Negative For Intraepithelial Lesion Or Malignancy Research Articles

Atypical squamous cells of undetermined significance cervical cytology in Bahrain: Reporting rates, high-risk HPV testing, and cytologic and histopathologic follow-up findings.

Atypical squamous cells of undetermined significance cytology (ASC-US) is a challenging and equivocal diagnosis for pathologists in cervical Pap smears. The data on ASC-US cervical cytology in Bahrain are deficient. This study reviewed and identified the reporting rates, high-risk human papillomavirus (HPV) testing results, histopathologic follow-up findings, and the cytologic progression of patients diagnosed with ASC-US in Bahrain. A retrospective chart review was conducted on the medical records of 23,888 women who had Pap smear test results between January 2019 and March 2022 at the main referral tertiary hospital in Bahrain to identify the ASC-US cases. High-risk HPV (hrHPV) genotype was identified, and the histopathological results of the cervical biopsy was recorded. In addition, cytologic follow-up Pap smear tests conducted within 1 year of ASC-US diagnosis were tracked to monitor the progression or regression of ASC-US. In this study, 259 out of 23,888 women reported to have ASC-UC cytology results with a reporting rate of 1.1%. The mean age of the ASC-US cases was 43 ± 11.6. Thirty percent of the ASC-US cases tested positive for hrHPV, and they were predominantly infected with the other hrHPV genotype (75%). When the histopathological changes of the cervix were analyzed, 82.1% had normal histopathologic findings. However, low-grade cervical intraepithelial neoplasia-1 was reported in 2 cases (7.1%), and high-grade cervical lesions (cervical intraepithelial neoplasia-2 and higher) were reported in 3 cases (10.7%). Regarding the cytologic follow-up, most of the ASC-US cases were negative for intraepithelial lesion or malignancy (NILM) (73.8%) or had persistent ASC-US (17.9%). The remaining minority of cases progressed into either low-grade squamous intraepithelial lesions (6%) or high-grade squamous intraepithelial lesions (2.4%). There was a statistically significant and relatively strong association between the cytology follow-up findings and the hrHPV test results (χ2 [2] = 8.869, P < 0.012, Cramer's V = 0.417). This is the first and largest study to characterize the ASC-US cytology cases in Bahrain. The reporting rates of ASC-US fell within the worldwide reported range. Although most of the ASC-US cases regressed into NILM, ASC-US showed progression into more advanced cervical cytologic diagnoses or contributed to the malignant transformation of cervical tissue, especially in the presence of hrHPV infection which was positive in 30% of the ASC-US cases. This emphasizes the role of cotesting (combination of hrHPV genotyping and Pap smear test) and the importance of colposcopic evaluation of those women with cytologic follow-up tests at 1 year of diagnosis. Implementing these recommendations in the cervical cancer screening practice in Bahrain will help in having a better management plan for women diagnosed with ASC-US cervical cytology.

High-grade cervical lesions diagnosed by JAM3/PAX1 methylation in high-risk human papillomavirus-infected patients.

Currently, traditional cervical cancer screening methods, such as high-risk human papillomavirus testing and liquid based cytology (LBC), still possess limitations. This study aims to identify new diagnostic biomarkers to achieve the goal of "precision screening" via exploring the clinical value of DNA methylation [ΔCtP: paired box gene 1 (PAX1)and ΔCtJ: junctional adhesion molecule 3 (JAM3)] detection in cervical exfoliated cells for the diagnosis of high-grade cervical lesions. A total of 136 patients who underwent gynecological examinations in the vaginal room of the Department of Gynecology at the Third Xiangya Hospital of Central South University from June 2021 to June 2022 were retrospectively studied. Among them, 122 patients had non-high-grade cervical lesions, and 14 patients had high-grade cervical lesions. The variables included general information (age, body mass index, and menopause status), LBC, high-risk human papillomavirus, cervical tissue pathology, vaginal examination results, and the ΔCt values of JAM3 and PAX1 gene methylation. Logistic regression analysis was used to identify the factors affecting the diagnosis of high-grade cervical lesions, followed by correlation analysis and construction of a conditional inference tree model. Logistic regression analysis showed that the methylation ΔCt values of PAX1 and JAM3 genes and LBC detection results were statistically significant between the high-grade cervical lesions group and the non-high-grade cervical lesions group (all P<0.05). Correlation analysis revealed a negative correlation between cervical pathological changes and ΔCtP (r=-0.36, P<0.001), ΔCtJ (r=-0.448, P<0.001), LBC (r=-0.305, P<0.001), or bacterial diversity (r=-0.183, P=0.037). The conditional inference tree showed that when ΔCtJ>10.13, all of patients had non-high-grade cervical lesions, while ΔCtP>6.22, the number of non-high-grade lesions accounted for 97.5% (117/120), and high-grade lesions accounted for only 2.5% (3/120). When ΔCtJ>8.61 and LBC were atypical squamous cell of undetermined significance or negative for intraepithelial lesions or malignancy (NILM), 105 (99.1%) patients were non-high-grade cervical lesions, only 1 (0.9%) patient was high-grade lesion. When the results of LBC were high-grade lesions, only 9 patients' histopathological examination was the high-grade lesions and 3 non-high-grade lesions. When LBC indicated low-grade lesions, atypical squamous cell of undetermined significance, no intraepithelial lesions, and ΔCtP>6.22, 117 (97.5%) of patients' histopathological examination was the non-high-grade lesions. The JAM3/PAX1 gene methylation test can be used independently for the stratified diagnosis of high-grade/non-high-grade cervical lesions in women with high-risk human papillomavirus infection, independent of the cytological results of cervical excision. The JAM3/PAX1 gene methylation test can also be used in combination with LBC to make up for the shortcomings of low sensitivity of LBC. In addition, the application of methylation kit in large-scale cervical cancer screening in the future will be good to the detection of more patients with high-grade cervical lesions, and achieve early screening and early treatment for cervical lesions/cancer.

Cytomorphological study of pap smear and its efficacy to detect various cervical lesions

: Cervical lesions require screening for early diagnosis to differentiate between non-neoplastic and neoplastic lesions of cervix. The present research aimed to evaluate the prevalence of various cervical lesions and detect the efficacy as a screening test of pap smear for early diagnosis of cervical lesions. : The current retrospective study was conducted in the Department of Pathology, SSMC, Rewa, M.P. Total 658 cervical pap smears were retrieved, re-examined and re-classified according to the revised Bethesda system for reporting of cervical cytology, 2014. Out of 658 pap smears, 234 biopsies were available, which were re-examined histopathologically and correlation was done with their corresponding cytological findings.: Out of 658 pap smears, negative for intraepithelial lesion or malignancy (NILM) was found in 74.47% smears, while the prevalence of epithelial cell abnormalities (ECA) was 24.32%. Amongst ECA, most common (11.86%) cervical lesion was low-grade squamous intraepithelial lesion (LSIL). Diagnostic sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy for the diagnosis of pre-invasive and invasive cervical lesions was found 70.54%, 81.9%, 82.72%, 69.35% and 75.6% respectively.: The current study showed that pap smear cytology is able to detect various cervical lesions with a diagnostic accuracy of 75.6%. So, women belonging to reproductive or postmenopausal age-group should be routinely screened for cervical lesions by non-invasive pap smear method. Conclusively, early diagnosis of cervical lesions is possible, thus reducing the incidence of invasive cervical carcinoma.

Searching for new early detection markers of oral epithelial dysplasia and oral squamous cell carcinoma using oral liquid-based cytology

ObjectiveOral squamous cell carcinomas (SCCs) arise from oral potentially malignant disorders (OPMDs), including oral epithelial dysplasia (OED); however, useful detections markers for early detection of OED and oral SCC are lacking. In this study, we aimed to evaluate the sequential mRNA and protein expression patterns of BRD4, c-MYC, TP53, and MUC21 in human oral samples by liquid-based cytology (LBC) and determine whether these markers are useful for early detection of OED and oral SCC when combined with oral cytological screening. MethodsA total 200 patients were obtained from our hospital between 2020 and 2022. These are samples from same cases with oral cytology and corresponding histological diagnosis. The expression of these markers was examined by immunocytochemistry and mRNA analysis. The percentages of cells with nuclear or cytoplasmic immunostaining were calculated using the labeling index (LI). BRD4, c-MYC, and TP53 mRNA expression levels were upregulated in tissue during progression from a status of negative for intraepithelial lesions or malignancy (NILM) to positive for SCC. BRD4-LI and c-MYC-LI significantly increased in low-grade squamous intraepithelial lesions (LSIL), high-grade squamous intraepithelial lesions (HSIL) and SCC samples, whereas the expression of MUC21 mRNA and MUC21-LI gradually decreased. TP53-LI increased only in SCC samples. ConclusionsWe conclude that monitoring BRD4 and c-MYC expression with immunocytochemistry could improve the early detection of OED and oral SCC.

Do women with high-risk HPV E6/E7 mRNA test positivity and NILM cytology need colposcopy?

PurposeThis study aimed to assess the value of an HPV E6/E7 mRNA assay and HPV 16 18/45 genotype assay combined with age stratification for triaging women negative for intraepithelial lesions or malignancy (NILM) cytology.MethodsFrom January 2017 to December 2021, a total of 162,309 eligible women underwent cervical cancer screening at the Affiliated Hospital of Jining Medical University, China. Excluding those with negative HPV E6/E7 mRNA, abnormal and unsatisfactory cytology, and those who failed to undergo colposcopy, 6,845 women were ultimately included in our study. We analysed the triage guidance for different subtypes of HPV in the presence of NILM cytology.ResultsAmong 162,309 women, 19,834 (12.2%) were positive for HPV E6/E7 mRNA. Of the 6,845 women included in the study, 1,941 (28.4%), 561 (8.2%), 55 (0.8%) and 4,288 (62.6%) tested positive for HPV 16, HPV 18/45, HPV16/18/45 or other HR-HPV genotypes, respectively. The proportions of LSIL+ (including LSIL, HSIL and ICC) and HSIL+ (including HSIL and ICC) pathological results in the HPV 16/18/45 + group were 57% and 34.1%, respectively, higher than 36.3% and 11% in the other HR-HPV + group (χ2 = 653.214, P < 0.001). The percentages of LSIL + and HSIL + in the HPV16 + group (61.3% and 42.8%, respectively) and HPV16+/18/45 + group (76.3% and 41.9%, respectively) were much higher than those in the HPV18 + group (40.6% and 13.1%, respectively) (P < 0.001). However, there was no significant difference in the percentage of histopathological results between the HPV16 + group and HPV16+/18/45 + groups (P > 0.05). The above results were consistent after stratification according to age.ConclusionThe rate of histopathological abnormalities was still high for the other HR-HPV subtypes with NILM cytology, although the rate of histopathological abnormalities was much higher for the HPV 16/18/45 positive subtypes. Therefore, colposcopy should be performed in women with HPV E6/E7 mRNA positivity and NILM cytology, regardless of age and HPV genotype.

Are HPV-negative lesions concerned for the introduction of primary HPV testing for cervical cancer screening in Japan?

In Japan, primary human papilloma virus (HPV) testing has not been introduced for cervical cancer screening due to concerns that HPV-negative lesions may be missed and a lack of Japanese data. The purpose of this study was to evaluate the validity of primary HPV testing in Japan by analyzing cervical intraepithelial neoplasia 2 (CIN2) or more/high-risk HPV- (CIN2+/hrHPV-) cases in cervical cancer screening. Data from 35 525 cervical cancer screenings with HPV testing and cervical cytology from 2011 to 2019 in Saga City, Japan, were reviewed. The cases with low-grade squamous intraepithelial lesion (LSIL+)/hrHPV- were analyzed in detail. The results of the 35 525 examinees were as follows: 31 123 were negative for intraepithelial lesion or malignancy (NILM)/hrHPV-, 2612 were NILM/hrHPV+, 262 were atypical squamous cells of undetermined significance (ASC-US)/hrHPV-, 213 were ASC-US/hrHPV+, 291 were LSIL+/hrHPV-, and 1024 were LSIL+/hrHPV+. Of the 256 LSIL+/hrHPV- examinees for whom histology was available, CIN2+ were CIN2 9.4% (24/256), CIN3 3.9% (10/256), cervical adenocarcinoma 0.4% (1/256), uterine corpus cancer 1.2% (3/256), and uterine sarcoma 0.4% (1/256). Overall, the rate of LSIL+/hrHPV- was 0.82% (291/35.525), 0.1% (36/35525) of which were cervical lesions with CIN2+. Only one cervical adenocarcinoma was detected, but gastric-type adenocarcinoma was not included. HPV-negative CIN2+ or cervical adenocarcinoma is not a concern for the introduction of primary HPV screening in Japan. Primary HPV testing in cervical cancer screening is considered a feasible method that can be used in Japan, although an algorithm suitable for Japan and a national-level management system need to be established.

Programmed death-ligand 1 (PD-L1) expression in cervical intraepithelial neoplasia and cervical squamous cell carcinoma of HIV-infected and non-infected patients

Programmed death-ligand 1 (PD-L1) is overexpressed in cervical carcinoma, hindering tumor destruction. The aim of this study was to assess PD-L1 expression by immunohistochemistry in cervical squamous cell carcinoma (SCC) and squamous intraepithelial lesions (SILs) from human immunodeficiency virus–positive (HIV+) and human immunodeficiency virus-negative (HIV-) patients. A total of 166 SCC and SIL samples of HIV+ and HIV- patients were included and analyzed for PD-L1 expression through tumor proportion score (TPS), and results were stratified in five TPS groups using SP263 antibody and, combined positive score (CPS) using 22C3 antibody. In cohort 1 (SP263 clone), all HIV+ patients were negative for intraepithelial lesion or malignancy (NILM), and low-grade squamous intraepithelial lesions (LSILs) scored < 1; and 87.5% of high-grade squamous intraepithelial lesions (HSILs) adjacent to SCC, 19% of HSILs non-adjacent to SCC, and 69% of SCCs scored ≥ 1 (15.4% scored 5). In HIV- patients, all NILM, LSILs, HSILs adjacent to SCC, and two HSILs non-adjacent to SCC scored < 1. SCC: 88.2% scored ≥ 1 and 5.9% scored 5. In cohort 2 (SP263 and 22C3 clones), 16.7% of HIV+ patients with SCC were positive with both clones, CPS ≥ 1 (22C3) or score 5 (≥ 50%) (SP263), showing no significant differences in positivity between both clones. These results indicate that a relatively low percentage of SCCs (16.7%; both in HIV+ and in HIV- patients) express PD-L1 (TPS ≥ 50% and CPS > 1), which may be due to some samples being archival material, sample characteristics, or use of different methodologies, highlighting the need for standardization of PD-L1 assessment in SCC of the cervix. The fact that PD-L1 is overexpressed in SILs of HIV+ patients suggests potential additional applications for immunotherapy in this disease.

An Alarming Evidence Of Increased HPV Infection In Cervical Smear In Iraqi Patients

Background: Cervical cancer is one of the common cancers among women worldwide, with increasing incidence. This study was designed to assess the role of cervical cytology in detecting the various cervical lesions predisposed to cervical cancer with the special emphasis on squamous intraepithelial lesions (SIL) and to predict the prevalence of these lesions and their association with Human papilloma virus (HPV). Patients and methods: This study enrolled 3500 women aged 17 years and above, presented with cervical lesions and attended for cytological evaluation of cervical smears. The data was retrieved from the archives of these patients for the period from January 2017 to December 2021.  All results were classified according to Bethesda system (2014) and statistically analyzed. Results:  the cytological examinations revealed that 91.7% of the submitted cases were negative for intraepithelial lesion or malignancy (NILM). Abnormal cellular changes were reported in 8.3% of the cases; Low-grade squamous intraepithelial lesion was the most common abnormality representing 4.7%, while High-grade squamous intraepithelial lesion constituted 0.5% of the total cases. A HPV-DNA test was done to 220 cases; 52 cases (23.6%) were positive, most of them (73%) were of low-risk genotypes while high risk genotypes were reported in 27% of the cases. Conclusion: the cervical squamous abnormality has formed a low prevalence rate while HPV-DNA test has been detected in a considerable proportion of Iraqi patients. This fact discloses alarming evidence of a growing problem in the population that needs to introduce a screening program for early diagnosis of precancerous cervical lesions.

A retrospective study on cervical cancer screening- In a newly opened tertiary care Centre in Eastern India

: One of the most prevalent cancers, cervical cancer is also the leading cause of mortality for women in underdeveloped nations. A fundamental test for finding infections and precancerous diseases is the Papanicolaou smear. This study aims to comprehend the function of cervical screening in detecting premalignant, malignant, and non-neoplastic lesions as well as the prevalence of different lesions in women who received a traditional pap smear technique. We screened women in the age group of 15-70 years who attended the Outpatient department of the Obstetrics and Gynaecology department of AIIMS, Kalyani. All women who gave consent for screening by Pap smear test were included. Of 2133 cases, most of the cases were benign comprising of Negative for Intraepithelial Lesion or malignancy (NILM) of about 1989 (93.24%) cases, 705 (33.05%) inflammatory. Atypical squamous cells of undetermined significance in 44 cases (2.06%), Atypical squamous cells cannot exclude HSIL in 3 (0.14%), low-grade squamous intraepithelial lesion (LSIL) in 11 (0.52%), high-grade squamous intraepithelial lesion (HSIL) in 5 (0.23%) women and Atypical glandular cell in 7 (0.33%). Out of 202 asymptomatic women (9.47%), 12 cases (0.56%) showed epithelial cell abnormality (8 ASCUS, 2 LSIL, 1 ASCH, 1HSIL) (Odds ratio=0.5056, Significance level, P=0.0362). Conventional Pap smear test is a very easy and cheap diagnostic tool to detect premalignant, malignant, and non-neoplastic lesions and the prevalence of various lesions.  As per the American Cancer Society (ACS), a pap smear should start from 25 years to be done till 65 years (repeated after every 3 years).

Endocervical curettage for diagnosing high-grade squamous intraepithelial lesions or worse in women with type 3 transformation zone lesions: a retrospective, observational study

BackgroundThis study aimed to assess the value of endocervical curettage (ECC) in detecting high-grade squamous intraepithelial lesion or worse (HSIL+) in women with type 3 transformation zone (TZ3) lesions, and to identify the clinical characteristics of patients with TZ3 lesions who benefit most from ECC.MethodsThis retrospective, multicenter study included 1,905 women with TZ3 lesions who attended cervical screening in one of seven tertiary hospitals in China between January 2020 and November 2021. All participants had received abnormal results and had been referred to colposcopy. Risk factors were identified through univariate and multifactorial logistic analyses.ResultsIn total, 20.5% (n = 391) of HSIL+ cases with TZ3 lesions had been diagnosed with biopsy and ECC. ECC detected 0.8% (n = 15) HSIL+ cases otherwise missed by biopsy alone. Multivariate analysis identified four factors which influenced detection performance. The probability of detecting HSIL+ with ECC is 2.653 (95% confidence interval [CI] 1.009–6.977) times greater in women aged 40–49 years and 2.545 (95% CI 0.965–6.716) times greater for those aged 50 years and older compared to those younger than 30 years. The probability of ASC-H (atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion) and HSIL cytologies were respectively 2.415 (95% CI 1.213–4.808) and 2.933 (95% CI 1.648–5.220) times higher than for NILM (negative for intraepithelial lesion or malignancy). Women with human papillomavirus 16/18 infections were 2.299 (95% CI 0.942–5.613) times more likely to be HSIL+. Precancerous lesions were 35.884 (95% CI 12.214–105.426) times more likely in women who had high-grade colposcopic impressions compared to those with normal impressions.ConclusionsECC should be performed for patients with ASC-H or HSIL cytologies, human papillomavirus 16/18 infections, and for those with high-grade colposcopic impressions. This will increase the number of HSIL+ cases identified using biopsy by reducing the number of false negatives.

Determination of Autophagy in Human Cervicovaginal Smears by Cytological and İmmunocytochemical Methods.

Autophagy is a catabolic process whereby organelles and long-lived proteins are recycled through lysosomes to maintain cellular homeostasis. This process is being widely studied using culture techniques and animal models; however, cervicovaginal smears have not been used to detect autophagy. Our study aims to detect and evaluate autophagy in normal, malignant, infectious, and atypical cells in cervicovaginal smears by using cytological and immunocytochemical methods. Papanicolaou-stained 200 cervicovaginal smears were examined and 55 of 200 (27.5%) smears containing negative for intraepithelial lesion or malignancy (NILM) with identifiable infections and/or reactive/reparative changes (INF); briefly, NILM-INF (n = 31, 56.4%), atypical (n = 4, 7.3%), and malignant cells (n = 20, 36.3%) were evaluated as a study group. One hundred forty-five of 200 (72.5%) normal smears were accepted as the NILM without any identifiable infections (control group). The autophagy marker protein Microtubule-associated protein 1 light chain 3 A (MAP1LC3A) was used for immunocytochemical examination. The staining intensity of the MAP1LC3A protein and autophagy positivity were lower in the malignant cells; however, they were higher in the NILM-INF and atypical cells. A statistically significant correlation between the malignant and normal cells was obtained for the autophagy positivity (P = 0.012). In view of the staining intensity of MAP1LC3A protein by the H-score method, a significant correlation was found between the NILM-INF and the normal cells (P = 0.015). Autophagy was detected in various cervicovaginal smears for the first time in this study. Our findings indicate that an autophagy process is essential in infectious cells as well as in the transformation of atypical cells into malignant cells in carcinogenesis.

Cervical Cytology and Histology Correlation as an Analytic Quality Assurance Exercise: Experience from an Accredited Cytology Laboratory.

The performance parameters of cervical cytology in any accredited cytology laboratory requires implementation of quality control exercise, which ensures acceptable performance by a laboratory. This study aims to assess the analytical aspect of quality control measures by evaluating the frequency and accuracy of epithelial abnormalities as detected in cervical Pap smears using histopathologic diagnosis as the gold standard. A retrospective diagnostic test study from 2018 to 2020 was conducted. Out of the total 6000 Pap smears, histopathologic correlation was available in 150 cases in the form of colposcopic-directed biopsy (CDB) and loop electrosurgical excision procedure (LEEP) tissue in 105 cases. The quality control measures analyzed were Atypical Squamous Cell: Squamous Intraepithelial Lesion (ASC: SIL) ratio, cyto-histo correlation, and study parameters like sensitivity, specificity, positive predictive value, and negative predictive value of Pap smears as against CDB and LEEP. 4.5% smears were reported as inadequate, 92.3% as Negative for intraepithelial lesion or malignancy (NILM), followed by epithelial abnormality found in 3.21%. The ASC: SIL ratio was 1.3:1. Concordance rate against CDB was 100% in Squamous cell carcinoma (SCC), 82.35% in high-grade squamous intraepithelial lesion (HSIL), 82% in atypical squamous cells of undetermined significance (ASCUS), 65.6% in low-grade squamous intraepithelial lesion (LSIL), and 50% in Atypical Squamous Cell ,High grade Squamous Intraepithelial Lesion can not be ruled out (ASC-H). Total concordance rate was 84.15%. Sensitivity of Pap smear was 65% for LSIL and 82% for HSIL. Specificity, positive predictive value, and negative predictive value were 63.63%, 90%, and 75%, respectively. Concordance rate was 96% with LEEP. Quality control measures give an insight of performance of any accredited cytology laboratory. This exercise needs to be conducted on a regular basis, so that relevant steps can be taken in case of major discrepancy.

COLPOSCOPIC EVALUATION OF POST-MENOPAUSAL WOMEN WITH NORMAL CERVICAL CYTOLOGY

1. Introduction The most common genital cancer seen in Indian women is Carcinomacervix Its incidence is approximately 1 in 53 Indian women during their lifetime compared to 1 in 100 in developed countries. In women ≥ 50 years where the lifetime risk of cervix cancer is estimated as 3.5%, which can be reduced to 0.8% with screening. Pap smear evaluation alone is inadequate for predicting the precancerous lesions in postmenopausal women due to hypoestrogenic changes of menopause which makes it difcult to differentiate atrophic cellular changes from other pathologic conditions, giving more false negative results which can be reduced if combines with colposcopy examination and guided biopsy wherever needed 2. Aim &amp; Objective To diagnose intraepithelial lesions in postmenopausal patients with normal cytological ndings and to assess the usefulness of cytological screening, colposcopy, and colposcopy-directed biopsy in these patients. 3. Material And Method- A retrospective study was carried out from 1st January 2018 to 31 October 2022 at a colposcopy clinic, in district Shivpuri M.P. on 104 post-menopausal females of age group 45-68 years. After detailed history and examination, a pap smear in all 104 patients was taken. All patients with negative cytology reports for Intra epithelial lesions with persistent symptoms and suspicious signs were subjected to colposcopy. 23 Patients with positive Colposcopic ndings were subjected to Colposcopic guided biopsy. histopathological evaluation was done. 4. Result This study analyzed 104 postmenopausal patients who had Pap smear reports with NILM (Negative for intraepithelial Lesion or Malignancy). 58% of the patients were referred by other Doctors. The most common post-menopausal age group nd in this study was between 45-55 (52.88%), Most of the patients were of a low socioeconomic group (54.81%), Multipara (3-5 parity 66.35%). with a history of menopause of 5-10 years (49.04%) duration. Only 5.77% of patients had 3 Pap smear reports with them, and a history of smoking was present in 6.73% of cases. The most common presenting symptom was discharge PV (47.11%) followed by Foul smelling bloody discharge (14.42%). Post-coital bleeding (12.5%), Post-menopausal bleeding (8.65%), and dyspareunia (4.80%). On colposcopy, (77.89%) of cases had normal Colposcopic ndings while (22.11%) had abnormal Colposcopy ndings. In 17.30% of cases, LSIL was suspected, in 4.80% of cases HSIL was suspected on colposcopy Colposcopy-guided biopsy was done in 23 (22.11%) patients with suspected CIN. On histopathology 9.61% of cases were positive for intraepithelial lesions, CIN1 was found in 7.69%, and CIN2 in 1.92%. Carcinoma in situ and Invasive carcinoma were not found in any case. 10(9.61%) out of 104 patients had cervical intraepithelial neoplasia diagnosed on colposcopy-guided biopsy and histopathology report. 5. Conclusion- In our study, despite the Pap smear report as NILM (Negative for intraepithelial lesion or malignancy). ,10(9.61%) out of 104patients had cervical intraepithelial neoplasia diagnosed on colposcopy guided biopsy, thus we recommend, the combined use of cervix cytology, colposcopy, and histopathology in postmenopausal cervix cancer screening evaluation to improve the diagnosis of the cervical intraepithelial lesion.

Clinical history of female-to-male transgender patients is needed to avoid misinterpretation of cervical Papanicolaou tests.

Cervical cancer screening is as important in female-to-male transgender (FTMT) patients as it is in cisgender female patients. The aim of this study was to examine the impact of clinical information regarding gender identity and testosterone therapy on the cytological interpretations. A list of FTMT patients and cisgender female patients who had received a cervical Papanicolaou (Pap) test for cancer screening was obtained. The cytological diagnoses, rendered at the time of collection, were recorded. A retrospective slide review with knowledge of the pertinent clinical information, including testosterone therapy status, was performed. The data sets were statistically compared. Of 122 cervical Pap tests in 111 FTMT individuals, 23 (19%) had surgical follow-ups; 73 (60%) had HPV testing, of which 12 (16%) were positive for high-risk strains; and 79 (65%) were known to be receiving testosterone. On the "original" review, 12 (9.8%) tests were diagnosed as unsatisfactory. Seventy-one (58%) Pap tests were initially diagnosed as negative for intraepithelial lesion or malignancy (NILM) without atrophy and 32 (26%) with atrophy. Seven (5.7%) of the tests were initially diagnosed as abnormal. On the "retrospective" review, the rate of unsatisfactory tests remained the same, and atrophy was observed in 76 (62%) tests. The number of abnormal tests was reduced to 4 (3.3%) after the retrospective review. Almost all comparative studies returned a P-value of ≤0.05. Our findings indicate that clinical information regarding whether a subject is transgender and/or is receiving testosterone therapy is crucial to avoiding Pap test overcalls.

Evaluation of the Cytonucleomorphometric Parameters for Cases Diagnosed as Squamous Cell Abnormality on Conventional Cervico-Vaginal Pap Smears.

The natural history of cervical cancer is unique that it is preceded by a precancerous condition for a long time. Morphometry as a tool can be used in early and accurate diagnosis of these precancerous and cancerous lesions. The present study aims at assessing the utility of cellular and nuclear morphometry in differentiating squamous cell abnormality from benign conditions and also differentiating the categories of squamous cell abnormalities. Forty-eight diagnosed cases of squamous epithelial cell abnormality, that is, 10 cases each of atypical squamous cell of undetermined significance (ASC-US), low-grade squamous intraepithelial lesion (LSIL), high-grade SIL (HSIL), and squamous cell carcinoma (SCC) and eight cases of ASC-H (ASC cannot exclude HSIL), were made the sample population and compared with a control population of 10 cases of negative for intraepithelial lesion or malignancy (NILM). Parameters like nuclear area (NA), nuclear perimeter (NP), nuclear diameter (ND), nuclear compactness (NC), cellular area (CA), cellular diameter (CD), cellular perimeter (CP), and nucleocytoplasmic (N/C) ratio were used. There was a significant difference in the six groups of squamous cell abnormality based on NA, NP, ND, CA, CP, and CD (P < 0.05) using one-way analysis of variance. Nuclear morphometry parameters like NA, NP, and ND were found to be the maximum for HSIL, followed by LSIL, ASC-H, ASC-US, SCC, and NILM groups in decreasing order. The mean CA, CP, and CD were found to be the maximum for NILM, followed by LSIL, ASC-US, HSIL, ASC-H, and SCC in decreasing order. On post hoc analysis, the lesions can be divided into three groups: NILM/normal; ASC-US and LSIL; and ASC-H, HSIL, and SCC, based on N/C ratio. In cervical lesions, holistic parameter of cytonucleomorphometry should be taken rather than taking nuclear morphometry only. N/C ratio is a highly statistically significant parameter that can differentiate between low-grade lesions and high-grade lesions.

A Comparison of Conventional Pap Smear and Liquid-Based Cytology for Cervical Cancer Screening.

Early diagnosis and treatment of preinvasive lesions have made cervical cytology one of the most effective methods of cancer screening in industrialized nations, which have seen a sharp decline in the incidence and death of invasive cancer. The aim of this study is to compare liquid-based cytology (LBC) and conventional Pap on cervical smears. From July 2018 to June 2022, 600 patients were included in this cross-sectional study, which was done at the Pathology Department of a Tertiary Care Facility in Western Maharashtra. Of the 600 patients, 570 (95%) had good conventional Pap smear (CPS), whereas 30 (5%) had poor ones. Five hundred and ninety-two (98.6%) LBC smears were satisfactory, whereas 8 (1.4%) were unsatisfactory. Endocervical cells were seen in 294 (49%) CPS, whereas 360 (60%) LBC smears showed endocervical cells. The morphology of inflammatory cells was similar in both techniques. Hemorrhagic background was seen in 212 (35%) CPS and 76 (12.6%) LBC smears. Only two samples showed diathetic background, which was seen on both CPS and smear. Out of the satisfactory smears in the case of CPS, 512 (85%) cases were reported as negative for intraepithelial lesion or malignancy (NILM), whereas 58 (9.7%) cases were reported as epithelial cell abnormality. In LBC smears, 526 (87.3%) were reported as NILM, whereas 66 (11%) were reported as epithelial cell abnormality. Organisms were detected in 208 (34%) CPS and 162 (27%) LBC smears. Screening time was 5 ± 1 min for CPS, whereas it was 3 ± 1 min for LBC smear. Mortality will be decreased using LBC on a bigger scale in nations where many smears can be made and screened in a short amount of time, with the provision of doing human papillomavirus-based testing on the remaining sample.

HPV testing for cervical cancer screening: Should reflex cytology be performed after a positive test for HPV 16 and 18?

At Portuguese-organized cervical cancer (CC) screening programs, all women testing positive for human papillomavirus (HPV) 16 and/or 18 are referred for immediate colposcopy. This study aimed to evaluate the utility of reflex cytology in women who test positive for HPV 16 and/or 18 to improve the efficiency of CC screening.A cross-sectional and retrospective study was performed based on data from the routine CC screening protocol in force at Cova da Beira University Hospital Center, Portugal between August 2012 and June 2021. The screening method was the Cobas 4800 HPV test using the liquid medium Surepath. In all the selected cases, the patient's HPV test results and the cytology and histology findings of the biopsies obtained using colposcopy were analyzed.This study included 339 women who first tested positive for HPV 16 and/or 18 and were referred for immediate colposcopy, in whom 40 (11.8%) cases of high-grade squamous intraepithelial lesion (HSIL+) were diagnosed. Of these, 12 (30%) had reflex cytology negative for intraepithelial lesion or malignancy (NILM) and 14 (35%) had HSIL+ cytology. After 3 years, 14 (9.3%) of the 150 women who were still undergoing follow-up were diagnosed with histologic HSIL+ lesions, of which 5 (35.7%) had baseline NILM cytology.Despite the small sample, the results of this study allow us to conclude that reflex cytology is not useful for discrimination to immediate referral for colposcopy in women who test positive for HPV 16 and/or 18, as most women with a histologic diagnosis of an HSIL+ lesion had <HSIL reflex cytology.

Cytomorphological Variations in Pap Smears amongst Postmenopausal Women Reporting at a Tertiary Care Centre, Tamil Nadu, India

Introduction: In developing countries, cervical cancer is the leading cause of death amongst women. Since women spend one third of their lives in the postmenopausal period, which is most neglected phase, needs a technically simple, non invasive and, cost-effective screening tool for cervical cancer detection and the exact answer is the Pap smear screening test. This simple screening test when performed at regular intervals in post menopausal population, can detect precursor lesions there by reducing cervical cancer morbidity and mortality. Aim: This study was undertaken to evaluate the cytomorphological variations in Pap smears amongst postmenopausal women. Materials and Methods: In this prospective study, a total of 138 satisfactory smears were considered for study amongst 146 postmenopausal women from August 2020 to July 2022 at Bhaarath Medical College and Hospital and then evaluated and categorised based on Bethesda system for reporting cervical cytology 2014. {Reporting elements include specimen type, specimen adequacy, general categorisation, interpretation/result includes general categories of negative for Intraepithelial Lesion or Malignancy (NILM), epithelial cell abnormalities and other malignancies. Results: Out of 138 satisfactory cases, 78.26% (108 cases) 14.5% (20 cases) and 7.24% (10 cases) were diagnosed as of inflammatory/benign conditions, epithelial abnormalities and normal cytology respectively. The mean age for inflammatory/ benign lesions was 57.5 years and majority presenting with postmenopausal bleeding and white discharge. Amongst epithelial abnormalities Atypical Squamous Cells of Undetermined Significance (ASCUS) and Low-grade Squamous Intraepithelial Lesions (LSIL) were commonest. The incidence of ASCUS 7.27% (10 cases), and incidence of LSIL 2.89% (4 cases). The mean age was 57.5 years and majority of patients presented with postmenopausal bleeding and mass per vaginum. Incidence of High grade Squamous Intraepithelial Lesion (HSIL) was 2.17% (3cases), the mean age was 65.5 years and presented with white discharge and postmenopausal bleeding. Incidence of SCC was 2.17% (3 cases) and the mean age was 70.5 years, presented with, postmenopausal bleeding and white discharge. Conclusion: Pap smear is a simple, cheap, safe and gold standard diagnostic tool for screening postmenopausal women for all cervical abnormalities in particular pre-invasive and invasive lesions.

Impact of high-risk Human Papillomavirus genotyping in cervical disease in the Northern region of Portugal: Real-world data from regional cervical cancer screening program.

Cervical cancer prevention is based on primary prevention with vaccines against Human Papillomavirus (HPV) and secondary prevention by screening with High-Risk-HPV (Hr-HPV) detection. Since 2017, cervical cancer screening in women aged 25-60 years has been performed in Portugal using Hr-HPV detection, followed by cytology in Hr-HPV-positive cases.Herein we report the prevalence of Hr-HPV genotypes and cytological abnormalities among 462 401 women (mean age: 43.73 ± 10.79; median age: 45; range: 24-66 years) that participated in the Regional Cervical Cancer Screening Program of the Northern Region of Portugal, performed between August 2016 and December 2021.Overall, we describe a prevalence rate of 12.50% for Hr-HPV varying from 20.76% at age 25% to 8.32% at age 64. The five most common Hr-HPV genotypes identified were HPV-68 (16.09%), HPV-31 (15.30%), HPV-51 (12.96%), HPV-16 (11.06%), and HPV-39 (11.01%). The prevalence of Hr-HPV included in the nonavalent vaccine (HPV-9valent) was 55.00% ranging from 47.78% to 59.18% across different age groups. Considering positive Hr-HPV cases, 65.68% had a Negative for Intraepithelial Lesion or Malignancy (NILM) cytology, 20.83% atypical squamous cells of undetermined significance (ASC-US), 8.85% Low-Grade Squamous Intraepithelial Lesion (LSIL), 1.65% High-Grade Squamous Intraepithelial Lesion (HSIL), 2.85% ASC-H, 0.09% Atypical Glandular Cells, 0.02% Adenocarcinomas, and 0.02% Squamous Cell Carcinoma (SCC). Our analysis revealed that HPV-9val genotypes were responsible for 52.13% NILM, 59.21% ASC-US, 55.06% LSIL, 90.14% HSIL, 83.50% ASC-H, and 100.00% SCC. Furthermore, multiple Hr-HPV infections (risk ratio[RR] = 1.46; 95% confidence interval [CI] 1.34-1.58), HPV-16/18 (RR = 5.16; 95% CI 4.75-5.93), or HPV-9val genotypes (RR = 5.23; 95% CI 4.68-5.85) were associated with a significant risk of developing >  HSIL (p < 0.001).To date, this is the largest study on Hr-HPV genotyping in cervical cancer screening that includes data from a complete cycle of the screening program. Our findings suggest a high prevalence of HPV-9valent genotypes and a significant association with an increased risk of developing > HSIL. This constitutes important data for health authorities, which may help define the future of vaccination and cervical cancer screening strategies.

Cytohistological findings in HPV‐negative cases from HPV primary screening programme: quality assurance study

To evaluate the risk of false HPV-negative results and possible related morphological abnormalities in HPV primary cervical cancer screening. Out of 53,661 HPV-negative cases, 5469 (10.2%) randomly selected cytology slides were evaluated as a part of the quality assurance protocol. The Bethesda category negative for intraepithelial lesion or malignancy (NILM) in the HPV-negative cases given was present in 95.4%. Due to cytology other than NILM, 0.4% of cases were referred to colposcopy and 4.2% to the follow-up in one year. In the follow-up HPV negativity and NILM cytology was present in 88.3% of attended women. Cases other than HPV negative and NILM were referred to colposcopy. One biopsy-proven histological HSIL was found in the first round and one in follow-up screening. More comprehensive genotyping of HSIL cases revealed genotypes 69 and 11. Only two HPV test negative cases with histological HSIL were revealed forming 0.04% of quality control group. In both cases, HPV genotype not included in screening tests was found. According to the results, the primary HPV test with cytology triage is an efficient and specific method for cervical cancer screening despite of the fact that some non-high-risk genotypes are missed.