Peripheral blood immune cell parameters in patients with high-grade squamous intraepithelial lesion (HSIL) and cervical cancer and their clinical value: a retrospective study.

Objective: The objective of this study was to delineate the profile of peripheral blood lymphocytic indices in patients afflicted with high-grade squamous intraepithelial lesions (HSIL) and cervical neoplasms, and to elucidate the correlation of these hematologic markers with the clinicopathological spectra in individuals diagnosed with cervical carcinoma. Methods: We adopted a retrospective case-control modality for this investigation. An aggregate of 39 HSIL patients and 42 cervical carcinoma patients, who were treated in our facility from July 2020 to September 2023, were meticulously selected. Each case of cervical malignancy was confirmed through rigorous histopathological scrutiny. Concomitantly, 31 healthy female individuals, who underwent prophylactic health evaluations during the corresponding timeframe, were enlisted as the baseline control group. We systematically gathered and analyzed clinical demographics, as well as the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), from peripheral blood samples. Pearson's correlation coefficient was deployed to dissect the interrelation between peripheral NLR and PLR concentrations and the clinicopathological features in the cervical cancer group. Results: Inter-group comparative analysis unveiled statistically substantial variances in the PLR and NLR values among the tripartite clusters (F = 36.941, 14.998, P < 0.001, respectively). Although discrepancy in NLR (P = 0.061) and PLR (P = 0.759) measures between the groups of cervical carcinoma and HSIL was not statistically appreciable, these indices were markedly elevated in the cervical carcinoma faction as juxtaposed with the normative control group (t = 5.094, 5.927; P < 0.001 for both parameters). A discernible gradation in peripheral blood PLR and NLR concentrations was noted when stratified by clinical stage and the profundity of myometrial invasion in cervical cancer subjects (P < 0.001). The correlation matrix demonstrated a positive liaison between peripheral blood PLR and the clinical gradation, as well as the invasiveness of the neoplastic cells into the muscularis propria (P < 0.05); a similar trend was observed with the NLR values (P < 0.05). Conclusion: Augmented NLR and PLR levels in peripheral blood specimens are indicative of HSIL and cervical malignancy. These hematological parameters exhibit a pronounced interconnection with clinical staging and muscular wall penetration depth, serving as potential discriminative biomarkers for the diagnosis and prognosis of cervical cancer.

Analysis of the clinical characteristics and surgical methods of high-grade squamous intraepithelial lesions of the cervix in postmenopausal women: A retrospective case study.

The purpose of this study was to thoroughly evaluate the clinical features and surgical options for high-grade squamous intraepithelial lesions (HSIL) in postmenopausal women. A total of 308 patients diagnosed with HSIL through colposcopic cervical biopsy and endocervical curettage were included. Their clinical characteristics, surgical treatments, and postoperative pathology were analyzed. Key findings include: 1. Patients with positive preoperative thinprep cytologic test (TCT) results and postoperative pathology indicating HSIL or squamous cell carcinoma (≥HSIL) were significantly more frequent than those with negative preoperative TCT results (P < .05). 2. Univariate analysis indicated significant impacts of TCT, human papillomavirus (HPV) type, transformation zone (TZ) location, and surgical technique on postoperative pathology (P < .05). 3. Logistic regression analysis confirmed significant influences of TCT, HPV type, TZ location, and surgical method on postoperative pathology outcomes (P < .05), showing that each unit increase in TZ raised the probability of ≥HSIL in postoperative pathology by 49.7%. In surgical comparisons, cold knife conization (CKC) and extrafascial hysterectomy resulted in 8.379 and 4.427 times higher probabilities of ≥HSIL in postoperative pathology, respectively, compared to loop electrosurgical excision procedure (LEEP). 4. Surgical methods significantly influenced margin results (P < .05). After LEEP, 17.5% of cases had positive margins, compared to 9.4% after CKC, and 3.7% after extrafascial hysterectomy, indicating the highest rate of positive surgical margins occurred with LEEP. 1. Combined TCT and HPV screening is crucial for cervical cancer prevention, early detection, and management in postmenopausal women. Women with positive results for both TCT and HPV should undergo colposcopic cervical biopsy and endocervical curettage. 2. For patients with TZ3, CKC is the recommended surgical option. 3. CKC is the preferred treatment for postmenopausal women with HSIL, as it effectively diagnoses and treats the lesion, showing superior outcomes in managing postmenopausal HSIL.

Cervical precancerous and cancerous lesions screening using Pap smear test at Provincial Referral Hospital of Bukavu, Eastern DR Congo: profile and recommendations to stakeholders.

Introduction: cervical cancer is a health concern worldwide. The South Kivu Province in the Eastern DR Congo is facing many cases of this disease but poorly screened and reported. The objective of this was to determine the prevalence of cell abnormalities at cervical cytology in a tertiary teaching hospital in Bukavu and their association with common risk factors of cervical cancer. Methods: a cross-sectional study was conducted on 142 women attending the Provincial Referral Hospital of Bukavu (HPGRB) from February to December 2021. Quantitative variables were described by their median following their asymmetric distributions and the qualitative variables in absolute and relative frequencies. Then the Chi-square test was used for the comparison of proportion. Results: forty-five percent of the participants had between three and five children. Twenty-two (15.5%) of the 142 patients reported to have two or more sexual partners and 17.5% reported the use of hormonal contraception. The prevalence of cell abnormalities at cervical cytology was 17% of which Low- Grade Squamous Intraepithelial Lesion (LSIL) was the most representative (12.9%). There was no statistically significant association between the common cervical risk factors and the occurrence of cell abnormalities. Conclusion: cervical pre-cancerous lesions are frequent in South Kivu province. The Pap smear test remains an early and affordable screening method and constitutes a secondary prevention strategy in women of 18 years and older in a low-income country such as DR Congo where vaccination against HPV is still hypothetic.

Análisis de la inmunidad de las mujeres infectadas por el virus del papiloma humano y su relación con la lesión intraepitelial cervical / Immunity analysis in women infected with human papillomavirus and its link with cervical intraepithelial lesion (IMVIR study)

Introducción: El objetivo principal es estudiar los marcadores de NK memoria presentes en sangre periférica en pacientes con lesiones cervicales intraepiteliales de alto grado CIN2/3 frente a mujeres sin lesiones o con lesiones de bajo grado. Los objetivos secundarios son estudiar la relación entre el perfil de las células NK memoria y la infección o no por VPH, así como la persistencia viral en las mujeres infectadas por VPH. Material y métodos: Se trata de un estudio observacional prospectivo de una cohorte de mujeres reclutadas desde el año 2019, durante un periodo de 2años, en la unidad del tracto genital inferior en las consultas de ginecología general del Instituto de Salud de la Mujer del Hospital Clínico San Carlos. Los grupos de pacientes incluidos en el estudio son el grupo de estudio: mujeres con infección por VPH y con lesión cervical de alto grado (CIN2+); el grupo control1: mujeres con infección por el VPH sin lesión cervical de alto grado, y el grupo control2: mujeres sin infección por el VPH y sin lesión. Resultados: Durante el estudio se han reclutado 115 pacientes. Nos encontramos con un mayor número de NK «memoria» en pacientes infectadas, tanto en el grupo control1 como en el grupo de estudio, en comparación con el grupo control2. Además, cuando se analizan las pacientes no fumadoras, la expresión de NKp30 es significativamente menor en el grupo control1. Conclusiones: Los resultados ponen de manifiesto una probable menor capacidad para desarrollar funciones adaptativas por parte de las células NK en estas pacientes fumadoras frente a las no fumadoras. Un mejor conocimiento de la biología de las células NK y su papel en la infección por el VPH podría permitir el desarrollo de estrategias para manipular su funcionamiento (inmunoterapias) con un propósito pronóstico y terapéutico.(AU)

Introduction: The main objective is to study the NK markers present in circulating blood in patients with high grade intraepithelial cervical lesions compared with women without lesions or low grade lesions. The secondary objectives of the study are to understand the relationship between the NK memory like cells and the infection with HPV, as well as the persistence of the infection. Methods and materials: It is an observational prospective study that studies women from 2019 for 2years seen in ginecology rooms in Hospital Clínico San Carlos. The group of patients studied are: women with infection by HPV and high grade lesions, women with infection by HPV but no lesion or low grade lesion and women without lesion or infection. Results: We have recruited 115 patients. We have found more memory like NK cells in patients infected by HPV. And when we analyze the non-smoking patients, the expression of NKp30 is lower in patients infected without lesion. Conclusions: The results show that there could be less capacity to generate an adaptative function by NK in smoking patients than in non-smoking. A better knowledge of the NK cells biology and its role in the infection by HPV could allow us to manipulate with a therapeutic and prognostic end.(AU)

The role of cervical elastography in the differential diagnosis of preinvasive and invasive lesions of the cervix.

STUDY OBJECTIVE: This study aims to evaluate the role of cervical elastography in the differential diagnosis of preinvasive and invasive lesions of the cervix. MATERIALS AND METHODS: A total of 95 women participated in this prospective study and were divided into the following groups: 19 healthy subjects (group 1) with normal cervicovaginal smear (CVS) and negative human papillomavirus test (HPV DNA), 19 women with normal cervical biopsy and normal final pathological result of cervical biopsy (group 2), 19 women with low-grade squamous intraepithelial lesion (LSIL) (group 3), 19 women with high-grade squamous intraepithelial lesion (HSIL) (group 4), and 19 women with cervical cancer (group 5). Clinical, demographic, histopathological, and elastographic results were compared between these groups. RESULTS: Comparing groups, age (40.42 ± 8.31 vs. 39.53 ± 8.96 vs. 38.79 ± 9.53 vs. 40.74 ± 7.42 vs. 54.63 ± 12.93, p < 0.001 respectively), gravida (1.74 ± 1.33 vs. 2.16 ± 1.68 vs. 2.21 ± 1.96 vs. 2.53 ± 1.93 vs. 4.63 ± 2.17 p < 0.001 respectively), parity (1.37 ± 0.68 vs. 1.68 ± 1.20 vs. 1.58 ± 1.30 vs. 2.00 ± 1.67 vs. 3.37 ± 1.61, p < 0.001 respectively), and the proportion of patients at menopause (10.5% vs., 15.8% vs. 10.5% vs. 5.3% vs. 57.9%, p < 0.01 respectively), a statistically significant difference was found (Table 1). However, no statistically significant difference was found in the number of abortions, BMI, mode of delivery, smoking, additional disease status, history of surgery, and family history (p > 0.05) (Table  2. As a result of the applied roc analysis, mean cervical elastographic stiffness degree (ESD) was found to be an influential factor in predicting cervical cancer (p < 0.05). The mean cut-off value was 44.65%, with a sensitivity of 94.7% and a specificity of 96.1% (Table 7). CONCLUSION: Measurement of ESD by elastography is a low-cost, easily applicable, and non-invasive indicator that can distinguish cervical cancer from normal cervical and preinvasive lesions. However, it is unsuitable for determining preinvasive cervical lesions from normal cervix.

Challenging lesions in cervical cytology: The elusive HSIL.

Cervical cytology has been an integral part of cervical cancer screening since the mid-20th century with the implementation of screening protocols utilising Pap testing. During that time, cervical cancer has gone from the leading cause of cancer deaths in women to not even appearing in the top 10 causes of US cancer deaths. However, despite its long and widespread use, cervical cytology remains a diagnostically challenging area in the practice of cytopathology. Of particular importance for diagnosticians is the accurate diagnosis of high-grade squamous intraepithelial lesions (HSILs), given the significant risk of progression to invasive cervical cancer and the importance to patient management. Therefore, this review is presented in order to highlight the diagnostic features of HSIL, its various appearances, and important benign and neoplastic differential considerations with an emphasis on morphological clues that can aid in distinguishing between these different processes.

Development of an Algorithm for Cervical High-Grade Squamous Intraepithelial Lesion Based on Breath Print Analysis.

OBJECTIVES: This study was designed to develop an algorithm for the diagnosis of cervical high-grade squamous intraepithelial lesions (HSIL), based on patterns of volatile organic compounds, evaluated using an e-nose. METHODS: For this pilot study, the study population consisted of a group of 25 patients with histologically confirmed HSIL and a group of 26 controls. Controls consisted of women visiting the outpatient department for gynecological complaints unrelated to cancer. Women had a negative high-risk human papillomavirus and/or normal cytology (negative for intraepithelial lesions of malignancy) of their most recent test performed in the context of participation in routine cervical cancer screening. Breath tests were performed and labeled with the correct diagnosis. Machine-learning techniques were used to develop a model for predicting HSIL. Based on the receiver operating characteristics curve, both sensitivity and specificity were calculated. RESULTS: Individual classifications of all patients with HSIL and controls, as calculated by the model, showed a sensitivity of 0.88 (95% CI = 0.68-0.97) and specificity of 0.92 (95% CI = 0.73-0.99). The positive predictive value and the negative predictive value were 0.92 (95% CI = 0.72-0.99) and 0.89 (95% CI = 0.70-0.97), respectively. The Cohen κ coefficient was 0.80. CONCLUSIONS: E-nose can detect distinctive patterns of volatile organic compounds between cervical HSIL patients and controls. Validation of the algorithm in further studies is necessary before possible implementation into daily practice.

Comparative measurement of D- and L-lactic acid isomers in vaginal secretions: association with high-grade cervical squamous intraepithelial lesions.

PURPOSE: Identification of low-cost protocols to identify women at elevated susceptibility to develop cervical intra-epithelial abnormalities would aid in more individualized monitoring. We evaluated whether quantitation of the D- and L-lactic acid isomers in vaginal secretions could differentiate women with normal cervical epithelia from those with a low (LSIL) or high (HSIL) grade squamous intraepithelial lesion or with cervical cancer. METHODS: Vaginal samples, collected from 78 women undetgoing cervical colposcopy and biopsy, were tested for pH, bacterial composition by Gram stain (Nugent score) and concentrations of D- and L-lactic acid by a colorimetric assay. RESULTS: Subsequent diagnosis was 23 women with normal cervical epithelium, 10 with LSIL, 43 with HSIL and 2 with cervical cancer. Vaginal pH and Nugent score were comparable in all subject groups. The concentration of L-lactic acid, but not D-lactic acid, as well as the L/D-lactic acid ratio, were significantly elevated (p < 0.01) in women with HSIL and cervical cancer. CONCLUSION: Comparative measurement of vaginal D- and L-lactic acid isomers may provide a low-cost alternative to identification of women with an elevated susceptibility to cervical abnormalities.

Squamous cell carcinoma antigen combined with HPV-16 infection in predicting high-grade squamous intraepithelial lesions of the cervix.

An early screening of HPV and the Thinprep Cytology Test (TCT) can effectively prevent cervical cancer. However, patients with high-grade cervical intraepithelial neoplasia usually escape current screening methods and commonly develop cervical cancer. Hence, to identify effective and specific screening methods for high-grade cervical intraepithelial neoplasia is of vital necessity. In this study, 541 patients collected in Sun Yat-Sen hospital from January 2007 to December 2016 were selected. HPV genotype detection and SCC-ag detection were done in these patients. It was found that when serum SCC-ag level exceeded over 0.39 ng/ml in HPV-16 positive patients, the sensitivity and specificity of this novel approach to predict high-grade cervical intraepithelial neoplasia could reach to 83.1% and 62.1%, respectively. The result suggested that the combination of serum SCC-ag level and HPV-16 infection could be used as a novel approach for high-grade cervical intraepithelial neoplasia screening.Impact statementWhat is already known on this subject? Patients with a high-grade cervical intraepithelial neoplasia usually escape current screening methods.What do the results of this study add? When serum SCC-ag level exceeded over 0.39 ng/ml in HPV-16 positive patients, the sensitivity and specificity to predict high-grade cervical intraepithelial neoplasia could reach to 83.1 and 62.1%, respectively.What are the implications of these findings for clinical practice and/or further research? Combination of serum SCC-ag level and HPV-16 infection could be used to screen high-grade cervical intraepithelial neoplasia.

Value of additional sections: Tissue handling of small biopsies in detecting squamous dysplasia of the uterine cervix.

Cervical cancer screening is currently based on high-risk human papillomavirus (HR-HPV) molecular testing, Pap cytology testing, and histologic evaluation of cervical biopsies. As primary HPV screening for cervical cancer becomes widely used, some of the recommended screening guidelines propose colposcopy and biopsies following positivity for HPV16/18 without cytologic triage. In such instances, a biopsy would be the only tissue sample available for informing further management. The use of additional histologic levels on cervical biopsies is commonly employed to achieve a diagnosis, although no set criteria for when to obtain additional levels exist. In this study, we evaluated the value of additional sections in cervical biopsy and endocervical curetting, as well as clinical and histologic features that should be considered when ordering additional levels. Additional levels were obtained for the following scenarios: benign mucosa with Pap discrepancy (HSIL or ASC-H interpretation), size discrepancy with the gross description, suspicious atypia for a high-grade lesion, and long-standing high-risk HPV infection. A change in diagnosis was observed in 21.4% of the cases, with an upgrade to a high-grade squamous intraepithelial lesion (CIN2-3) in 12.1% of cases. An initial impression of atypia significantly correlated with both a change in diagnosis and an upgrade to CIN2-3. In the era of primary HPV screening, when evaluating tissue samples following positive HPV test, small, atypical foci should be followed by additional levels. We recommend six (6) initial levels on all cervical biopsies, particularly if there is no loss of tissue between the levels, to ensure an accurate interpretation. This will be crucial in the timely and accurate identification of HPV-related intraepithelial lesions and proper subsequent management.

Alterações em exames citopatológicos realizados em Unidade Básica de Saúde: um estudo analítico transversal / Alterations in cytopathological tests performed in a Basic Health Unit: a cross-cutting analytical study

Objetivo: Com o presente estudo, buscou-se verificar a quantidade de exames de colpocitologia oncótica coletados em Unidade Básica de Saúde (UBS) escolhida, determinar quantas e quais são as alterações encontradas nesses exames e quais foram as condutas e acompanhamentos realizados em pacientes com exames alterados. Métodos: Foram analisados 446 exames de colpocitologia oncótica realizados em uma UBS do centro-oeste do Paraná. As pacientes com exame alterado foram selecionadas e foi feita uma análise desses prontuários a fim de verificar a conduta e o acompanhamento dessas pacientes. Resultados: Foram encontrados 32 exames com alterações, sendo três de uma mesma paciente. Dessas 30 pacientes, a grande maioria correspondia a células escamosas atípicas de significado indeterminado (ASC-US), possivelmente não neoplásicas, e 28 pacientes retornaram para receber uma conduta inicial, sendo principalmente o encaminhamento para a coleta de novo preventivo em seis meses ao serviço de oncologia clínica. Conclusão: O presente estudo concluiu que a hipótese principal foi verdadeira, a qual foi descrita como prevalência significativa de lesões intraepiteliais de alto grau, embora não seja a mais frequente, e descontinuidade por parte das pacientes que obtiveram esse resultado. Além disso, notou-se grande encaminhamento à atenção terciária, o que não é indicado pelo Ministério da Saúde.(AU)

Objective: With the present study, we sought to verify the amount of cytopathological tests collected in the chosen basic health unit, to determine how many and what are the alterations found in these tests and what were the conducts and follow-ups performed in patients with altered exams. Methods: We analyzed 446 preventive tests performed in a basic health unit in the Midwest of Paraná, and patients with altered examination were selected and an analysis of these medical records was made in order to verify the conduct and follow-up of the patients. Results: Thirty-two tests with alterations were performed, 3 of which were the same patient. Of these 30 patients, the vast majority corresponded to atypical cells of squamous meaning ­ possibly non-neoplastic (ASC-US), and 28 patients returned to receive an initial approach, mainly being referred to the collection of preventive new in 6 months and to the clinical oncology service. Conclusion: The present study concluded that the main hypothesis was true, which was described as a significant prevalence of high-grade intraepithelial lesions (HSIL), although not the most frequent, and discontinuity on the part of the patients who obtained this result. In addition, there was a large referral to tertiary care, which is not indicated by the Ministry of Health.(AU)

Riesgo de desarrollar LIE-AG en pacientes con tamizaje inicial positivo para VPH y citología cervicovaginal negativa en seguimiento hasta 10 años: revisión sistemática y metaanálisis / Risk of developing H-SIL in patients with initial positive screening for HPV and negative cervicovaginal cytology in follow-up up to 10 years: systematic review and meta-analysis

Resumen Introducción: El cáncer de cérvix es el segundo en frecuencia y el tercero en mortalidad; la infección por el virus del papiloma humano (VPH) está asociada al riesgo de cáncer; sin embargo, no se conoce el riesgo acumulado a 1, 2, 3, 5 y 10 años. Objetivo: Determinar el riesgo de las pacientes VPH positivo con evaluación inicial citológica negativa para desarrollar lesión intraepitelial de alto grado a lo largo del tiempo. Método: Se realizó una revisión sistemática de artículos en inglés y español de los últimos 20 años, usando las bases de datos PubMed, Cochrane, LILACS, ProQuest y Embase. Se incluyeron ensayos clínicos aleatorizados en los que se determinaba el estado VPH y se realizaba seguimiento con citología cervicovaginal a 1, 2, 3, 5 y 10 años en mujeres de 20-64 años. Resultados: Se incluyeron siete ensayos clínicos aleatorizados, con un total de 98.521 mujeres, de ellas 8820 VPH positivo y 89.701 VPH negativo al ingreso, seguidas hasta por 10 años con citología cervicovaginal, encontrando que la infección por VPH es un factor de riesgo para desarrollar lesiones intraepiteliales de alto grado a 2, 5 y 10 años, con un riesgo relativo de 110.94 (79.41-154.97), 83.65 (55.22-126.73) y 29.71 (5.72-154.33), respectivamente. Conclusiones: La infección por VPH es un factor de riesgo importante para el desarrollo de lesiones intraepiteliales de alto grado a 2, 5 y 10 años.

Abstract Introduction: Cervical cancer is the second in frequency and the third in mortality, infection by the human papillomavirus (HPV) is associated with the risk of increased cancer; however, the cumulative risk of 1, 2, 3, 5 and 10 years is not known. Objective: To determine the risk of HPV-positive patients with negative initial cytological evaluation for developing high-grade intraepithelial lesion over time. Method: A systematic review of articles in English and Spanish in the last 20 years was carried out, using the PubMed, Cochrane, LILACS, ProQuest and Embase databases. Randomized clinical trials were included in which HPV was performed and subsequent follow-up with cervicovaginal cytology at 1, 2, 3, 5 and 10 years in women aged 20-64 years. Results: Seven randomized clinical trials were included, a total of 98,521 women, 8820 with positive HPV and 89701 negative on admission and followed up for up to 10 years with cervicovaginal cytology. Finding that HPV infection is a risk factor for developing high-grade intraepithelial lesion at 2, 5 and 10 years with a relative risk of 110.94 (79.41-154.97), 83.65 (55.22- 126.73) and 29.71 (5.72-154.33), respectively. Conclusions: HPV infection is an important risk factor for the development of high-grade intraepithelial lesion at 2, 5 and 10 years.

The feature of cervical microbiota associated with the progression of cervical cancer among reproductive females.

OBJECTIVES: The aim of this study was to characterize cervical microbiome feature of reproductive-age women in the progression of squamous intraepithelial lesions (SIL) to cervical cancer. METHODS: We characterized the 16S rDNA cervical mucus microbiome in 94 participants (age from 18 to 52), including 13 cervical cancer (CA), 31 high-grade SIL (HSIL), 10 low-grade SIL (LSIL), 12 HPV-infected (NH) patients and 28 healthy controls (NN). Alpha (within sample) diversity was examined by Shannon and Simpson index, while Beta (between sample) diversity by principle coordinate analysis (PCoA) of weighted Unifrac distances. Relative abundance of microbial taxa was compared using Linear Discriminant Analysis Effect Size (LEfSe). Co-occurrence analysis was performed to identify correlation among marker genera, and Phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt) to explore functional features and pathways of cervical microbiota. RESULTS: Alpha diversity(p < 0.05) was higher in severer cervical pathology with lower relative abundance of Lactobacillus as well as higher of anaerobes. Beta diversity (p < 0.01) was significantly different. Marker genera were identified including Porphyromonas, Prevotella and Campylobacter of CA and Sneathia of HSIL. The correlation of differential functional pathways with Prevotella was opposite to that with Lactobacillus. CONCLUSION: Our study suggests differences in cervical microbiota diversity and relative abundance of reproductive-age females in different stages of cervical carcinogenesis. Marker genera might participate in the lesion progression and will be helpful for diagnosis, prevention and treatment. These findings may lead the way to further study of the cervical microbiome in development of cervical cancer.

Rescreening of high-risk HPV positive Papanicolaou tests initially screened as negative is a low yield procedure in the era of HPV genotyping.

INTRODUCTION: Many laboratories rescreen Papanicolaou test slides initially interpreted as negative, but positive for human papillomavirus (HPV) high-risk types, as a quality control measure. We have evaluated the utility of this practice in the era of HPV genotyping as a laboratory improvement project. MATERIAL AND METHODS: Between August 2016 and October 2019, we identified 3618 rescreened Papanicolaou tests with follow-up biopsies. The biopsy results were put into 3 groups: 1) Negative; 2) LSIL: HPV changes or low-grade squamous intraepithelial lesion; and 3) HSIL: high-grade squamous intraepithelial lesion or carcinoma. HPV molecular testing results with subtyping for types 16 and 18 were available for 3117 of these cases. RESULTS: A total of 530 of 2812 Papanicolaou tests (18.8%) with positive HPV results were reinterpreted as cytologically abnormal after rescreening; 75 (14.2%) had a biopsy result of HSIL. The subset positive for HPV types 16/18 had 38 of 133 cytology positive cases diagnosed as HSIL on biopsy vs. 107 of 935 cytology negative cases diagnosed as HSIL on biopsy (28.6% vs. 11.4%, P < 0.0001). The subset positive for "other" (non-16/18) high-risk HPV types had 37 of 397 cytology positive follow-up HSIL vs. 84 of 1288 cytology negative follow-up HSIL (9.3% vs. 6.5%, P = 0.075). CONCLUSIONS: Rescreening has the highest yield in specimens positive for types 16/18. However, for this group colposcopy is recommended regardless of cytology findings, reducing the patient benefit. Routine rescreening of cytology negative/HPV positive Papanicolaou tests has reduced utility when HPV subtyping is performed and should be reconsidered.

Possible high-grade squamous intraepithelial lesion (pHSIL) in the new cervical screening paradigm: The outcomes and the role of clinicopathological review.

BACKGROUND: A renewed National Cervical Screening Program (NCSP) was introduced in Australia in December 2017. Under the renewed NCSP, there are limited data to guide the management of discordant colposcopy and biopsy results after a liquid-based cytology (LBC) finding of 'possible high-grade squamous intraepithelial lesion' (pHSIL). AIMS: This study aims to determine the proportion of women referred with pHSIL who are found to have HSIL, identify influencing factors of women most at risk, and examine the role that cytopathology review plays in management decisions. MATERIALS AND METHODS: Two-hundred and thirty-two women presenting to a tertiary women's hospital in Australia with pHSIL since December 2017 were identified. Women with HSIL following colposcopy directed biopsy were referred for treatment. When HSIL was not identified, these patients were referred for multidisciplinary clinicopathological review. Pathological outcomes and treatment recommendations are included. MAIN OUTCOME MEASURES: The primary outcome of the study was histological confirmation of HSIL. RESULTS: Primary outcome data were available for 182 women (78.5%); 62 (34.1%) had HSIL on histology, three (1.7%) had adenocarcinoma in situ (AIS) and one (1%) had cervical squamous cell carcinoma (SCC). There was no association between age and the presence of HSIL. The presence of human papillomavirus 16 and/or 18 increased the likelihood of HSIL on histology (relative risk 1.9; 95% CI 1.27-2.80, P = 0.002). Fifty-nine (25.4%) women were referred for observation who had low-grade squamous intraepithelial lesion/no dysplasia. CONCLUSIONS: Clinicopathological review optimises management and triage of patients with pHSIL on referral cytology. Understanding outcomes in these patients informs counselling and management.

Multi-center clinical study using optical coherence tomography for evaluation of cervical lesions in-vivo.

In this prospective study of an in-vivo cervical examination using optical coherence tomography (OCT), we evaluated the diagnostic value of non-invasive and real-time OCT in cervical precancerous lesions and cancer diagnosis, and determined the characteristics of OCT images. 733 patients from 5 Chinese hospitals were inspected with OCT and colposcopy-directed biopsy. The OCT images were compared with the histological sections to find out the characteristics of various categories of lesions. The OCT images were also interpreted by 3 investigators to make a 2-class classification, and the results were compared against the pathological results. Various structures of the cervical tissue were clearly observed in OCT images, which matched well with the corresponding histological sections. The OCT diagnosis results delivered a sensitivity of 87.0% (95% confidence interval, CI 82.2-90.7%), a specificity of 84.1% (95% CI 80.3-87.2%), and an overall accuracy of 85.1%. Both good consistency of OCT images and histological images and satisfactory diagnosis results were provided by OCT. Due to its features of non-invasion, real-time, and accuracy, OCT is valuable for the in-vivo evaluation of cervical lesions and has the potential to be one of the routine cervical diagnosis methods.

Detection of HIV mRNA in routine liquid-based cytology specimens of HIV-infected women.

OBJECTIVE: Human immunodeficiency virus-infected women have a high incidence of HPV infection, and HIV and HPV coinfection is associated with high incidence of cervical intraepithelial lesions and cervical cancer. This study investigated the ability to detect HIV mRNA in routine screening cervical liquid-based cytology (LBC) samples and its correlation with HPV coinfection and cervical intraepithelial lesions. METHODS: Liquid-based cytology samples from 80 HIV-infected women under combined antiretroviral therapy (cART) were studied for detection of HIV and HPV mRNA using Aptima® tests and for cytology diagnosis according to the 2014 Bethesda System for Reporting Cervical Cytology. Peripheral blood (PB) HIV mRNAs were assessed by real-time polymerase chain reaction (RT-PCR). Statistical analysis used Fisher's exact or Chi-square test to compare frequencies among groups and the Mann-Whitney U test to compare continuous variables. RESULTS: Human immunodeficiency virus mRNA was present in 21.3% of routine LBC samples in HIV-infected women, 12.5% of which had no detectable PB viral load. Among 10 patients diagnosed with high-grade squamous intraepithelial lesion (HSIL), 50% had detectable HIV viral load. The occurrence of HSIL vs low-grade intraepithelial lesion/negative intraepithelial lesion or malignancy in LBC samples was significantly higher in women with detectable HIV viral load (P = .029). CONCLUSIONS: Human immunodeficiency virus mRNA was present in routine LBC samples in HIV-positive women under cART. Detection of HIV viral load in LBC is significantly associated with cervical HSIL. This suggests the relevance of HIV mRNA viral load assessment in routine LBC, to evaluate patients' infectious potential and monitor efficacy of the cART scheme.

Pap Smear miR-92a-5p and miR-155-5p as potential diagnostic biomarkers of squamous intraepithelial cervical cancer.

BACKGROUND: one of the female-specific diseases with a high incidence and mortality is cervical cancer. The main cause of cervical cancer is infection with Human papilloma virus (HPV). Low-grade squamous intraepithelial lesions (LSIL) and High-grade squamous intraepithelial lesions (HSIL) usually is caused by an HPV infection. Considering the role of microRNAs (miRNAs) as diagnostic biomarkers for a variety of cancers, the aim of this study was to determine miR-92a-5p and miR-155-5p expression levels in LSIL and HSIL Pap Smear samples. METHODS: After initial bioinformatic studies, A total of 75 samples (25 samples of patients with LSIL, 25 patients with HSIL and 25 healthy individuals) were subjected to RNA extraction and cDNA synthesis. The expressions levels of confirmed miRNAs in samples of patients with LSIL, HSIL and healthy individuals were evaluated by Real time PCR analysis. To demonstration the role of predicted miRNAs as novel biomarkers in diagnosis of LSIL and HSIL, ROC curve analysis was done. RESULTS: Bioinformatics results showed that miR-92a-5p and miR-155-5p target the HPV E6 and E7 genes. The expression levels of these miRNAs were strikingly higher in Pap smear of patients with LSIL than in the healthy individuals (35.36, P = 0.001) (62.23, P = 0.001). Similarity, expression levels of miR-92a-5p and miR-155-5p were amazingly higher in patients with HSIL than in the healthy individuals (33.62, P= 0.001) (69.07, P= 0.001). Although, the levels of miR-92a-5p (0.95, P = 0. 85) and miR-155-5p (1.11, P = 0.84) exhibited no statistical differences between patients with LSIL and HSIL. Also, ROC curve analyses verified that miR-92a-5p and miR-155-5p are specific and sensitive and may serve as new biomarkers for the early detection of cervical cancer. CONCLUSION: These data suggest miR-92a-5p and miR-155-5p, which are upregulated in LSIL and HSIL, can be consider as predictive biomarkers for the prognosis of cervical cancer patients.
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Evaluation of a real-time optoelectronic method in the diagnostics of CIN over four years of observations.

Cervical cancer is considered to be particularly amenable to prevention and highly treatable in its early stages. The real-time optoelectronic method of cervix examination seemed to be very promising in the detection of cervical squamous intraepithelial lesions and demonstrated relatively good efficacy. Although this method was introduced into clinics almost 10 years ago, it has not found its place in diagnostic schemes. At the moment, cytological smears and HPV detection with genotyping are still essential. TruScreen seems to be a slightly forgotten test. The aim of the study was to evaluate the efficacy and accuracy of TruScreen in detecting cervical pathology: CIN and cervical cancer confirmed with a histopathological diagnosis in comparison with other methods-cytology and colposcopy over four years of observations. The study was conducted on 130 women with abnormal Pap smear results. We can conclude that a real-time optoelectronic method like TruScreen can be useful as an effective initial cervical cancer screening in developing countries, possibly in combination with other methods. The combination of cytology and TruScreen examination may help clinicians to take decision about the next diagnostics steps (e.g. colposcopy) and contribute to better primary screening for cervical cancer.