounding area were recruited for cervical cancer screening with ThinPrep Cytologic Test (TCT), cobas4800 HPV test, and p16(INK4a) co-test. Colpo/biopsies were performed using the point of interest biopsy protocol of directed and random cervical biopsies plus endocervical curettage for all women, any of whose tests was positive. Two senior cytopathologists interpreted TCT and p16(INK4a) test. The performance of p16(INK4a) for early detection of CIN2+ and inter-observer reproducibility of the interpretation of p16(INK4a) were evaluated. Results: The positive rates of HPV test, p16(INK4a) co-test and TCT diagnosed as LSIL/AGC or higher grade were 8.1% (73/902), 6.8% (61/902) and 4.7% (42/902), respectively. Colposcopy referring rate was 79.6% (109/137), among which 10 cases were diagnosed as CIN2+ (5 cases of CIN2 and 5 cases of CIN3). The sensitivity and specificity for CIN2+ of p16(INK4a) test, TCT (LSIL/AGC or higher grade) and HPV test were 90.0%, 80.0%, 100.0% and 90.9%, 91.9%, 82.5%, respectively. Compared to TCT and HPV test, there was no significant difference in sensitivity and specificity between p16(INK4a) and TCT/HPV test (P>0.05). The Kappa value of the 2 cytopathologists in interpreting p16(INK4a) and TCT was 0.944 and 0.425, respectively (P<0.05). Conclusions: p16(INK4a) for cervical cancer screening is equally sensitive to HPV test and specific to TCT while subjective difference of cytopathologists' interpretation of p16(INK4a) is small. Therefore, p16(INK4a) can be used as a new cervical cancer screen method for its better diagnostic performance.

An Abnormal Precone Endocervical Curettage Result Is an Independent Risk Factor for Positive Margins in Conization Specimens

Objective: This study aimed to identify risk factors associated with the presence of positive surgical margins in cervical conization specimens. Methods: This study is a retrospective analysis of data from women who had undergone conization for cervical intraepithelial neoplasia (CIN) from 2012 to 2018 at Fujian Maternity and Child Health Hospital. Factors extracted from the database included age, gravidity, parity, menopausal status, precone Thinprep cytology test, human papillomavirus (HPV) test, precone biopsy, precone endocervical curettage (ECC) result, conization method, operating surgeon, cone dimension, and pathology of the conization specimen, including grade of CIN, margin status and glandular involvement. Univariate and multivariate analyses were performed to identify risk factors associated with positive margins. Results: Data from 495 women were analysed. The proportion of positive margins was 24.85% overall, which varied according to the conization method (27.22% for loop electrosurgical excision procedure vs. 18.52% for cold-knife conization, p = 0.047) and was increased as the severity of the treated lesion increased (10.07% for CIN2 vs. 30.62% for CIN3, p < 0.001). HPV-16 genotype infection, abnormal precone ECC result, higher grade of biopsy, larger cone length and volume, and glandular involvement were significantly associated with positive margins on univariable analysis. After logistic regression analysis, only an abnormal precone ECC result (odds ratio 1.952; 95% confidence interval 1.037–3.676; p = 0.038) remained significant. Conclusions: In the present study, an abnormal precone ECC result was identified as an independent risk factor for positive margins in cervical conization specimens. More aggressive treatment may be considered in patients with abnormal precone ECC results in clinical practice.

Real time quantitative methylation detection of PAX1 gene in cervical cancer screening

IntroductionDNA methylation is currently found to be associated with the progression of cervical intraepithelial neoplasia and the development of cervical cancer. The aim of this study was to analyze the...

The application value of PAX1 and ZNF582 gene methylation in high grade intraepithelial lesion and cervical cancer.

To investigate the possibility of using the methylation level of PAX1/ZNF582 gene as molecular marker to differentiate the progression of cervical cancer. From January 2016 to March 2018, 150 patients, who were admitted to Cervical Disease Diagnosis and Treatment Center of Xuzhu Maternity and Child Care Hospital, were enrolled in this study. Patients were classified into chronic cervicitis (for 19 cases), low-grade squamous intraepithelial lesion (LSIL) (18 cases), high-grade squamous intraepithelial lesion (HSIL) (37 cases) and squamous cell carcinoma (SCC) (31 cases). All patients underwent several tests including Thin-prep cytology test (TCT), HPV DNA detection and detection of methylation level of PAX1/ZNF582 genes. For diagnosis of HSIL, the area under curve (AUC) was 0.878 (95% CI 0.806 ~ 0.950); the threshold for PAX1 was 12.285, the sensitivity and specificity were 91.9% and 72.8%, respectively. The AUC of ZNF582 gene detection was 0.900 (95% CI 0.842 ~ 0.959), the threshold was 11.56, while the sensitivity and specificity were 97.3% and 76.7%, respectively. Among various tests we conducted, PAX gene detection methods showed the highest specificity (97.30%). PAX1/ZNF582 gene detection method demonstrated the highest accuracy. For patients with high-grade cervical lesion and cervical cancer, the methylation level of PAX1/ZNF582 gene could be applied as a noteworthy biomarker for diagnosis and for cervical cancer classification.

Evaluation of PCR-Reverse Dot Blot Human Papillomavirus Genotyping Test in Predicting Residual/Recurrent CIN 2+ in Posttreatment Patients in China.

ObjectiveTo assess the clinical value of the PCR-reverse dot blot human papillomavirus genotyping test during follow-up of patients with CIN grade 2 or worse (CIN 2+).MethodsFour hundred patients with CIN 2+ receiving treatment from January 2008 to January 2017 were included in our study. Postoperative follow-up procedures comprised HPV examination and cervical cytology every 3–6 months for the first 2 years and then followed up every 6–12 months. A pathology examination was performed when there was a positive funding for HPV 16/18 or an abnormal ThinPrep cytology test (TCT) with or without positive for HR-HPV according to the American Society for Coloscopy and Cervical Pathology (ASCCP) guidelines.ResultsThe median follow-up period was 27.10±12.47 months (ranging from 3 to 50 months). During follow-up, 12.00% (48/400) of the women developed residual/recurrent disease. The highest risk in CIN 2+ and CIN 3+ residual/recurrence was HPV-16/-18 (hazard ratio (HR)=12.898, 95% CI= 6.849–24.289; HR= 20.726, 95% CI= 9.64–44.562, respectively). Among the different follow-up methods, type-specific (TP) HR-HPV persistent infection showed the highest cumulative incidence risk (CIR) (84.62%, 95% CI=73.29–95.94) and HR (5.38, 95% CI= 2.596–11.149) during the 4-year follow-up period. At the CIN 2+ and CIN 3+ endpoints, TP-HPV testing had relatively high sensitivity (84.62%, 95% CI=73.29–95.94 and 89.28%, 95% CI= 77.83–100.00, respectively) and specificity (78.07%, 95% CI= 72.70–83.44 and 75.73%, 95% CI= 70.30–81.17, respectively). However, at the CIN 2+/CIN 3+ endpoint, TCT follow-up had a sensitivity of 60.42%/62.16% (95% CI=46.58–72.25/46.54–77.79) and specificity of 90.18%/88.72% (95% CI=86.95–93.41/85.35–92.10).ConclusionTP HR-HPV follow-up can provide a reliable and sensitive clinical reference for CIN 2+ postoperative patients.

Comparison of clinicopathological characteristics of endogenous and exogenous cervical cancer with its clinical significance

&lt;p class="abstract"&gt;&lt;strong&gt;&lt;span lang="EN-US"&gt;Background: &lt;/span&gt;&lt;/strong&gt;Cervical cancer is the third leading cause of cancer death in women of less developed countries due to poor screening and decreased diagnostic approaches. We aimed to investigate and differentiate the distinct clinicopathological characteristics and prevalence of endogenous and exogenous cervical in hospitalized patients&lt;span lang="EN-US"&gt;.&lt;/span&gt;&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;&lt;span lang="EN-US"&gt;Methods: &lt;/span&gt;&lt;/strong&gt;A study was performed contained 663 patients that were enrolled and underwent for screening of endogenous and exogenous cervical cancer in Qilu Hospital of Shandong University, from January 2010 to March 2015. &lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;&lt;span lang="EN-US"&gt;Results: &lt;/span&gt;&lt;/strong&gt;Our results indicated that combined examination of thin-prep liquid-based cytology test and human papillomavirus (HPV)-DNA are effective for diagnosis of endogenous and exogenous cervical cancer. The clinicopathological characteristics based on tumor growth pattern, and high risk HPV-DNA incidence had no significant difference (p&amp;gt;0.05) in endogenous and exogenous cervical cancer patients. The higher ratio of lymph node metastasis in endogenous cervical cancer and exogenous cervical cancer during IB1-stage (24.3% vs 12.9%), and in IIA2-stage (36.4% vs 25%) was observed respectively. In addition, our data provide compelling evidence that the level of deep interstitial infiltration, and lymphatic vascular infiltration in endogenous cervical cancer was collectively higher (82.7% and 33%) compared to exogenous cervical cancer (62.4% and 18.3%) respectively during all stages&lt;span lang="EN-US"&gt;.&lt;/span&gt;&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;&lt;span lang="EN-US"&gt;Conclusions: &lt;/span&gt;&lt;/strong&gt;The higher percentage of lymph node metastasis,&lt;strong&gt; &lt;/strong&gt;deep interstitial infiltration, and lymphatic vascular infiltration was observed in endogenous cervical cancer which might be the biomarker and differential key points for the diagnosis of endogenous cervical cancer. Taken together, our study provides clinicopathological features to diagnose, and differentiate the endogenous and exogenous type cervical cancer with its prevalence.&lt;/p&gt;

Evaluation of multiple screening methods for cervical cancers in rural areas of Xinjiang, China.

This study is to evaluate the screening methods of cervical cancers for rural females in Kash bachu, Xinjiang, China.A total number of 3000 married females were surveyed, and subjected to the gynecological examination. In these subjects, 1993 females received the careHPV (human papillomavirus) test, while 1007 females underwent the visual inspection with acetic acid (VIA) and visual inspection with Lugol's iodine (VILI). The subjects positive for careHPV detection were subjected to Cervista, Cobas 4800, and Aptima HPV detection, and Thinprep Cytologic Test (TCT). The subjects positive for 1 detection only received colposcopy cervical biopsy.A total of 569 subjects received the cervical biopsy, and the positive rate was 2.3% (69/3000), while the detection rate for CIN (cervical intraepithelial neoplasia) II and above levels was 1.13% (34/3000). Receiver operator characteristic (ROC) curve analysis showed that, the area under the curve (AUC) value for the careHPV test was 0.671, which was higher than the VIA/VILI (0.619), suggesting higher diagnostic value for the careHPV test. For the Cervista, Cobas 4800, Aptima HPV detection, and TCT methods, the highest AUC value was observed for the TCT method, indicating that the TCT method is the most valuable for the cervical cancer screening.The diagnostic value of careHPV test is superior to the VIA/VILA detection method. The TCT method has the greatest value for the cervical cancer screening. The Cervista HPV detection method should be considered where the conditions are limited.

Research of the potential biomarkers in vaginal microbiome for persistent high-risk human papillomavirus infection

Vaginal dysbiosis may paly role in increased risk of human papillomavirus (HPV) infection. This study aims to explore potential vaginal microbiome biomarkers, to predict persistent high-risk HPV (HR-HPV) infection and cervical intraepithelial neoplasia (CIN) 2+, and to find novel treatment targets for HPV infection. A total of 329 women aged 20-69 were enrolled in this study, including 59 with cervical persistent HPV infection irrespective of cytology status (group A), 139 with incident HPV infection (group B), and 131 without HPV infection (group C). Vaginal microbiome composition was determined by sequencing of barcoded 16S rDNA gene fragments (V4) on Illumina HiSeq2500. In genus level, the relative abundance of Prevotella, Porphyromonas and Enterococcus were significantly the highest in group A, while Bacteroides was the lowest in group A. In species level, we found the relative abundance of Prevotella bivia, Enterococcus durans and Porphyromonas uenonis were the highest in group A while Lactobacillus iners was significantly under-represented in group A than the other two, and Prevotella disiens was over-represented in group C than the other two groups. A predominance of Prevotella bivia, Enterococcus durans and Porphyromonas uenonis with a concomitant paucity of Lactobacillus iners and Prevotella disiens may relate to HPV persistent infection. Furthermore, the relative abundance of Prevotella bivia being over 0.05554% with Prevotella disiens being under 0.02196% may be a good predictor for appearance CIN2+ for those diagnosed with the other 12 types of HR-HPV persistent infection but normal ThinPrep cytology test (TCT) testing. The exact molecular mechanism of the vaginal microbiome in the course of persistent HR-HPV infection and cervical neoplasia should be further explored. Future research should include intervention of vaginal microbiome composition to reverse the course of HR-HPV infection and the natural history of cervical neoplasia.

P16/Ki-67 dual-stained cytology used for triage in cervical cancer opportunistic screening.

ObjectiveTo evaluate the efficiency of p16/Ki-67 dual stain used as a triage in cervical cancer screening.MethodsIn this study, we did 468 p16/Ki-67 dual stain in human papillomavirus (HPV) 16/18-positive or 12 other high-risk HPV (OHR-HPV) positive Thinprep cytologic test (TCT) atypical squamous cells of undetermined significance (ASCUS)/ lower-grade squamous intraepithelial lesion (LSIL) women. We evaluated the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of the triage test.ResultsThe sensitivity, specificity, PPV and NPV of p16/Ki-67 dual stain in HPV 16/18-positive women were 91.5%/68.4%, 77.0%/75.0%, 73.9%/59.1% and 92.8%/81.8%. In 12 OHR-HPV positive TCT ASCUS/LSIL women, the results were 79.1%/95.0%, 88.5%/66.7%, 88.5%/70.4% and 89.2%/94.1%. The risk of precancerous lesions in p16/Ki-67 dual stain positive cases was much higher than before, and the negative cases had lower risk. Besides, there was no cervical intraepithelial neoplasia (CIN) III case missed after triaged by p16/Ki-67 dual-stained cytology. In p16/Ki-67 dual-stained cytology positive women with benign pathology or CIN I, the 1-year progression rate is 20.5% and in p16/Ki-67 dual-stained cytology negative women, the 1-year progression rate is 5.6%.Conclusionshr-HPV genotyping test plays an important role in cervical cancer screening. p16/Ki-67 dual stain may be a promising triage test. As for chronic cervicitis or CIN I patients, a positive p16/Ki-67 dual-stained cytology suggests a high risk in progression and need to be followed up closely.

Clinical Observation of rhIL-2 Combined with Zhenqi Fuzheng and BaofuKang Suppository in the Treatment of Cervical Intraepithelial Neoplasia II with HPV Infection

Objective: To investigate the clinical effects of recombinant human interleukin-2 (rhIL-2) combined with Zhenqi Fuzheng and Baofukang on cervical intraepithelial neoplasia II (CINII) combined with human papilloma virus infection. Methods: There were 593 patients diagnosed with CINII with HPV infection, including 296 in the control group and 297 in the experimental group. The control group was given only Zhenqi Fuzheng oral and Baofukang suppository vaginal medicine. The experimental group was treated with rhIL-2 injection in addition to Zhenqi Fuzheng oral and Baofukang suppository vaginal medicine which is treated for 3 months. After 3 months, Thinprep cytologic test (TCT), human papilloma virus (HPV) quantitative examination and colposcopy biopsy were reviewed. Results: After 3 months of treatment, the negative conversion rate and total effective rate of HPV in the control group were 58.11% and 70.95% respectively, and the negative conversion rate and total effective rate of the experimental group were 79.46% and 90.57% respectively. There was significant difference between the two groups (p = 0.000). The curative rate of cervical lesions was significantly higher in the test group than in the control group, 89.56%, 68.91%, respectively. The statistical difference between the two groups is significant (p = 0.000). Conclusion: It has an essential clinical value that HPV infection patients and cervical intraepithelial neoplasia II associated with HPV infection patients are treated by rhIL-2 combined with Zhenqifuzheng and Baofukang, which is safe, effective, non-invasive, reusable advantages. However, the long-term efficacy and side effects need to be further studied.

Economic evaluation of fifteen cervical cancer screening strategies in rural China

Objective: To evaluate the feasible cervical cancer screening strategies in rural China. Methods: The study was based on the health industry scientific research project of National Health Commission in 2015, cervical cancer screening technology and demonstration research suitable for rural areas in China, we collected health economics and epidemiological parameters and established the unscreening model and screening model with Treeage Pro 2011 software. Combining with the data acquired from site investigation, including population screening, treatment-related clinical materials and cost data, we simulated the occurrence and the development of cervical cancer of rural women in China under different screening and intervention programs and predicted the screening effects [cumulative incidence, cumulative risk of disease, life years and quality adjusted life years (QALY) , gains] and costs after 20 years, and using health economic evaluation analysis (cost-effectiveness analysis, cost-utility analysis, cost-benefit analysis). Screening programs included five screening strategies [visual inspection with acetic acid/lugol's iodine (VIA/VILI), careHPV, ThinPrep cytology test (TCT), careHPV+TCT, careHPV+VIA/VILI] and three screening intervals (1-year, 3-year, 5-year), a total of fifteen screening programs. Results: Compared with no screening, fifteen screening programs reduced the cumulative incidence by 22.65%-51.76%. Compared with TCT or VIA/VILI, for the same screening interval, the reduced cumulative incidence, the amounts of life-year saved and QALY and benefits gained of careHPV were the highest. The cost-effectiveness ratios of these screening programs ranged (0.44-3.24)×10(4) Yuan per life-year saved, cost-utility ratios ranged (0.15- 1.01)×10(4) Yuan per QALY, benefit-cost ratios ranged 7.73-59.10. The results of incremental costeffectiveness ratios showed that VIA/VILI every five years, VIA/VILI every three years, careHPV every five years, careHPV every three years and careHPV every year were dominant programs. Conclusions: VIA/VILI screening is cost-effective, careHPV is slightly more expensive but more effective. In rural China, careHPV screening every five years could be recommended. This study provides a basis for the determination of cervical cancer screening methods feasible for rural areas in China.