Fuzzy-Based Classification for Cervical Dysplasia Using Smear Images

Alternative techniques for detecting cancer of the cervix uteri alongside its early precancerous lesions still remain necessary for low income environments since morbidity and mortality due to cervical cancer continues to be on the rise. We recruited one thousand and seventy-seven women aged 15-55 years from selected study hospitals in Eastern Uganda and examined them using Papanicolaou (Pap) smear, direct visual inspection with 5% acetic acid solution (VIA), and human papillomavirus (HPV) DNA testing. Study participants detected with high-grade lesions (HSIL) or cancer cells on Pap smear test, positive VIA test (acetowhite lesions, cervical ulcer or growth), and positive high-risk HPV DNA (relative light units (RLU) were immediately scheduled for colposcopy and cervical biopsy. Of the forty percent of the women confirmed with pap smear positive, 43 of the 63 women had invasive carcinoma (68.3%), while 89 out of 137 women with confirmed biopsy were diagnosed with high grade CIN (CIN2,3) (65%). DVI identified 46 of 63 carcinomas (73%) as well as 47 of 74 high grades CIN (CIN 2, 3) (64%). There was a variation in HPV DNA results due to the cutoff value considered in defining the final result. HPV DNA of high-risk HPV types was detected 39 (61.9%) out the 63 women diagnosed invasive cervical cancer, while 66 (73.3%) or 46 (51%) was detected in the biopsy of women diagnosed with high grade CIN (CIN 2,3). Similarity in identification of high-grade cervical abnormalities was registered by the testing methods. Both VIA and HPV genetic testing methods diagnosed similar numbers of high grade CIN 2,3 and invasive cancer cases as Pap smears. Nevertheless, individual test methods categorized study participants with no cervical disease as being positive. Key words: Visual inspection with acetic acid (VIA), cervical intraepithelial neoplasia (CIN), human papillomavirus (HPV).

Pap smears, also known as pap tests, can identify abnormal cells early that develop cervical cancer, allowing for timely intervention and treatment.Even though the incidence rate is reduced in this modern era, it poses a significant risk to human life and should be taken very seriously.An accurate and rapid system for classifying pap smear images is necessary to provide appropriate therapy.Deep Neural Networks (DNNs) have garnered much interest in recent years and have shown outstanding categorization results in computer vision.An efficient Pap Smear Image Classification (PSIC) system with Efficient Weight Regularization (EWR) in DNN is presented in this study.The main problem with neural networks is that they have large weights that overfit the training data.To overcome this difficulty, the EWR approach is employed to penalize the large weights using grid search.The proposed non-invasive support system detects pap-smear images with cancerous cells.The HERLEV dataset comprises 675 digitized abnormal images, and 242 normal images are utilized for the classification task.When using the capabilities of the EWR-DNN combination, the proposed PSIC system can work at its absolute best.The concepts described in this study also provide a possible path to increase the categorization accuracy of all medical diagnoses.Results show that the PSIC system, which employs EWR approach achieves 98.9% classification accuracy, 99.3% specificity and 98.5% sensitivity using a regularization parameter of 10 -3 .The comparison study with other deep learning models such as VGG, ResNet, AlexNet and GoogleNet also shows the superior performance of the PSIC system.

To identify cytologic parameters on Pap smears of women with an atypical squamous cells of undetermined significance (ASCUS) diagnosis that could help cytologists to indicate whether a particular ASCUS case is most likely related to cervical intraepithelial neoplasia (CIN) grade 1 or 2/3. A total of 360 eligible women diagnosed with ASCUS and referred to the colposcopy clinic of Saint-Sacrement Hospital participated in the study. Eligible women were those aged 18-50 years, newly diagnosed with ASCUS, with no history of cervical biopsies or treatment, and not pregnant at the time of the visit. Colposcopically directed biopsies of lesions were obtained. All Pap smears were reviewed according to 36 different cytomorphologic criteria. The regression logistic model was used to estimate the odds ratios (ORs) for the associations between cytologic criteria observed in smears and the diagnosis of CIN made on biopsies. All cytologic criteria significantly (P < .05) associated with CIN were entered in the models, and a backward selection was done to determine independent cytologic predictors of CIN 1 and 2/3. Biopsies revealed that 22.2% of the study population had concurrent CIN. CIN I and 2/3 were identified in 61 (16.9%) and 19 women (5.3%), respectively. Clear perinuclear spaces (OR = 2.5, P = .002) and moderate nuclear atypia (OR = 4.4, P = .02) were two cytologic criteria independently associated with CIN 1. Four independent predictors of CIN 2/3 were identified: the presence of clear perinuclear spaces (OR = 5.9, P = .004), hyperchromasia (OR = 3.9, P = .04), moderate anisokaryosis (OR = 13.1, P = .01 and increased nuclear volume of metaplastic cells (OR = 5.1, P = .007). These observations may help cytologists to better categorize ASCUS lesions as intraepithelial ones and will also contribute to improving the Bethesda definition of ASCUS. Further studies are planned to validate these observations.

BACKGROUND: Cervical intra-epithelial neoplasia (CIN) and cervical cancer remain important health problems for women worldwide. It is largely a preventable disease that is characterized by a long lead time. The objective of this study was to determine the frequency of precancerous lesions of cervix by Pap smear screening. METHODS: A retrospective hospital based study was conducted at Department of Pathology, in a Tertiary Care Institute and associated hospital, Bhopal. Data was collected from the records of Pap's smear testing done on 388 patients in years 2011 & 2012. Analysis was done by entering data in SPSS software and Chi-square test was applied to find statistical significance. RESULTS: Most common lesions on Pap's smear was Low grade squamous intraepithelial lesion (LSIL) in 104 (26.8%) of cases and High grade squamous intraepithelial lesion (HSIL) in 15 (3.9%) of cases. 44 (11.3%) were senile Atopic Changes, parasitic Infection in 27 (7%) of cases and 2 (0.5%) were carcinoma cervix cases. All the cervical lesions were most common in age of 31-40 yrs. and were significantly associated with age. CONCLUSIONS: Pap's smear examination information should be spread in community apart from hospitals. Especially the young women should be motivated for regular Pap's smear. Pap's smear is the single most important screening method for early detection of precancerous & cancerous cervical lesions.

Introduced in 1940, Pap smear test has proven to be an effective screening method to determine the different stages of cervical cancer. Identification and classification of Pap smear images to detect cervical cancer via manual screening is a challenging task for pathologists therefore increasing the chances of human error. In this paper, we propose an automatic method to detect and classify the grade of cervical cancer using both geometric and texture features of Pap smear images and classifying accordingly using multi SVM. The geometric features are obtained through segmentation of nucleus and cytoplasm using independent level sets, detecting whether the cell is cancerous or normal, with reference to the ground truth. By extracting well defined GLCM texture features and using a combination of PCA and the best class of multi SVM, the images are classified with an accuracy of 95%.

Evaluation of the over-treatment percentage when choosing a 'see and treat' approach in patients with de- viant cervical smear test results. The authors performed a retrospective chart review among women who were treated for cytological low-grade squamous intraepithelial lesion (LSIL) or high-grade squamous intraepithelial lesion (HSIL) from January 2009 until December 2010. All patients who were treated for deviant Pap-smears were analyzed. Patient characteristics were taken into account when performing the analysis. Data were analyzed using SPSS. Logistic regression was performed to determine the influence of age, smoking, and the reason to perform the Pap-smear. A total of 723 patients with deviant Pap-smear results were analysed. High-grade cervical intraepithelial neoplasia (CIN) was found in 70.3% of the patients with a Pap 3A average dysplasia (low-grade squamous intraepithelial lesion). This indicates that 29.7% of the patients would be over-treated with a 'see and treat' approach. For Pap 3B (high-grade intra-epithelial lesion) or higher the over-treatment percentage was 6.7% or less. Potential risks of a loop electrosurgical excision procedure (LEEP) on future pregnancies and fertility should be taken into account when treating fertile patients for potential CIN. This should be part of the counseling process of patients with a Pap 3A average dysplasia. A 'see and treat' approach can and probably should be proposed to patients with a Pap 3B or higher.

Detection and identification of cells in a Pap smear test is very important for determining cell abnormalities. Detection of cells becomes an important stage in early detection of cervical cancer. The presence of inflammatory cells in Pap smear images often results in the identification of nuclei in the early detection of cervical cancer in Pap smear image becomes difficult to do. The success of inflaming the inflammatory cells and detecting the nucleus will facilitate the process of identifying the nucleus. This will greatly help the development of information acquisition system technology and the classification of single Pap smear cell image for early detection of cervical cancer. The paper aims to compare three methods of nuclear detection and inflammatory cell in a single Pap smear image. The results of the comparison of nucleus and inflammatory cell in the test of data consisting of 84 images with inflammatory cells, showed that the K-Means and Bayesian classification method has not been able to accurately detect the nuclei and inflammatory cell, rather than the nuclei and inflammatory cells detection base on the combination of gray level thresholding method.

This study was conducted to evaluate 3 different methods, used alone or in combination, of screening for cervical intraepithelial neoplasia (CIN), and to compare the outcomes with colposcopic findings. Eight hundred nine patients were recruited to undergo cervical screening with visual inspection of the cervix using acetic acid (VIA), human papillomavirus (HPV) testing using hybrid capture II (HCII), and conventional Pap smear. Social and demographic information and clinical history were obtained at the enrollment visit by interview and questionnaire before pelvic examination. After collection of Pap and HCII samples, VIA was conducted 1 minute after application of 5% acetic acid to the cervix. Cervical abnormalities were recorded according to the Atlas of Visual Inspection. The presence of areas suggestive of condyloma, CIN 1, CIN 2, CIN 3, or cancer was recorded as positive VIA results. All patients underwent colposcopy after pelvic examination, and suspicious areas were biopsied. There were 99 (12%) patients with positive VIA results, of which 28% were suspected condyloma, 57% were thought to be CIN 1, 13% were suspicious for CIN 2/3, and one was a potential case of invasive cancer. In all, there were 57 (7%) positive Pap smear results, including 22 atypical squamous cells of undetermined significance (ASCUS) (38% of abnormalities), 20 low-grade squamous intraepithelial lesions (LSIL) (35%), 14 high-grade intraepithelial lesions (HSIL) (25%), and one diagnosis of atypical glandular cells (AGC) (2%). One smear was inadequate for evaluation. HPV testing identified 151 (19%) patients positive for high-risk HPV. In the final histologic diagnoses, 40 (5%) women had cervical neoplasia, including 29 CIN 1, 7 CIN 2, 3 CIN 3, and one invasive cancer. The sensitivity and specificity for each test alone or in combination are shown in Tables 1 and 2. For identifying CIN 2 or worse, HCII had the highest sensitivity (73%) and Pap smear was the most specific (93%). Together, Pap and HCII had the highest sensitivity (82%) for detection of CIN 2 or worse. The highest specificity was seen in the combination of VIA and Pap smear (83%).TABLE 1: Performance of VIA, Pap test and HCII in detecting CIN 1 or worse or/CIN 2 or worseTABLE 2: Association of screening methods in detecting CIN 1 or worse/CIN 2 or worse

PCN105 - Cost of Cervical Cancer and Cervical Intraepithelial Neoplasia in Croatia

Cervix intraepithelial neoplasia (CIN) refers to abnormal changes in the squamous cells of the cervix, with more significant changes known as high-grade squamous intraepithelial lesions (HSIL) occurring in grades II and III. The study aimed to estimate the prevalence of cervical intraepithelial neoplasia and explore potential risk factors for HSIL among women living in the Kurdistan region, Iraq. The research encompassed a sample size of 1300 female participants whose Papanicolaou (pap) smears were taken in several hospitals located within the Kurdistan region. The objective of the study was to determine the prevalence of cervical infection among these women. This was a multi-centre study conducted from January 2021 to the end of December 2021 for the determination of pap smears and the relationship between CIN and cervical cancer. Only 120 (9.23%) of those 1300 participants suffered from cervical or vaginal problems. A pap smear, also known as a pap test, is a routine screening procedure used to detect abnormal cervical cells that may indicate cervical cancer or precancerous conditions. The procedure involves collecting a sample of cells from the cervix. The most important details in this study are the age groups and percentages of women who have undergone a pap smear. There were four women who tested positive for cervical cancer, accounting for 3.33% of the 120 participants with cervical or vaginal problems. However, there were 116 (96.67%) women who tested negative. With regard to the distribution of inflammation rates among the participants with cervical or vaginal problems, there were 114 (95%) women who suffered inflammation, whereas there were six (5%) women without inflammation. In each age group, the numbers of women with and without cervical cancer, as well as the corresponding percentages, were considered.The data suggest that the incidence of cervical cancer tends to increase with age since higher percentages were observed in older age groups. The study highlights the importance of regular screenings and age-specific cervical cancer prevention and detection strategies to ensure early diagnosis and effective medical interventions. The prevalence of cervical cancer cases was relatively low, with only 0.31% of the total participants diagnosed with cervical cancer. The majority, accounting for 99.69%, did not have cervical cancer. These results highlight the importance of pap smear screenings as a valuable tool for early detection and prevention of cervical cancer. They also highlight the importance of regular screenings, especially for younger women, to detect and treat cervical abnormalities at an early stage.

Little information exists regarding high-risk human papillomavirus (HPV) subtypes in human immunodeficiency virus (HIV) patients with atypical squamous cells of undetermined significance (ASCUS) cytologic results. This study aimed to characterize further HPV prevalence and high-grade cervical intraepithelial neoplasia (CIN) in this sub-population of patients. This is a secondary analysis of a prospective HPV natural history study involving 200 HIV-sero-positive patients. We analyzed 102 patients from this cohort with a cervical cytologic diagnosis of ASCUS for high-risk and low-risk HPV prevalence, clearance of HPV infection, progression or regression of cervical cytologic abnormality, and prevalence of CIN 2 or worse at the time of indicated colposcopy. Pap smears were slide-based and HPV testing was performed using nested polymerase chain reaction. Overall prevalence of ASCUS in the HIV population was 20% (40 of 200 patients). Despite a high prevalence of all HPV subtypes (74 of 102 subtypes; 73%), high-risk subtypes were present in only 32% of patients (33 of 102 patients) with ASCUS cytologic results. In 5 of 42 patients (12%) undergoing colposcopy within 6 months of ASCUS cytologic results, CIN 2 or worse was found. Sensitivity, specificity, positive predictive value, and negative predictive value of a high-risk or intermediate-risk HPV test for CIN 2,3 were 100%, 70%, 31%, and 100%, respectively. Progression to high-grade intraepithelial lesion cytologic results after ASCUS was rare (5/64 evaluable patients; 8%) but persistence of low-grade cytologic results (ASCUS or low-grade intraepithelial lesion) was common (43/64 evaluable patients; 67%). Despite a high rate of HPV infection in the HIV population with ASCUS Pap results, high-risk HPV subtypes represent a minority of patients and are significantly associated with presence of high-grade CIN at colposcopy. High-risk HPV testing should be investigated further in the HIV population.

The human papillomavirus (HPV) plays an important role in the progression of cervical carcinoma. High-risk (HR) HPV types have been mainly identified in cytologic high-grade squamous intraepithelial lesions (HSILs) and histologic invasive carcinoma of the cervix. We examined cervical swabs of patients with abnormal Papanicolaou (Pap) smears, diagnosed as low-grade squamous intraepithelial lesions (LSILs) including atypical squamous cells of uncertain significance or HSILs. Low-risk (LR) HPV and HR-HPV types were identified by the Digene Hybrid Capture II test. Two-dimensional (2D) gel electrophoresis was used to specify the physical state of HPV DNA sequences. Expression of E6/E7 messenger RNA (mRNA) transcripts was analyzed by reverse transcriptase-polymerase chain reaction. Histopathologic results were correlated to the patients' physical status and HPV DNA mRNA transcripts. Pap smears with HPV infections of LR and HR types were correlated to the degree of squamous intraepithelial lesions (SILs). Comparing the physical states of HPV DNA sequences with the expression of HPV E6/E7 mRNA transcripts, all types were identified only as extrachromosomal in benign cervical smears, cervical intraepithelial neoplasia (CIN) I and II. HPV16 showed all physical states in CIN III/carcinoma in situ (CIS), whereas HPV18 only existed in mixed and integrated forms. HPV31/33/52b/58 appeared in all stages of lesions most commonly in extrachromosomal form; in integrated form, they were present only in CIN III/CIS. Although integration of some HR-HPV types is not always necessary for progression of SILs, the above-mentioned method is useful to analyze the physical state of HPV DNA sequences and predict the progression of SILs.

Background Immunocytochemical staining for overexpression of the cell-cycle regulatory protein p16INK4a has been shown to be an efficient approach to triage to colposcopy women with cervical smears categorized as Atypical Squamous Cells (ASC). Overexpression of p16 is associated with the transforming activity of the HR-HPV-E7 oncoprotein in cervical dysplasia. Ki-67 is a marker of cell proliferation of dysplastic epithelium. The efficiency of p16 and Ki-67 separately has been widely described. In high-grade squamous intraepithelial lesion (H-SIL) and cancer they can be co-expressed and the identification of cells with double staining reactivity (p16/Ki-67) can be used as an indicator of H-SIL. We aim to evaluate the diagnostic performance of double p16/Ki-67 staining in the detection of underlying H-SIL in cytological smears of women referred to colposcopy due to an ASC cervical smear result. Design Prospective diagnostic test study. It took 18 months to complete the representative number of cases considering the prevalence of ASC in the colposcopy consultation. Samples were included from patients referred to colposcopy with a cytological diagnosis of ASC. Liquid based cytology was taken and processed to obtain a blank cytological preparation. The p16/Ki-67 staining was performed using CINtec Plus™. The immunoreactivity for both markers evidenced by one or more cervical epithelial cells with brown cytoplasmic immunostaining for p16, and nuclear red for Ki-67, was evaluated by two pathologists blind to colposcopy or biopsy results. Biopsies and/or endocervical curettage were obtained when the colposcopist considered necessary and they were considered as gold standard. In cases where there was no visible lesion and no biopsy was taken, colposcopy was considered gold standard and it was classified as: satisfactory/unsatisfactory, negative/normal or positive/abnormal. A high-grade biopsy lesion (≥ CIN2) with H&amp;E was considered as a final diagnosis. Results There were 120 cases included of ASC (114 ASCUS and 6 ASC-H), from women between 18 and 82 years (mean=38.6). 90 (75.0%) cases had histological study: 62 (68.9%) biopsies and 28 (31.1%) endocervical curettages, of which 17 (14.28%) cases had ≥CIN2, and none were cases of invasive cancer. p16/Ki-67 staining was positive in 21 (17.5%) cases, (64.7% sensitivity for ≥CIN2). All the ASC-H cases (3, 100%), and 57.1% of ASCUS cases with ≥CIN2 as final diagnosis were positive to p16/Ki-67. The specificity of p16/Ki-67 dual staining was greater than 90%. Conclusions There was a p16/Ki-67 specificity that exceeded the values ​​published in other studies on this double staining, but, the positivity and sensitivity estimates were lower than reported previously. The variability of p16/Ki-67 staining in HSILs would reflect the heterogeneity of these lesions. Citation Format: Lia Barrios, Luis Alvis, Ines Benedetti. Simultaneous p16/ki-67 expression in detection of high-grade squamous intraepithelial lesions, in women with ASC in cervical smears [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1123.

Recently, practice guideline for the early detection of cervical cancer in Korea has been released in this journal [1].It was developed based on preexisting guidelines generated by the American Society for Colposcopy and Cervical Pathology (ASCCP) [2], the National Comprehensive Cancer Network [3], the United States Preventive Services Task Force [4], and the Institute for Clinical Systems Improvement [5].Coincidentally, updated versions of ASCCP guideline [6] and American Cancer Society (ACS) guideline [7] have been issued around the same time.Therefore, the updated contents of the abovementioned guidelines are not reflected in ours.The essential changes of the 2012 ASCCP guidelines from prior 2006 version are as follows [6]: 1) cytology reported as negative but lacking endocervical cells can be managed without any repeat, 2) cytology reported as unsatisfactory requires repeat even if human papillomavirus (HPV) is negative, 3) For atypical squamous cells of undetermined significance (ASC-US) cytology, immediate colposcopy is not an option.The serial cytology option for ASC-US incorporates cytology at 12 months, and then if negative, cytology every 3 years, 4) ASC-US and HPVnegative results should be followed with co-testing at 3 years rather than 5 years, 5) ASC-US and HPV-negative results are insufficient to allow exit from screening at age 65 years, 6) women aged 21-24 years are managed conservatively.Recently reported rates of cytology results reported as negative but lacking endocervical cells have ranged from 10% to 20% [8].Prior guidelines recommended early repeat cytology [9].A recent meta-analysis found that negative cytology had favorable specificity and negative predictive value despite absent endocervical cell component [10].Given that most cytology is performed using liquid-based media, unsatisfactory cytology results arise mainly from insufficient squamous cells [11].The 2012 ASCCP guidelines recommended repeat cytology in 2 to 4 months for women with an unsatisfactory cytology result.Those two issues regarding specimen adequacy were not included in our guidelines.The management of women with ASC-US has also been

The Bethesda Pap Smear system and its 1991 revisions aim to simplify Papanicolaou (Pap) smear reporting and make it more reproducible. It redefines the Pap smear request as a medical consultation. The pathologist consultant is required not only to provide the smear reading but also its clinical recommendation. The Bethesda system insists on a detailed Pap smear report assessing specimen adequacy and types of epithelial changes. Squamous cell abnormalities are grouped according to their biologic potential. Both cervical intraepithelial neoplasia, grade I (CIN I) (mild dysplasia) and human papillomavirus (HPV) lesions are grouped together as low-grade squamous intraepithelial lesions (LGSIL), while moderate and severe dysplasia (CIN II and III) belong to the high-grade squamous intraepithelial lesion (HGSIL) category. Atypical squamous cells of undetermined significance (ASCUS) and atypical glandular cells of undetermined significance (AGCUS) need further qualification as to whether they favor either a reactive or neoplastic process. Guidelines for management of abnormal Pap smears are discussed in detail. Semin. Surg. Oncol. 16:217–221, 1999. © 1999 Wiley-Liss, Inc.