Detection Of Cervical Intraepithelial Neoplasia Research Articles

Computer-Aided Cervical Cancer Diagnosis Using Time-Lapsed Colposcopic Images.

Cervical cancer causes the fourth most cancer-related deaths of women worldwide. Early detection of cervical intraepithelial neoplasia (CIN) can significantly increase the survival rate of patients. In this paper, we propose a deep learning framework for the accurate identification of LSIL+ (including CIN and cervical cancer) using time-lapsed colposcopic images. The proposed framework involves two main components, i.e., key-frame feature encoding networks and feature fusion network. The features of the original (pre-acetic-acid) image and the colposcopic images captured at around 60s, 90s, 120s and 150s during the acetic acid test are encoded by the feature encoding networks. Several fusion approaches are compared, all of which outperform the existing automated cervical cancer diagnosis systems using a single time slot. A graph convolutional network with edge features (E-GCN) is found to be the most suitable fusion approach in our study, due to its excellent explainability consistent with the clinical practice. A large-scale dataset, containing time-lapsed colposcopic images from 7,668 patients, is collected from the collaborative hospital to train and validate our deep learning framework. Colposcopists are invited to compete with our computer-aided diagnosis system. The proposed deep learning framework achieves a classification accuracy of 78.33%-comparable to that of an in-service colposcopist-which demonstrates its potential to provide assistance in the realistic clinical scenario.

Analysis of the role of the human papillomavirus 16/18 E7 protein assay in screening for cervical intraepithelial neoplasia: a case control study

BackgroundCervical cancer is the second-most common gynecological cancer, early screening plays a key role in the diagnosis and treatment of cervical intraepithelial neoplasia (CIN). Sustained E7 protein expression is the pathological basis for CIN and cervical cancer.MethodsWe collected the cervical cell samples of women who visited the gynecological clinic of Peking Union Medical College Hospital between September 2018 and September 2019 and submitted them to the high-risk human papillomavirus (Hr-HPV) test. We performed a magnetic particle–based chemiluminescence enzyme immunoassay to analyze the HPV16/18 E7 protein level in CIN of different severities and compared the results with those of cervical pathology (gold standard) and the HPV test.ResultsThe positive rate of HPV16/18 E7 protein increased with the severity of CIN: 26.6% in normal tissue, 58.3% in CIN1, and 70.6% in CIN2 or higher (CIN2+). For CIN2+, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the E7 protein were 70.6, 67.9, 52.2, and 82.3%, respectively. These values of the HPV test were 86.8, 44.5, 43.7, and 87.1%, respectively. With the combination of the E7 protein assay and HPV test, the specificity for diagnosing CIN2+ was 78.1%, which was significantly higher than that of the HPV test alone.ConclusionsHPV16/18 E7 protein level is correlated with the severity of CIN and has a high concordance rate with the pathological result. For cervical cancer screening, the combination of HPV16/18 E7 protein assay and HPV test improves the CIN diagnostic specificity, detection rate, and detection accuracy.

Management of low-grade cervical cytology in young women. Cohort study from Denmark

Objective Cytology findings of atypical squamous cells of unknown significance (ASCUS) or low-grade squamous intraepithelial lesion (LSIL) are common among women under 30, but evidence on best management strategy is insufficient. We therefore investigated how different management strategies used in Denmark influenced biopsy rates and detection of cervical intraepithelial neoplasia (CIN). Methods Register-based cohort study including Danish women aged less than 30 years and born 1980–95, with ASCUS/LSIL as their first abnormal cervical cytology in 2008–16. Rates and relative risks (RR) of biopsy and detection of CIN3+, CIN2 and < CIN2 during two years follow-up were compared between women referred directly to colposcopy after ASCUS/LSIL or undergoing additional testing, including mRNA or DNA test for high risk HPV or repeat cytology. Results 19,946 women with ASCUS and 19,825 with LSIL were included in the study of whom 92% had adequate information about follow-up. Among women referred directly to biopsy, CIN3+ was detected among 21%, CIN2 in 17%, while 62% had < CIN2. Repeating cytology after 6 months reduced the biopsy rate to 44% of which 53% had < CIN2. Biopsy rates with HPV test were 67% for DNA test, 77% with 14-type mRNA test and 58% with 5-type mRNA test. The detection of CIN3+ was somewhat higher, between 13% and 14% for the three HPV tests vs. 11% with repeat cytology. However, the detection of < CIN2 (not indicating treatment) also increased with RR 2.11 (95% CI 2.01–2.21) for 14-type mRNA test, 1.35 (95% CI 1.29–1.41) for 5-type mRNA test, and 1.86 (95% CI 1.76–1.97) with HPV DNA test. Conclusions The choice of management strategy influences both the detection rate for severe lesions (CIN3+) and the proportion of women followed up for potentially insignificant findings.

Evaluating the Performance of p16INK4a Immunocytochemistry in Cervical Cancer Screening.

PurposeWhen used for cervical cancer primary screening, liquid-based cytology (LBC) has a high specificity but a low sensitivity. For histological diagnosis of high-grade lesions, p16INK4a immunostaining has proven to be useful. Therefore, our objective was to evaluate the use of p16INK4a immuno-cytology as a primary screen and a secondary screen after primary high-risk human papillomavirus (hrHPV) screening or LBC screening.MethodsA total of 1197 cytology slides were immuno-stained using automatic p16INK4a staining system (PathCIN®p16INK4a) in two studies from cervical screening programs. In the primary screening study, 875 slides were randomly selected and analyzed for p16INK4a. In the secondary screening study, 322 of the remaining slides were chosen by virtue of being HPV 16/18+, other hrHPV+/LBC≥ASC-US, or HPV-negative/LBC ≥LSIL. The sensitivity and specificity for detection of cervical intraepithelial neoplasia 2/3 or worse (CIN2+/CIN3+) were compared based on p16INK4a, LBC and HPV test results.ResultsIn combining two studies, there were 431 cases with biopsy pathology. They included 83 cases with CIN2+ and 41 cases with CIN3+. The p16 positivity rate increased with pathologic and cytologic severity (P<0.0001). For primary screening: p16 immuno-cytology was more specific than HPV testing and was similar in sensitivity. Also, p16 immuno-cytology compared favorably with routine LBC (≥ASC-US or ≥LSIL) in sensitivity and specificity. For secondary screening: after LBC screening, “Triaging ASC-US with p16” gave a higher specificity and a similar sensitivity as compared to the “Triaging ASC-US with hrHPV” algorithm. After HPV primary screening, p16 immuno-cytology was more specific than LBC (≥ASC-US); the calculated colposcopy referral rate was also decreased by using p16 immuno-cytology as triage. Triage of “HPV16/18 and p16” had higher specificity and similar sensitivity as compared to triage of “HPV16/18 and LBC ≥ASC-US”.ConclusionFor primary screening, p16INK4a immuno-cytology compares favorably to routine LBC and HPV testing. p16INK4a immunostaining could be an efficient triage to reduce the colposcopy referral rate after primary hrHPV screening or LBC screening. Therefore, p16INK4a immuno-cytology may be applicable as a favorable technology for cervical cancer screening.

Artificial intelligence-assisted cytology for detection of cervical intraepithelial neoplasia or invasive cancer: A multicenter, clinical-based, observational study

ObjectiveArtificial intelligence (AI) could automatedly detect abnormalities in digital cytological images, however, the effect in cervical cancer screening is inconclusive. We aim to evaluate the performance of AI-assisted cytology for the detection of histologically cervical intraepithelial lesions (CIN) or cancer. MethodsWe trained a supervised deep learning algorithm based on 188,542 digital cytological images. Between Mar 13, 2017, and Oct 20, 2018, 2145 referral women from organized screening were enrolled in a multicenter, clinical-based, observational study. Cervical specimen was sampled to generate two liquid-based slides: one random slide was allocated to AI-assisted reading, and the other to manual reading conducted by skilled cytologists from senior hospital and cytology doctors from primary hospitals. HPV testing and colposcopy-directed biopsy was performed, and histological result was regarded as reference. We calculated the relative sensitivity and relative specificity of AI-assisted reading compared to manual reading for CIN2+. This trial was registered, number ChiCTR2000034131. ResultsIn the referral population, AI-assisted reading detected 92.6% of CIN 2 and 96.1% of CIN 3+, significantly higher than or similar to manual reading. AI-assisted reading had equivalent sensitivity (relative sensitivity 1.01, 95%CI, 0.97–1.05) and higher specificity (relative specificity 1.26, 1.20–1.32) compared to skilled cytologists; whereas higher sensitivity (1.12, 1.05–1.20) and specificity (1.36, 1.25–1.48) compared to cytology doctors. In HPV-positive women, AI-assisted reading improved specificity for CIN1 or less at no expense of reduction of sensitivity compared to manual reading. ConclusionsAI-assisted cytology may contribute to the primary cytology screening or triage. Further studies are needed in general population.

Benefit and burden in the Dutch cytology-based vs high-risk human papillomavirus-based cervical cancer screening program

In 2017, the Dutch cervical cancer screening program had replaced the primary cytology-based screening with primary high-risk human papillomavirus-based screening, including the opportunity to participate through self-sampling. Evaluation and balancing benefit (detection of high-grade cervical intraepithelial neoplasia) and burden of screening (unnecessary referrals, invasive diagnostics, and overtreatment) is needed. This study aimed to compare the referral rates, detection of high-grade cervical intraepithelial neoplasia, overdiagnosis, and overtreatment in the new high-risk human papillomavirus-based screening program, including physician-sampled and self-sampled material, with the previous cytology-based screening program in the Netherlands. A retrospective cohort study was conducted within the Dutch population-based cervical cancer screening program. Screenees with referrals for colposcopy between 2014 and 2015 (cytology-based screening) and 2017 and 2018 (high-risk human papillomavirus-based screening) were included. Data were retrieved from the Dutch Pathology Registry (PALGA) and compared between the 2 screening programs. The main outcome measures were referral rate, detection of high-grade cervical intraepithelial neoplasia or worse, overdiagnosis (cervical intraepithelial neoplasia grade 1 or less in the histologic specimen), and overtreatment (cervical intraepithelial neoplasia grade 1 or less in the treatment specimen). Of the women included in the study, 19,109 received cytology-based screening, and 26,171 received high-risk human papillomavirus-based screening. Referral rates increased from 2.5% in cytology-based screening to 4.2% in high-risk human papillomavirus-based screening (+70.2%). Detection rates increased to 46.2% for cervical intraepithelial neoplasia grade 2 or worse, 32.2% for cervical intraepithelial neoplasia grade 3 or worse, and 31.0% for cervical cancer, and overdiagnosis increased to 143.4% with high-risk human papillomavirus-based screening. Overtreatment rates were similar in both screening periods. The positive predictive value of referral for detection of cervical intraepithelial neoplasia grade 2 or worse in high-risk human papillomavirus-based screening was 34.6% compared with 40.2% in cytology-based screening. Women screened through self-sampling were at higher risk of cervical intraepithelial neoplasia grade 2 or worse detection (odds ratio, 1.38; 95% confidence interval, 1.20-1.59) and receiving treatment (odds ratio, 1.31; 95% confidence interval, 1.16-1.48) than those screened through physician-sampling. Compared with cytology-based screening, high-risk human papillomavirus-based screening increases detection of high-grade cervical intraepithelial neoplasia, with 462 more cervical intraepithelial neoplasia grade 2 or worse cases per 100,000 women but at the expense of 850 more cases per 100,000 women with invasive diagnostics indicating cervical intraepithelial neoplasia grade 1 or less.

P16/Ki-67 Immunostaining in the Triage of Postmenopausal Women With Low-Grade Cytology Results.

The interpretation of postmenopausal smears and the gynecological treatment of these patients can often be difficult. The objective of this study was to assess the performance of p16/Ki-67 dual-stained cytology as a triage of atypical squamous cells of undetermined significance and low-grade intraepithelial lesion cytology results in postmenopausal women. All consecutive atypical squamous cells of undetermined significance and low-grade intraepithelial lesion smears in 1-year period were collected and p16/Ki-67 immunostaining was performed retrospectively. The results were compared with histology results or long-term cytology follow-up in cases with no biopsy. The sensitivity of p16/Ki-67 immunostaining for the detection of cervical intraepithelial neoplasia (CIN) 2 and CIN 3 was 57.1% and 85.0%, respectively. The specificity for the detection of CIN 2 was 94.3% and CIN 3 92.4%. Negative predictive values for the detection of CIN 2 and CIN 3 were 96.3% and 99.6%, respectively. Dual p16/Ki-67 immunostaining is a useful additional method in postmenopausal patients with low-grade cytology. Considering the high specificity and negative predictive value in our study, we believe that it could be helpful in avoiding unnecessary referrals to colposcopy and thus reduce the cost of the program.

Analysis of the efficacy of liquid-based cytology combined with HPV genotypes in screening cervical lesions in women of different ages

Abstract Objectives To evaluate the value of liquid-based cell examination combined with human papillomavirus (HPV) genotypes in the detection of cervical intraepithelial neoplasia. Methods A total of 21,155 patients who had undergone cytology, HPV genotypes and colposcopy-guided biopsy were grouped into three groups. Sensitivity, specificity, positive predictive value, and negative predictive value of the test methods of the three groups were compared. Results In the age group of less than 50 years, the sensitivity of HPV genotype testing was significantly higher than that of liquid-based cytology. The specificity of liquid-based cytology was significantly higher in all age groups than that of HPV genotype testing. The positive predictive value of each test index was higher in the age group less than 30 years, and the negative predictive value was higher in the 30–50-year age groups. In different age groups, liquid-based cytology and HPV genotype combined method can improve the sensitivity of detection and negative predictive values. Conclusions The HPV test has higher sensitivity and negative predictive value, and the cytology method is relatively specific and less sensitive. The combined method has better sensitivity and negative predictive value.

The Risk of Cervical Cancer After Cervical Intraepithelial Neoplasia Grade 3: A Population-Based Cohort Study With 80,442 Women

(Abstracted from Gynecol Oncol 2020;157:195–201) Cervical cancer screening programs and prophylactic high-risk human papillomavirus have significantly decreased the incidence and increased early detection of cervical intraepithelial neoplasia (CIN), which can progress to cervical cancer if left untreated. Surgical excision of CIN is very effective; however, research shows that women who have previously treated CIN are at an increased risk for developing cervical cancer compared with the general population.

The use of micro RNA in the early detection of cervical intraepithelial neoplasia

An important issue in current oncological research is prevention as well as early detection of cancer. This includes also the difficulty to predict the progression of early or pre-cancerous lesions to invasive cancer. In this context, the characterization and categorization of pre-neoplastic lesions of squamous cell carcinoma [cervical intraepithelial neoplasia (CIN)] are an important task with major clinical impact. Screening programs are worldwide established with the aim to detect and eradicate such lesions with the potential to develop untreated into cervical cancer. From the literature it is known that around 5% of CIN 2 and 12% of CIN 3 cases will progress to cancer. The use of molecular markers extracted from cervical mucus might help to identify these high-risk cases and to exclude unnecessary biopsies or surgical treatment. Here we can show that micro RNA (miRNA) analysis from cervical mucus of 49 patients allowed us to distinguish between healthy patients and patients with CIN 3. The miRNA panel used in combination allowed for highly significant testing (P < 0.0001) of CIN 3 status. In parallel, the human papillomavirus status of the patients, the most important factor for the development of cervical cancer, significantly correlated with the miRNA markers hsa-miR-26b-5p, hsa-miR-191-5p and hsa-miR-143-3p, a subpanel of the original six miRNAs. We provide here a proof-of-concept for cervical mucus-based testing for pre-neoplastic stages of cervical squamous cell carcinoma.

Test Accuracy of Human Papillomavirus in Urine for Detection of Cervical Intraepithelial Neoplasia.

The objective was to assess the diagnostic test accuracy of high-risk human papillomavirus (hrHPV) testing of self-collected urine and cervicovaginal samples for the detection of cervical intraepithelial neoplasia grade 2 or higher (CIN2+). We recruited a convenience sample of women 25 to 65 years of age who were undergoing clinically indicated colposcopy at two medical centers in North Carolina between November 2016 and January 2019. Women with normal cytology results and positive hrHPV results were also recruited. Urine samples, self-collected cervicovaginal samples, provider-collected cervical samples, and cervical biopsy samples were obtained from all enrolled women. Samples were tested for hrHPV DNA using the Onclarity assay (Becton Dickinson, Sparks, MD). Biopsy samples were histologically graded as CIN2+ or <CIN2. We calculated the sensitivity and specificity for detection of CIN2+ and assessed agreement between sample collection methods. We included 307 women (median age, 36 years) with valid histology results and triple-matched urine, self-collected cervicovaginal, and provider-collected cervical hrHPV results; 83 women (27%) had CIN2+. Urine-based hrHPV testing correctly identified 80% of CIN2+ cases (95% confidence interval [CI], 71 to 88%) using the PCR cycle threshold (CT ) established for provider-collected cervical samples, but sensitivity remained below the estimates for self-collected cervicovaginal and provider-collected cervical samples (both 94% [95% CI, 89 to 99%]). Using a higher CT cutoff value of ≤40, 90% sensitivity was achieved for urine-based hrHPV testing. Agreement between results for urine samples and self-collected cervicovaginal samples (kappa = 0.58) or provider-collected cervical samples (kappa = 0.54) was moderate. Urine-based hrHPV testing may be a promising approach to improve cervical cancer screening coverage, especially among women with limited access to health care.

Анализ результатов кольпоскопии в диагностике неоплазий шейки матки

The work is devoted to the actual problem of medicine — cervical intraepithelial neoplasia. The authors found that a group of women with cervical intraepithelial neoplasia is a patient of working age, and early detection of cervical intraepithelial neoplasia can prevent the development of invasive cancer, considered as one of the main causes of disability and female mortality. In gynecological practice, the most accessible and informative method for cervical intraepithelial neoplasia diagnosing is colposcopy.

Clinical and Analytical Performance of the BD Onclarity HPV Assay with SurePath Screening Samples from the Danish Cervical Screening Program Using the VALGENT Framework.

The Validation of HPV Genotyping Tests (VALGENT) framework is an international cooperation designed to evaluate human papillomavirus (HPV) assays with genotyping capabilities. Here, we assessed the performance of the BD Onclarity assay using Danish SurePath cervical screening samples collected under the fourth VALGENT installment, consisting of 998 consecutive samples from a screening population and 297 enriched samples with abnormal cytology (100 with atypical squamous cells of undetermined significance [ASCUS], 100 with low-grade squamous intraepithelial lesions [LSIL], and 97 with high-grade squamous intraepithelial lesions [HSIL]). The Onclarity assay detects six HPV genotypes individually (genotypes 16, 18, 31, 45, 51, and 52) and eight genotypes in three bulks (genotypes 33 and 58; genotypes 56, 59, and 66; and genotypes 35, 39, and 68). The clinical performance of the Onclarity assay for the detection of cervical intraepithelial neoplasia of grade 2 or worse (≥CIN2) and of two consecutive cytology outcomes negative for intraepithelial lesion or malignancy (2×NILM) was assessed relative to that of the GP5+/6+ PCR-enzyme immunoassay (GP-EIA) by a noninferiority test. The relative sensitivity for ≥CIN2 was 1.00 (95% confidence interval [CI], 0.97 to 1.04), and the relative specificity for 2×NILM was 1.04 (95% CI, 1.02 to 1.06). The Onclarity assay was found to be noninferior to the GP-EIA in terms of both sensitivity (P = 0.0006) and specificity (P < 0.0001). The type-specific performance of the Onclarity assay was also assessed, using the GP5+/6+ PCR with Luminex genotyping (GP-LMNX) as the comparator. The Onclarity assay showed good concordance for almost all HPV genotype groups. A stability analysis of SurePath samples was also performed, where a SurePath aliquot was stored refrigerated for 7 months and the internal control of the Onclarity assay was used as a marker for cellularity. The threshold cycle (CT ) value was the same (24.8) in the first and second Onclarity runs, showing that a SurePath sample can be stored refrigerated for 7 months and still remain a valid test specimen.

To Evaluate the Role of p16Ink4a Immunocytochemistry for Detection of CIN2+ in Women Detected Screen Positive by Visual Inspection Using Acetic Acid.

Objective:To evaluate the role of p16Ink4a immunostaining for the detection of cervical intraepithelial neoplasia (CIN2+) in women who had a positive screening test using visual inspection with acetic acid (VIA).Methods:Opportunistic screening of women (30–50 years) coming to the gynecology clinic by VIA was performed; the screen-positive women were included in the study which had the institutional review board (IRB) approval. A cytology slide for p16Ink4a immunostaining, colposcopy, and biopsy was then performed sequentially. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of p16Ink4a immunocytochemistry were evaluated with histopathology as the gold standard.Results:p16Ink4a positivity showed a linear correlation with the increasing grade of CIN. p16Ink4a positivity was seen in 6% of CIN 1, 80% of CIN 2, 100% of CIN 3, and squamous cell carcinoma. The sensitivity and specificity of p16Ink4a immunocytochemistry for detecting CIN 2 or more was 87.5% (95%CI 61.65–98.45) and 97.06% (95%CI 84.67–99.93). Colposcopy had an equal sensitivity of 87.5% (95% CI 61.65–98.45) and specificity of 50% (95% CI 32.43–67.57), respectively.Conclusion:With high sensitivity and specificity, p16Ink4a immunocytochemistry could be a viable option for triaging VIA-positive women.

When risk becomes illness: The personaland socialconsequences of cervical intraepithelial neoplasia medical surveillance.

BackgroundAfter the early detection of cervical intraepithelial neoplasia (CIN), medical surveillance of the precancerous lesions is carried out to control risk factors to avoid the development of cervical cancer.ObjectiveTo explore the effects of medical surveillance on the personal and social lives of women undergoing CIN follow-up and treatment.MethodologyA generic qualitative study using a poststructuralist perspective of risk management was carried out in a gynecology clinic in a public hospital of the Galician Health Care System (Spain). Participants were selected through purposive sampling. The sample consisted of 21 women with a confirmed diagnosis of CIN. Semistructured interviews were recorded and transcribed, and a thematic analysis was carried out, including researcher triangulation to verify the results of the analysis.FindingsTwo main themes emerged from the participants’ experiences: CIN medical surveillance encounters and risk management strategies are shaped by the biomedical discourse, and the effects of “risk treatment” for patients include (a) profound changes expected of patients, (b) increased patient risk management, and (c) resistance to risk management. While doctors’ surveillance aimed to prevent the development of cervical cancer, women felt they were sick because they had to follow strict recommendations over an unspecified period of time and live with the possibility of a life-threatening disease. Clinical risk management resulted in the medicalization of women’s personal and social lives and produced great uncertainty.ConclusionsThis study is the first to conceptualize CIN medical surveillance as an illness experience for patients. It also problematizes the effects of preventative practices in women’s lives. Patients deal with great uncertainty, as CIN medical surveillance performed by gynecologists simultaneously trivializes the changes expected of patients and underestimates the effects of medical recommendations on patients’ personal wellbeing and social relations.

Combining HPV DNA load with p16/Ki-67 staining to detect cervical precancerous lesions and predict the progression of CIN1\u20132 lesions

BackgroundHuman Papilloma Virus (HPV) DNA tests are highly sensitive and can triage women with mild lesions, improving the prognosis and diagnosis of cervical lesions. However, additional efficient strategies should be developed to improve the specificity of these tests.MethodsThis study aimed to evaluate the clinical value of HPV DNA load in improving the diagnosis and prognosis of cervical lesions by p16/Ki-67 testing. Histological samples were collected from 350 women with HR-HPV genotyping and analyzed by qRT-PCR. Immunohistochemical staining was used to assess p16 and Ki-67 expression and clinical performance characteristics were calculated.ResultsOf the cases, 271 had detectable HR-HPV infection, in which HPV-16 was most prevalent (52.0%), followed by HPV-58 (22.5%). P16/Ki-67-positivity increased with histological severity but not for HR-HPV infection. Amongst the 13 HR-HPV genotypes, only HPV-16 (P = 0.016) and HPV-58 (P = 0.004) viral loads significantly correlated with lesion severity. The P16/Ki-67/HPV DNA load co-test indicated an increased sensitivity for the detection of cervical intraepithelial neoplasia (CIN) lesions compared to p16/Ki-67 staining in HPV-16 and/or 58 positive cases. Viral load did not improve the sensitivity of p16/Ki-67 co-test in non-HPV-16 or 58 positive cases. The clinical performance of the p16/Ki-67/HPV DNA load co-test was limited for the prediction of the outcome of CIN1 lesions. However, amongst the 12 HPV-16 and/or 58 positive CIN2 cases in which return visit results were obtained, the behavior of the lesions could be predicted, with a sensitivity, specificity, positive prediction rate (PPV), and negative prediction rate (NPV) of 0.667, 1, 1 and 0.5, respectively.ConclusionCombination of the assessment of HPV DNA load with the intensity of p16 and Ki-67 staining could increase the sensitivity of CIN lesion diagnosis and predict the outcome of CIN2 in patients with a HPV-16 and/or 58 infection.

Associations of Cervicovaginal Lactobacilli With High-Risk Human Papillomavirus Infection, Cervical Intraepithelial Neoplasia, and Cancer: A Systematic Review and Meta-Analysis.

Vaginal dysbiosis characterized by depleted lactobacilli is usually correlated with human papillomavirus (HPV) infection and cervical carcinogenesis, but the effect of the Lactobacillus genus and represented species on this process remains unclear. PubMed, EMBASE, and CENTRAL databases were searched up to February 15, 2019. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using a fixed-effect model and Review Manager (version 5.3) for Mac. Eleven studies comprising 1230 cases were included. Lactobacillus spp. was associated with the decreased detection of high-risk subtype (hr)HPV infection (OR = 0.64, 95% CI = 0.48-0.87, I2 = 6%), cervical intraepithelial neoplasia (CIN) (OR = 0.53, 95% CI = 0.34-0.83, I2 = 0%), and cervical cancer (CC) (OR = 0.12, 95% CI = 0.04-0.36, I2 = 0%). At the level of Lactobacillus species, Lactobacillus crispatus, but not Lactobacillus iners, was correlated with the decreased detection of hrHPV infection (OR = 0.49, 95% CI = 0.31-0.79, I2 = 10%) and CIN (OR = 0.50, 95% CI = 0.29-0.88, I2 = 0%). Cervicovaginal Lactobacillus spp. is associated with the decreased detection of hrHPV infection, CIN, and CC; L. crispatus may be the critical protective factor.

Detection of cervical intraepithelial neoplasia (CIN) by visual inspection of cervix with acetic acid (VIA) and its comparison to cervical cytology

Background: Cervical cancer is the second most common cancer in women throughout the world, and it is the leading cause of cancer death among women in underdeveloped countries like Bangladesh is preventable and curable if detected at and early stage using proper screening tools. This study was done to see the effectiveness of VIA and find out the CIN and introduce as a complementary to cytology for diagnosing precancerous form of cervix.&#x0D; Materials &amp; Methods: A total 175 subjects were studied &amp; relevant data of cervix related patients have been collected. The data regarding Pap smear, VIA and biopsy have been taken and collected data was analysis by SPSS.&#x0D; Results: Out of 175 Patients VIA positive 53 (30.3%), Pap smear reports, 84 (48.0%) had inflammatory findings and 38 (21.7%) had dysplasia and biopsy result 41(23.4%) CIN positive. Sensitivity of VlA was 90.2%, specificity 88.1%, PPV 69.8%, NPV 96.7% and accuracy 88.6%. Sensitivity of Pap smear reports was 80.5%, specificity 96.3%, PPV 86.8%, NPV 94.2% and accuracy 92.6%.&#x0D; Conclusion: Visual inspection of cervix after application of acetic acid (VIA) is valid as cytology test for the identification of pre-invasive cervical cancer (CIN). Thus VIA is a useful screening method of Cervical Intraepithelial Neoplasia lesion as Pap smear.&#x0D; TAJ 2018; 31(1): 15-20

MiR-152 may function as an early diagnostic and prognostic biomarker in patients with cervical intraepithelial neoplasia and patients with cervical cancer.

Previous studies have demonstrated that circulating miRNAs are effective biomarkers of various types of cancer. It has also been indicated that miR-152 is upregulated in cervical cancer. However, whether miR-152 may be used as an early detection method for patients with cervical cancer is yet to be elucidated. The results of the current study demonstrated that miR-152 levels were the lowest in healthy controls, high in patients with cervical intraepithelial neoplasia (CIN), and the highest in patients with cervical cancer. Furthermore, miR-152 levels in peripheral blood were higher in patients with high-grade CIN compared with those with low-grade CIN. It was also demonstrated that miR-152 levels increased as the clinical stage of cervical cancer advanced. Compared with healthy controls, squamous cell carcinoma antigen (SSC-Ag) levels were significantly higher in patients with cervical cancer. However, no significant differences were identified in patients with CIN, indicating that SCC-Ag could not be used for the early detection of CIN. In contrast, miR-152 was elevated along with SCC-Ag in patients with CIN and cervical cancer. Receiver operating characteristic (ROC) analysis demonstrated that miR-152 preferentially distinguished patients with CIN (95% confidence interval, 0.688-0.973; P<0.001) and patients with cervical cancer (95% confidence interval, 0.817-0.996; P<0.001) from healthy controls. Additionally, miR-152 levels were markedly reduced in patients with cervical cancer who received chemotherapy (28 patients) or chemotherapy and radiation therapy (22 patients). In conclusion, the level of miR-153 in peripheral blood may be utilized as an effective biomarker for the early detection of cervical cancer, thus decreasing the requirement for invasive cervical biopsies. Furthermore, it may be utilized to predict the most effective form of treatment for patients with cervical cancer.

COMPARATIVE ANALYSIS OF CONVENTIONAL AND LIQUID-BASED CYTOLOGICAL METHODS FOR CERVICAL SMEARS

Purpose. Comparative analysis of the diagnostic value of traditional cytology (TC) and liquid cytology (LC) in the identi­fication of cervical intraepithelial neoplasia (CIN) and cervical cancer (CC).Patients and methots. The study included 87 women aged 18 to 80 years. All women were referred with suspicion of CIN, or underwent a control cytological examination after treatment for CIN and cervical cancer. Smears were taken sep­arately from ecto-, endocervix and mixed. Various tools were used (trowel, brushes type D, F and Cervex-Brush Combi). Each patient was sampled at the same time by different types of instruments. All surveyed women were performed at the same time traditional and fluid cytology. Liquid preparations were prepared using SurePath™ technology (BD and Company, Netherlands, USA) and E‑Prep (Biodyne, South Korea). Traditional cytological preparations were stained ac­cording to the Pappenheim method, liquid preparations — by Papanicolaou. A comparative analysis of cytological and histological findings was carried out.Results. According to our data, the number of non-informative material practically coincides in the shopping center and in the LC, from the instruments used the best results were obtained when using a cytobrush of type D and a wood­en spatula. The frequency of detection of CIN squamous epithelium in the LC is somewhat less than in the shopping center (60% vs. 62%). This is due to the lack of experience in evaluating the life cycle drugs. Despite the fact that the overall frequency of CIN detection is somewhat lower in the LC than in the TC, the frequency of detection of high grade squamous intraepithelial lesion (HSIL) is higher in the LC (51% versus 46%). This is due to the fact that cellular elements are concentrated in a limited area and single small HSIL complexes that are missed in the shopping center are better detected in the LC. The sensitivity of the TC smear from the cervix was 96.2%, life cycle — 92.4%. The accuracy of the shopping center is 92%, the life cycle is 89.6%.Conclusion. LC is an alternative to traditional cytological examination in order to detect pretumor diseases and cervical cancer. For an objective assessment of liquid preparations, additional training of cytologists is necessary.