Negative For Intraepithelial Lesion Or Malignancy Research Articles

TLR4 Downregulation Identifies High-Risk HPV Infection and Integration in H-SIL and Squamous Cell Carcinomas of the Uterine Cervix.

Growing scientific evidence suggests a link between the expression of toll-like receptor 4 (TLR4) and cervical cancer carcinogenesis. Specifically, a close relation between TLR4 expression and FIGO stage, lymph node metastases, and tumor size has been reported in cervical cancer. In the present study, we aimed to evaluate the relationship between TLR4 expression levels and human papillomavirus (HPV) infection and/or high-risk (hr) HPV integration status in patients with a histological diagnosis of high-grade squamous intraepithelial lesion (H-SIL), and squamous cell carcinoma (SCC) of the uterine cervix. Sixty biopsies of cervical neoplasia, comprising H-SIL (n = 20) and SCC (n = 40), were evaluated for TLR4 expression by immunohistochemistry. All samples were positive for high-risk HPV as confirmed by in situ hybridization (ISH) and broad-spectrum PCR followed by Sanger sequencing analysis. The intensity of TLR4 staining was higher in tissues negative for intraepithelial lesion or malignancy (NILM) than in H-SIL, and further reduced in SCC. Moreover, statistically significant differences have been observed in the percentage of TLR4 expression between NILM and H-SIL and between H-SIL and SCC, with higher percentages of expression in H-SIL than in SCC. Our results showed a significant downregulation of TLR4 in HPV-related H-SIL and SCC, compared to NILM. These data support the hypothesis that TLR4 expression is suppressed in HPV-driven oncogenesis.

Unsatisfactory Pap Test Results: A Critical Patient Management Problem Pre-Analytically Addressed by the Cytopathology Laboratory.

The unsatisfactory rate of Pap tests (PT) is an important quality assurance (QA) metric for a cytopathology laboratory. At our institution, an unsatisfactory PT slide is followed by a second ThinPrep (TP) slide. The aim of this study is to evaluate this QA practice. Our laboratory processes an unsatisfactory TP PT with a follow-up second TP slide with or without glacial acetic acid. The correlation between the unsatisfactory rate and the second slide rate test was examined. A total of 2739 cases with a second TP slide were prepared for an unsatisfactory initial TP PT. After second slide preparation, 780 cases (28%) remained unsatisfactory. Using Spearman's rank correlation test, there was a notable negative correlation between the unsatisfactory rate and the second slide rate (rho = -0.42). Of those PTs recategorized as satisfactory TP, 1742 were negative for intraepithelial lesion or malignancy (NILM) (89%), 135 as atypical squamous cells of undetermined significance (ASC-US) (7%), 37 as low-grade squamous intraepithelial lesion (LSIL) (1.9%), 11 as atypical squamous cells cannot exclude high-grade squamous intraepithelial lesion (ASC-H) (0.6%), 8 as high-grade squamous intraepithelial lesion (HSIL) (0.4%), and 20 as atypical glandular cells (AGC) (1%). The final Bethesda categorization for all cases and the human papilloma virus (HPV) data was tabulated. A second slide preparation significantly reduced the unsatisfactory rate of the PT. This also had a significant impact by detecting clinically significant lesions. HPV testing can also be performed on slides reclassified from unsatisfactory to ASC-US or higher.

The role of cervicovaginal microbiota in the occurrence of severe cervical intraepithelial dysplasia

BACKGROUND: Despite the availability of visual examination of the cervix, cervical screening in Russia has not been widespread enough, and therefore the incidence of cervical cancer remains consistently high. In recent years, the vaginal microbiota is given special attention as a risk factor for the development of precancerous diseases of the cervix. AIM: The aim of this study was to compare the cervicovaginal microbiota in patients with high-grade squamous intraepithelial lesions (HSIL) or negative for intraepithelial lesions or malignancy (NILM). MATERIALS AND METHODS: Microorganisms isolated from the cervicovaginal microbiota were identified in 40 patients using the mass spectrometry method. 20 women had severe cervical dysplasia, and the other 20 were healthy women without precancerous cervical lesions. RESULTS: Corynebacterium spp. and Streptococcus spp. were found more often in the cervicovaginal microbiome in patients with high-grade squamous intraepithelial lesions than in women negative for intraepithelial lesions or malignancy. CONCLUSIONS: The data obtained suggest that the presence of Corynebacterium spp. and Streptococcus spp. in the cervicovaginal microbiota is associated with the presence of severe cervical intraepithelial changes.

Pap Smears Cytology of Cervical Abnormalities in Derna, Libya

The study aimed to provide information about the prevalence of various cervical lesions diagnosed by Papanicolaou smear tests among women in the city of Derna, in eastern Libya. The reporting of the Pap smears is based on the 2014 Bethesda system. The study included seventy-two cervical Pap smears cytology received at the Noor-AL-Huda Medical Center Pathology Laboratory in Derna City, east of Libya, and processed using conventional smear techniques. The data was gathered retrospectively from March 2022 to August 2023. A total of 72 cervical Pap smears were included in the study. The majority of the cases reported were Negative for Intraepithelial Lesions or Malignancy (NILM) 54 (75%). Out of the 72 reports, 2 (2.7%) were unsatisfactory. Low-grade Squamous Intraepithelial Lesions (LSIL) were found in 8 cases (11.11%), and 4 (5.5%) were High-grade Intraepithelial Lesions (HSIL). Atypical Squamous Cells cannot exclude HSIL (ASC-H) were found in 4 cases (5.5%). LSIL and HSIL were more common among women aged 30-40 years. The age of the patients included in this study ranged from 30 to 56, with a mean age of 40 years. These findings emphasize the importance of a well-organized cervical screening program. In particular, women over 30 years should be educated about the importance of Pap smears and encouraged to undergo regular screening.

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.

Prevalence, risk factors and genotype distribution of human papillomavirus infection among women with and without invasive cervical cancer: Findings from a hospital-based study in Bihar, India.

Background Human papillomavirus (HPV) infection is largely responsible for the development of invasive cervical cancer (ICC). Its prevalence, risk factors and genotype distribution among women residing in Bihar (third most populous Indian state) with and without ICC are not well known. Methods In this hospital-based study, we followed up 1439 participants with cytology and HPV report. HPV detection and genotyping were performed using the TaqMan-based real-time PCR method. Clinical and sociodemographic data were collected and analysed using statistical methods. Results The overall prevalence of HPV infection was 37.3% (537/1439) and 11 different types of HPV genotypes were observed. Higher HPV positivity was found in premalignant, intraepithelial and invasive malignant lesions of the cervix; 73.8% (93/126) of atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (ASC-H) and high-grade squamous intraepithelial lesions (HSIL) and 93.4% (114/122) of invasive malignancies were infected with HPV in comparison to only 26.1% (245/938) of negative for intraepithelial lesion or malignancy (NILM) cytology. Moreover, HPV was found in 95.2% (236/248) of histologically confirmed cases of carcinoma cervix. HPV16 and HPV18 infections were reported in 78.2% (194/248) and 8.9% (22/248), respectively. The remaining patients had infection with other high-risk strains/co-infection with multiple strains or were HPV-negative. Various socio-demographic factors including women >50 years of age, >10 years of marriage and high parity were significantly associated with HPV infection. Conclusion Our data suggest that HPV16 infection may be the major cause for ICC among women residing in Bihar. Our findings may serve as a baseline for developing an appropriate screening and vaccination strategy for Bihar.

The role of endocervical curettage in the diagnosis of cervical intraepithelial neoplasia in human papillomavirus positive patients.

The role of endocervical curettage (ECC) in the diagnosis of cervical intraepithelial neoplasia (CIN) is a controversial topic. Investigate the role of ECC in the diagnosis of CIN in human papillomavirus (HPV) positive patients. Retrospective. A tertiary training and research hospital. This study included patients who were referred for colposcopy between 2018-2022 because of abnormal screening results. ECC results, age, cytology, HPV status, and colposcopic impression of the patients were extracted from the medical records. Multinomial logistic regression analyses were performed to identify factors that could predict CIN on ECC. The likelihood of high-grade squamous intraepithelial lesions (HSIL) in ECC in patients with cervical biopsy results of normal and low-grade squamous intraepithelial lesion (LSIL). 2895 women. In patients with normal and LSIL cervical biopsy results, HSILs were detected in 6.7% of ECC results. There was no difference in the detection rates of CIN in ECC among groups with smear results negative for intraepithelial lesions or malignancy (NILM), atypical squamous cells of undetermined significance (ASC-US), and LSIL. The likelihood of HSIL being observed in ECC was 2.2 times higher in patients with HPV16. The probability of LSIL disanois was 2.3 times higher in women aged 50-59 years and 2.8 times higher in women ≥ 60 years compared to the reference group of <30 years. The probability of LSIL was 2.3 and HSIL by ECC was 2.2 times higher in both age categories (P<.012 and P=.032, respectively) than the reference group of <30 years. Regardless of colposcopic findings, ECC should be performed in patients with smear results of NILM who are positive for HPV16, in patients with smear results of ASC-US and LSIL who are positive for any oncogenic type of HPV and in patients 50 and above with any result of smear or any oncogenic HPV type. We did not have the components of the HPV types in mixed groups.

Cervical Cytology-Histopathology Concordance and Role of Dual Immunomarkers in Biopsy Samples of Uterine Cervix: A Cross-sectional Study from a Tertiary Care Hospital of West Bengal, India

Introduction: Cervical cancer is one of the leading causes of cancer deaths. Liquid-based cervical cytology enables the detection and diagnosis of the disease at an early stage. p40 is a specific immunomarker that distinguishes squamous cell carcinomas from other cervical carcinomas with glandular and neuroendocrine differentiation. Aim: To determine the role of Liquid-based Cytology (LBC) in the early detection of premalignant and malignant lesions of the uterine cervix and its concordance with histopathological findings. Materials and Methods: This cross-sectional study was conducted at the Institute of Post Graduate Medical Education and Research (IPGME&amp;R), Kolkata, West Bengal, India, over a period of one year and six months (from October 2020 to March 2022). Cervical samples were collected from a total of 200 females, and the materials were processed using the BD SurePath™ LBC method. The cytologically confirmed cases were biopsied, and histopathological concordance was established. Immunohistochemical (IHC) staining for p40 and p63 was performed using the peroxidase-antiperoxidase method to differentiate between premalignant, malignant squamous, and glandular lesions of the uterine cervix. For quantitative analysis, all cells were counted in 10 random fields at 400x magnification, and p63 and p40 were expressed as a percentage of positive cells per the total number of counted cells. Cases were considered positive if 5% or more of the tumour cell nuclei showed brown nuclear staining. The mean percentage positivity of p63 and p40 nuclear staining of all the cases in each category was calculated for non neoplastic and precursor/neoplastic lesions of the cervix. Results: Among the 200 cases evaluated by LBC, 169 (84.5%) were non neoplastic, and the remaining 31 (15.5%) were precursor/neoplastic lesions. The vast majority (126 cases, 63%) were inflammatory smears, followed by 20 cases (10%) that were Negative for Intraepithelial Lesion or Malignancy (NILM). Total of 40 cases were followed-up with biopsy and histopathology, and concordance with the cytological diagnosis was evaluated. Among 40 cases, 23 were precursor/ neoplastic on histopathology, and seven cases that were non neoplastic on Histopathological Examination (HPE) had been correctly diagnosed on LBC, giving a concordance rate of 75%. The overall sensitivity, specificity, Positive Predictive Value (PPV), and Negative Predictive Value (NPV) of LBC were 92%, 46.6%, 74.1%, and 77.7%, respectively, considering histological diagnosis as the gold standard. Regarding IHC expression on histopathology, the mean positivity of p40 and p63 for non neoplastic lesions was 9.40% and 10.06%, and for precursor/neoplastic lesions, 47.44% and 46.4%, respectively. Adenocarcinoma-in-situ and adenocarcinoma were negative for both p40 and p63. Conclusion: Cervical cytology is a less invasive, cost-effective, and simple procedure to diagnose cervical epithelial cell abnormalities. Cytological-histopathological concordance revealed that LBC is a sensitive diagnostic method. The comparison between non neoplastic and neoplastic lesions of the cervix revealed a statistically significant difference with respect to the mean percent positivity of p40 and p63 IHC staining. Both of these markers can be used to differentiate squamous cell carcinoma from adenocarcinoma of the cervix.

Cervical Cytology-Histopathology Concordance and Role of Dual Immunomarkers in Biopsy Samples of Uterine Cervix: A Cross-sectional Study from a Tertiary Care Hospital of West Bengal, India

Introduction: Cervical cancer is one of the leading causes of cancer deaths. Liquid-based cervical cytology enables the detection and diagnosis of the disease at an early stage. p40 is a specific immunomarker that distinguishes squamous cell carcinomas from other cervical carcinomas with glandular and neuroendocrine differentiation. Aim: To determine the role of Liquid-based Cytology (LBC) in the early detection of premalignant and malignant lesions of the uterine cervix and its concordance with histopathological findings. Materials and Methods: This cross-sectional study was conducted at the Institute of Post Graduate Medical Education and Research (IPGME&amp;R), Kolkata, West Bengal, India, over a period of one year and six months (from October 2020 to March 2022). Cervical samples were collected from a total of 200 females, and the materials were processed using the BD SurePath™ LBC method. The cytologically confirmed cases were biopsied, and histopathological concordance was established. Immunohistochemical (IHC) staining for p40 and p63 was performed using the peroxidase-antiperoxidase method to differentiate between premalignant, malignant squamous, and glandular lesions of the uterine cervix. For quantitative analysis, all cells were counted in 10 random fields at 400x magnification, and p63 and p40 were expressed as a percentage of positive cells per the total number of counted cells. Cases were considered positive if 5% or more of the tumour cell nuclei showed brown nuclear staining. The mean percentage positivity of p63 and p40 nuclear staining of all the cases in each category was calculated for non neoplastic and precursor/neoplastic lesions of the cervix. Results: Among the 200 cases evaluated by LBC, 169 (84.5%) were non neoplastic, and the remaining 31 (15.5%) were precursor/neoplastic lesions. The vast majority (126 cases, 63%) were inflammatory smears, followed by 20 cases (10%) that were Negative for Intraepithelial Lesion or Malignancy (NILM). Total of 40 cases were followed-up with biopsy and histopathology, and concordance with the cytological diagnosis was evaluated. Among 40 cases, 23 were precursor/ neoplastic on histopathology, and seven cases that were non neoplastic on Histopathological Examination (HPE) had been correctly diagnosed on LBC, giving a concordance rate of 75%. The overall sensitivity, specificity, Positive Predictive Value (PPV), and Negative Predictive Value (NPV) of LBC were 92%, 46.6%, 74.1%, and 77.7%, respectively, considering histological diagnosis as the gold standard. Regarding IHC expression on histopathology, the mean positivity of p40 and p63 for non neoplastic lesions was 9.40% and 10.06%, and for precursor/neoplastic lesions, 47.44% and 46.4%, respectively. Adenocarcinoma-in-situ and adenocarcinoma were negative for both p40 and p63. Conclusion: Cervical cytology is a less invasive, cost-effective, and simple procedure to diagnose cervical epithelial cell abnormalities. Cytological-histopathological concordance revealed that LBC is a sensitive diagnostic method. The comparison between non neoplastic and neoplastic lesions of the cervix revealed a statistically significant difference with respect to the mean percent positivity of p40 and p63 IHC staining. Both of these markers can be used to differentiate squamous cell carcinoma from adenocarcinoma of the cervix.

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.

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.

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.