Cervical Squamous Intraepithelial Lesions Research Articles

The value of Ki67 for the diagnosis of LSIL and the problems of p16 in the diagnosis of HSIL

p16 and Ki67 are immunohistochemical markers related to cervical squamous intraepithelial lesions. p16 has been widely used to assist in the diagnosis of high-grade squamous intraepithelial lesions. However, a conclusion about the role of Ki67 in the diagnosis of squamous intraepithelial lesions has not been established. The aim of this study was to analyze the role of p16 and Ki67 immunohistochemical staining in assisting cervical squamous intraepithelial lesions. This study performed immunohistochemical staining for p16 and Ki67 on 1024 cervical biopsy specimens at our hospital to compare the differences between p16 and Ki67 in different cervical lesions using the chi-squared test and Fisher’s exact test. This study also evaluated the value of Ki67 for the diagnosis of low-grade squamous intraepithelial lesions (LSILs) using the receiver operating characteristic curve. The results indicated that Ki67 had high specificity and sensitivity in distinguishing LSIL from normal cervix. p16 was diffusely and strongly positive in some LSILs, and some problems were encountered in the interpretation of p16 staining. Therefore, we believe that Ki67 can be used as an immunohistochemical marker to help in the diagnosis of LSIL, to distinguish lesions that are difficult to morphologically determine and to avoid misdiagnosis. The practical application of p16 staining is still problematic. It may be necessary to find other auxiliary means to distinguish this small proportion of cervical lesions.

Therapeutic effects of topical photodynamic therapy with 5-aminolevulinic acid on cervical high-grade squamous intraepithelial lesions

BackgroundTopical photodynamic therapy with 5-aminolevulinic acid (ALA-PDT) is a non-invasive option for treatment of Cervical Intraepithelial Neoplasia (CIN). We investigated the clinical efficacy and safety of ALA-PDT in treatment of patients with cervical high-grade squamous intraepithelial lesion (HSIL) and evaluated the factors that effect the efficacy of PDT. MethodsA total of 99 patients (average age: 30 years (18–45 years old)) with cervical HSIL and high-risk Human Papilloma Virus (hr-HPV) infections and who had received ALA-PDT were enrolled in this retrospective study. Before ALA-PDT, cervical exfoliated cells from all patients were obtained for HPV genotyping, liquid-based cytology test (LBC) and PAX1 methylation (PAX1m) test. Then, 6 months after ALA-PDT, HPV genotyping, LBC and colposcopy-directed biopsy were conducted. During subsequent follow-up, HPV genotyping and LBC were performed, and colposcopy-directed biopsy was conducted if hr-HPV was positive and/or LBC result was abnormal. ResultsAt 6 months after treatment, total HPV clearance and lesions complete remission (CR) rates were 64.6% (64/99) and 88.9% (88/99), while at 1-year of follow-up, they were 81.3% (65/80) and 92.5% (74/80), respectively. At 1-year follow-up, HPV clearance rate was higher, relative to 6 months after ALA-PDT (p <0.05). At 6 months after treatment, HPV clearance and CR rates in the PAX1 hypermethylation (PAX1hm) group were 36.8% and 73.7%, which were lower compared to the rates for PAX1 hypomethylation (PAX1lm) group (71.3%, 92.5%) (p <0.05). Moreover, of the 11 patients with cervical canal lesions, 3 (3/7, 42.9%) patients had cervical canal HSIL persistence and the other 4 cervical canal HSIL and all of the 4 cervical canal LSIL had complete remission. ConclusionsALA-PDT is an effective, safe treatment approach for patients with cervical HSIL and hr-HPV infections. Patients with PAX1lm showed better therapeutic outcomes than patients with PAX1hm or cervical canal HSIL.

Persistent ferroptosis promotes cervical squamous intraepithelial lesion development and oncogenesis by regulating KRAS expression in patients with high risk-HPV infection

Cervical squamous cell carcinoma (CSCC) is a type of female cancer that affects millions of families worldwide. Human papillomavirus (HPV) infection is the main reason for CSCC formation, and squamous intraepithelial lesions (SILs) induced by high-risk HPV (HR-HPV) infection are considered precancerous lesions. A previous study reported that HPV-infected cancer cells were able to counteract lipid peroxidation for survival. Recent research has reported that ferroptosis acts in an iron-dependent lipid peroxidation manner to kill cancer cells, and it is proposed as a new approach for female cancer therapy. Here, we investigated the role of ferroptosis throughout SIL development into CSCC. We found that ferroptosis occurred in SIL, but anti-ferroptosis emerged in CSCC. Our data further indicated that an antiferroptotic effect was formed in response to persistent ferroptosis and then promoted oncogenesis. Altogether, we provide novel insight into ferroptosis in cervical SIL development and suggest a potential therapeutic target for the treatment of CSCC.

Diagnostic Management of Oncogenic HPV Cervical Infections: The Field Experience in Wuxi, China.

IntroductionA liquid-based cytology test was introduced for cervical cancer screening in the 2000s worldwide. However, the concordance of diagnostic findings between the liquid-based cytology test and cervical biopsy has not been fully investigated, especially the overall failure rate on the diagnosis of cervical cancer and high-grade squamous intraepithelial lesion (HSIL) by cytology testing. The aim of this retrospective study was to investigate the concordance between ThinPrep cytology and histology test in the diagnosis of cervical cancer and HSIL in HPV-positive women.MethodsThinPrep cytology test was performed in 2,472 HPV-positive women. Out of 2,472 HPV-positive women, the cervical biopsy was concurrently performed in 1,533 women. Data on the HPV type and the diagnostic findings of the ThinPrep cytology test and cervical biopsy were collected from our hospital electronic database. The concordance of diagnostic findings between cytology and histology was compared.ResultsThe rate of agreement in the diagnosis of the low-grade squamous intraepithelial lesion (LSIL) or HSIL between cervical biopsy and ThinPrep cytology test was 58 or 49%. The overall false negative rate in the diagnosis of cervical cancer and HSIL by ThinPrep cytology test was 6%. However, when considering the total number of HPV-positive women diagnosed with cervical cancer (n = 36) and HSIL (n = 117) by cervical biopsy, we found that a significant number of HPV-positive women with cervical cancer (n = 12, 33%), or women with HSIL (n = 77, 66%) were failed to be diagnosed by the ThinPrep cytology test. These HPV-positive women were either diagnosed with cervical infection or ASCUS, or LSIL.DiscussionOur data demonstrated that in order to ensure an accurate diagnosis, an immediate cervical biopsy in women with cervical infection or ASCUS or LSIL should be strongly recommended in clinical practice.

Dual-attention EfficientNet based on multi-view feature fusion for cervical squamous intraepithelial lesions diagnosis

Cervicograms are widely used in cervical cancer screening but exhibit a high misdiagnosis rate. Even senior experts show only 48% specificity on clinical examinations. Most existing methods only use single-view images applied with acetic acid or Lugol’s iodine solution as their input data, ignoring the fact that non-pathological tissues may show false-positive reactions in these single-view images. This can lead to misdiagnosis in clinical diagnosis. Therefore, it is essential to extract features from multi-view colposcopy images (including the original images) as inputs, because three-view cervicograms provide complementary information. In this work, we propose an improved EfficientNet based on multi-view feature fusion for the automatic diagnosis of cervical squamous intraepithelial lesions. Specifically, EfficientNet-B0 is employed as the backbone network, and three-view images are taken as inputs by channel cascading to reduce misclassification. Additionally, we propose a dual-attention mechanism that implements the feature selection function based on Convolution Block Attention Module (CBAM) and Coordinate Attention (CA). These two attention mechanisms assist each other to enhance the feature representation of HSIL. We leverage a dataset of 3294 clinical cervigrams and obtain 90.0% accuracy with recall, specificity, and F1-Score of 87.1%, 93.0%, and 89.7%, respectively. Experimental results prove that this method can help clinicians with precise disease classification and diagnosis, and outperforms known related works.

Evaluation of 5-aminolevulinic acid-mediated photodynamic therapy on cervical low-grade squamous intraepithelial lesions with high-risk HPV infection

BackgroundThe treatment options for low‐grade squamous intraepithelial neoplasia (LSIL) of the cervix with high-risk HPV infection have not been standardized. Studies show that photodynamic therapy (PDT) mediated by 5-aminolevulinic acid (ALA-PDT) might be effective. In this retrospective study, the clinical efficacy and safety of ALA-PDT in the treatment of LSIL were evaluated. MethodsALA-PDT was performed in 55 LSIL patients aged 21–45 years who also showed high-risk HPV infection and cervical ectropion. HPV test, cytology, colposcopy and pathology were examined before and after treatment. Meanwhile, PDT-related symptoms and adverse reactions were also reviewed. ResultsAt 6-month follow-up after PDT, except for 5 patients who showed the persistence of LSIL lesions, the pathological regression ratio of 90.1% (50/55) was achieved. No HPV-DNA was detected in exfoliated cervical cells in 81.8% (45/55) patients. Among them, the HPV clearance ratio of I Degree cervical ectropion was 96.2%, significantly higher than that of II Degree (70.8%) and III Degree (60%). Significant shrunk of cervical ectropion and reduction of vaginal secretions after PDT were seen in 78.0% patients. ConclusionALA-PDT is a safe and effective therapeutic option for patients of reproductive age who suffer from LSIL with high-risk HPV infection and cervical ectropion.

Importance of the Immune Microenvironment in the Spontaneous Regression of Cervical Squamous Intraepithelial Lesions (cSIL) and Implications for Immunotherapy.

Cervical high-grade squamous intraepithelial lesions (cHSILs) develop as a result of a persistent high-risk human papilloma virus (hrHPV) infection. The natural course of cHSIL is hard to predict, depending on a multitude of viral, clinical, and immunological factors. Local immunity is pivotal in the pathogenesis, spontaneous regression, and progression of cervical dysplasia; however, the underlying mechanisms are unknown. The aim of this review is to outline the changes in the immune microenvironment in spontaneous regression, persistence, and responses to (immuno)therapy. In lesion persistence and progression, the immune microenvironment of cHSIL is characterized by a lack of intraepithelial CD3+, CD4+, and CD8+ T cell infiltrates and Langerhans cells compared to the normal epithelium and by an increased number of CD25+FoxP3+ regulatory T cells (Tregs) and CD163+ M2 macrophages. Spontaneous regression is characterized by low numbers of Tregs, more intraepithelial CD8+ T cells, and a high CD4+/CD25+ T cell ratio. A ‘hot’ immune microenvironment appears to be essential for spontaneous regression of cHSIL. Moreover, immunotherapy, such as imiquimod and therapeutic HPV vaccination, may enhance a preexisting pro-inflammatory immune environment contributing to lesion regression. The preexisting immune composition may reflect the potential for lesion regression, leading to a possible immune biomarker for immunotherapy in cHSILs.

Topical imiquimod compared with conization to treat cervical high-grade squamous intraepithelial lesions: Multicenter, randomized controlled trial

ObjectiveIn a previous phase II trial, we showed that topical imiquimod (IMQ) therapy is an efficacious treatment for high-grade squamous intraepithelial lesion (HSIL). Aim of the present study was to investigate the non-inferiority of a 16-week topical, self-applied IMQ therapy compared to large loop excision of the transformation zone (LLETZ) in patients diagnosed with HSIL. MethodsPhase III randomized, controlled, multicenter, open trial performed by Austrian Gynecologic Oncology group. Patients with histologically proven cervical intraepithelial neoplasia (CIN)2 (30 years and older) or CIN3 (18 years and older) and satisfactory colposcopy were randomized to topical IMQ treatment or LLETZ. Successful treatment was defined as negative HPV high-risk test result 6 months after start of the treatment. Secondary endpoints were histological outcome and HPV clearance rates. ResultsWithin 3 years 93 patients were randomized, received the allocated treatment and were available for ITT analysis. In the IMQ group negative HPV test at 6 months after treatment start was observed in 22/51 (43.1%) of patients compared to 27/42 (64.3%) in the LLETZ group on ITT analysis (rate difference 21.2%-points, 95% two-sided CI: 0.8 to 39.1). In the IMQ group histologic regression 6 months after treatment was observed in 32/51 (63%) of patients and complete histologic remission was observed in 19/51 (37%) of patients. Complete surgical resection was observed in 84% after LLETZ. ConclusionIn women with HSIL, IMQ treatment results in lower HPV clearance rates when compared to LLETZ. LLETZ remains the standard for women with HSIL when treatment is required.Clinical Trial Registration: ClinicalTrials.gov Identifier: NCT01283763, EudraCT number: 2012-004518-32.

Features of HPV infection and screening characteristics of high-risk HPV negative in patients with cervical high-grade squamous intraepithelial lesion: a retrospective analysis of 459 cases

Features of HPV infection and screening characteristics of high-risk HPV negative in patients with cervical high-grade squamous intraepithelial lesion: a retrospective analysis of 459 cases

Classification of Cervical Precursor Lesions via Local Histogram and Cell Morphometric Features.

Cervical squamous intra-epithelial lesions (SIL) are precursor cancer lesions and their diagnosis is important because patients have a chance to be cured before cancer develops. In the diagnosis of the disease, pathologists decide by considering the cell distribution from the basal to the upper membrane. The idea, inspired by the pathologists' point of view, is based on the fact that cell amounts differ in the basal, central, and upper regions of tissue according to the level of Cervical Intraepithelial Neoplasia (CIN). Therefore, histogram information can be used for tissue classification so that the model can be explainable. In this study, two different classification schemes are proposed to show that the local histogram is a useful feature for the classification of cervical tissues. The first classifier is Kullback Leibler divergence-based, and the second one is the classification of the histogram by combining the embedding feature vector from morphometric features. These algorithms have been tested on a public dataset.The method we propose in the study achieved an accuracy performance of 78.69% in a data set where morphology-based methods were 69.07% and Convolutional Neural Network (CNN) patch-based algorithms were 75.77%. The proposed statistical features are robust for tackling real-life problems as they operate independently of the lesions manifold.

Risk factors and prevalence of cervical squamous intraepithelial lesions among women in south India: A community-based cross-sectional study.

">Cervical cancer in India accounts for one-fifth of the global burden. Well-defined precancerous stages help early detection of the disease. Apart from human papillomavirus, the risk factors include age, education, occupation, early age at marriage and first delivery, abortions, and multiple sexual partners. Prevalence and risk factors for cervical squamous intraepithelial lesions (SIL) among women by Pap smear screening in south India were analyzed through a cross-sectional study. ">Women from rural and urban area were motivated by local accredited social health activists to attend pre-fixed Pap smear clinics in government hospitals. Pap smears collected in these clinics were taken to the Regional Cancer Centre, Thiruvananthapuram, processed, and cytology reports were prepared. Multiple logistic regression analysis was used to identify risk factors for SIL and high-grade SIL (HSIL). ">The number of SIL was 67 out of 10,580 and HSIL was 39. Having higher education (Odds Ratio, OR:0.05(95% Confidence Interval, CI: 0.01-0.2), being married but living single (OR : 5.3, 95%CI:2.4-11.5), Having >2 abortions (OR:21, 95% CI:4.5-24), having younger age at delivery (OR : 0.1, 95% CI:0.01-0.3) and having unhealthy cervix (OR: 16.4, 95% CI:6.2-42.7) were the factors found to be the associated risk factors in multiple regression analysis. ">Pap smear screening can be focused on women with risk factors such as low education, married but living single, having >2 abortions, younger age at delivery, and unhealthy cervix on per speculum examination.

Can We Reduce Overtreatment of Cervical High-Grade Squamous Intraepithelial Lesions?

The aim was to evaluate the cytology, colposcopic, and pathological factors associated with the absence of high-grade squamous intraepithelial lesion (HSIL)/cervical intraepithelial neoplasia (CIN) 2-3 lesion on loop electrosurgical excision procedure (LEEP) specimens in women with high-grade cytology and/or HSIL/CIN 2-3 biopsy and the risk of disease persistence/recurrence. Two-center retrospective study of women undergoing LEEP for high-grade cervical disease between January 2014 and December 2019. Clinical, cytology, colposcopy, and pathology results were evaluated to identify independent predictive factors associated with CIN 1/negative LEEP results. Univariate and multivariate logistic regression models were performed. Follow-up data was evaluated to assess the risk of HSIL/CIN 2-3 persistence/recurrence. Six hundred thirty-nine of 801 women (79.8%) had high-grade cytology and 631 (78.8%) HSIL/CIN 2-3 biopsy. High-risk human papillomavirus test was positive in 98% of women. Loop electrosurgical excision procedure specimen showing CIN 1 or less was found in 27%-31%. Normal/low-grade colposcopy (odds ratio [OR] = 2.17, CI = 1.39-3.39, p = .001) and CIN 1/negative biopsy (OR = 3.25, CI = 2.12-4.99, p < .001) were predictors of negative/CIN 1 LEEP result in women with high-grade cytology. Normal/low-grade cytology (OR = 1.77, CI = 1.19-2.64, p = .005), normal/low-grade colposcopy (OR = 1.66, CI = 1.11-2.49, p = .013), and CIN 2 biopsy (OR = 2.75, CI = 1.73-4.39, p < .001) were predictors in women with HSIL/CIN 2-3 biopsy. Women with a negative/CIN 1 LEEP had lower recurrence/persistence than those with confirmed HSIL/CIN 2-3(1 vs 31, p = .002). Positive endocervical margin (OR = 2.85, CI = 1.10-7.36, p = .03) and high-risk human papillomavirus persistence (OR = 41.3, CI = 16-106.7, p < .01) were predictors of HSIL/CIN 2-3 persistence/recurrence. A CIN 1/negative LEEP specimen in women with high-grade cytology and/or HSIL/CIN 2-3 biopsy is associated with negative/low-grade cytology, normal/low-grade colposcopic findings and CIN 2 biopsy result before treatment. The HSIL/CIN 2-3 disease persistence/recurrence is low when LEEP specimen does not confirm HSIL/CIN 2-3.

A case report and literature review of delayed telogen effluvium after topical imiquimod use in treating a cervical high-grade squamous intraepithelial lesion

The use of imiquimod in cervical intraepithelial lesions has been evaluated in different trials and was found associated with various and numerous adverse events. Telogen effluvium is an infrequent systemic adverse event observed mainly in patients experiencing severe systemic adverse reactions. This paper presents the case of a young woman who developed telogen effluvium after intravaginal imiquimod use that was not preceded by other systemic adverse events and resolved gradually after nine months. Telogen effluvium after intravaginal imiquimod use is rare, may appear without any preceding severe adverse event, and may persist for an extended period.

Topical 5-Aminolevulinic Acid Photodynamic Therapy for Cervical High-Grade Squamous Intraepithelial Lesions

Topical 5-Aminolevulinic Acid Photodynamic Therapy for Cervical High-Grade Squamous Intraepithelial Lesions

The magnitude and predictors of cervical squamous intraepithelial lesions among women in Enugu, Nigeria: a cross-sectional study of women in a low-resource setting.

Introductionthe prevalence of cervical squamous intraepithelial lesion is not well appreciated in most low-income countries. The study aimed to determine the level of awareness, prevalence and the pattern of squamous intraepithelial lesions and predictors for abnormal Pap smear reports (development of pre-malignant lesions of the cervix) among women attending various clinics in a tertiary health facility in Enugu, Nigeria.Methodsa cross-sectional study of 207 female patients attending various clinics of Enugu State University Teaching Hospital, Parklane, Enugu between June and August 2017 was undertaken. Structured interviewer-administered questionnaires were used for data collection while cervical smears were collected from the patients and sent for cytology. Data analysis was done using the Statistical Package for the Social Sciences (SPSS) version 22.0. The results were presented as means, standard deviations, frequencies and proportions. Pearson´s Chi-square test was used to test for associations between categorical variables and statistical significance was set at a p-value of < 0.05.Resultsthe levels of awareness of cervical cancer and the screening methods among the respondents were 76.8% and 36.7% respectively. The overall knowledge of cervical cancer and its screening was poor (6.8% and 29.0% respectively). The prevalence of pre-malignant lesions of the cervix among the respondents was 15.0% with low grade squamous intraepithelial lesion (LGSIL) having the highest frequency (38.7%). Among all the other risk factors for the development of premalignant lesions of the cervix among the respondents, a report of abnormal pap (positive) smear report was significantly associated with only age ≥35 years (χ2=5.723; p=0.017). The same age of 35 years and above also correctly predicted abnormal Pap smear reports among other factors (AOR = 3.02, 95% CI = 1.16 - 7.89, p = 0.024).Conclusionthe awareness of cervical cancer and cervical cancer screening was high but the overall knowledge on cervical cancer and its screening was very poor among the respondents. The prevalence of pre-malignant lesions of the cervix was high, and the commonest abnormal smear was LGSIL. Only age 35 years and above correctly predicted the occurrence of abnormal Pap smear reports among the respondents.

Correlation between Lactobacillus and expression of E-cadherin, β-catenin, N-cadherin, and Vimentin in postmenopausal cervical lesions.

To detect the correlation between Lactobacillus vaginalis and the expression of epithelial-mesenchymal transition (EMT)-related factors, E-cadherin, β-catenin, N-cadherin, and Vimentin, in postmenopausal cervical squamous intraepithelial lesions (SILs) and cervical squamous cell carcinoma (SCC), and to explore the possible mechanism. From January 2016 to January 2020, 30 postmenopausal patients with low-grade SIL (LSIL), 18 patients with high-grade SIL (HSIL), and 30 patients with SCC who underwent colposcopy biopsy in the Outpatient Department of the First Affiliated Hospital of Inner Mongolia Medical University were selected as the experimental group, and 30 postmenopausal normal women were selected as the control group. The expression of 16SrRNA of Lactobacillus vaginalis in each group was determined by the 16S third-generation full-length amplification sequencing technique. The mRNA expression levels of E-cadherin, β-catenin, N-cadherin, and Vimentin were detected by quantitative real-time polymerase chain reaction (qPCR). The correlation between the 16SrRNA expression level of Lactobacillus vaginalis and the mRNA expression level of the EMT-related proteins was compared among all groups. (I) The progression of postmenopausal cervical SILs to cervical SCC was significantly positively correlated with age, number of pregnancies, smoking, pH value, positive rate of HPV16, and negatively correlated with total Lactobacillus 16SrRNA expression (P<0.0001). (II) The level of vaginal microbiota in postmenopausal women showed that Lactobacillus iners was dominant. With the progression of the disease, the expression levels of 16SrRNA in Lactobacillus iners and Lactobacillus total vagina decreased gradually, and the differences were statistically significant (P<0.05). (III) With the disease progresses. The expression of total Lactobacillus 16SrRNA was positively correlated with the mRNA expression of β-catenin and E-cadherin (r>0; P<0.05), and negatively correlated with the mRNA expression of Vimentin and N-cadherin (r<0; P<0.05). In postmenopausal women, Lactobacillus vaginalis interacts with HPV and is associated with the occurrence of EMT, promoting the development of cervical lesions.

Cervical Pap smear is gold diagnostic tool for cervical cancer

One hundred (100) female patients referring to AL-Zahraa Teaching Hospital in ALNajaf Province who were suspected to harbor Cervical squamous intraepithelial lesions were included in this study. Cytological examination were performed for their Papsmeared and stained cervical cellular scrapes and according to their main cytological finding they were divided into three cytological groups: Cervicitis with Squamous intraepithelial lesions, Cervicitis without Squamous intraepithelial lesions and healthy group. A full history taking and clinical gynecological examination of all these (3) groups was performed. The following summarized results were found: 1-Cervicitis with SILs was 22% (HSILs 5%, LSILs 63% and Asc-us 32%),Cervicitis without SILs was 58% and 10% healthy patients. 2-The mean age of patients presented with cervical intraepithelial lesions was (44.23± 10.2)years. The highest percentage was diagnosed in the age stratum (36-50 ) years. 3- the clinical presentation of the patients with cervical neoplasia were indistinguishable from other cytological group, However, among many other finding related to the history and clinical examinations, early of marriage, multiparity, smoker behavior, abnormal vaginal bleeding were found significantly higher in cervical premalignant lesions than other cytological group.

Comparison of Conservative Treatment of Cervical Intraepithelial Lesions with Imiquimod with Standard Excisional Technique Using LLETZ: A Randomized Controlled Trial

(1) Background: There are limited data on the success of conservative treatment of high-grade cervical squamous intraepithelial lesions (HSIL) with imiquimod directly compared to standard of treatment with LLETZ. (2) Methods: Patients aged 18–40 with histological HSIL (with high-grade cervical intraepithelial neoplasia, CIN2p16+ and CIN3), were randomly assigned to treatment with imiquimod or LLETZ. The primary outcome was defined as the absence of HSIL after either treatment modality. The secondary outcomes were the occurrence of side effects. (3) Results: 52 patients were allocated in each group and were similar regarding baseline characteristics. In the imiquimod group, 82.7% of patients completed treatment, which was successful in 51.9%. All patients in the LLETZ group completed treatment, which was successful in 92.3% (p < 0.001). In the subgroup of CIN2p16+ patients, treatment with imiquimod was not inferior to LLETZ (73.9% vs. 84.2%, p = 0.477). During and after treatment, no cases of progression to cancer were observed. Side effects and severe side effects (local and systemic) were more prevalent in the imiquimod than in the LLETZ group (88.5% vs. 44.2% (p-value < 0.001) and 51.9% vs. 13.5% (p-value < 0.001), respectively). (4) Conclusion: Generally, in patients with HSIL, LLETZ remains the gold standard of treatment. However, in a subgroup analysis of patients with CIN2p16+, the success rate was comparable between the two treatment modalities. Due to the prevalence of side effects, the treatment compliance with imiquimod use may, however, present a clinically important issue.

Prognostic value of HPV 16/18 genotyping and geminin mRNA quantification in low-grade cervical squamous intraepithelial lesion

ABSTRACT Low-grade cervical squamous intraepithelial lesion is a precancerous neoplasia that has appreciable probability to evolve into malignancy. To explore the prognostic value of HPV 16/18 genotyping and geminin mRNA quantification in predicting the progressiveness of LSIL. We recruited 212 participants who were negative for intraepithelial lesion or malignancy (NILM 76), low-grade squamous intraepithelial lesion (LSIL 85), high-grade squamous intraepithelial lesion (HSIL 36) and cervical intraepithelial neoplasia grade cervical cancer grade 3, (CIN3 15) patients. Tissues were obtained during excisional treatment. HPV 16/18 genotyping and geminin mRNA qRT-PCR were performed. HPV 16/18 positivity rate and geminin mRNA level were integrated with the clinical parameters into a multivariate logistic model. Area under curve was yielded based on receiver operation curve derived from this multivariate logistic model. Follow-up visits were performed to LSIL patients with progression. HSIL patients have higher HPV 16/18 positivity rate and geminin mRNA levels than LSIL. Among HSIL, CIN3 have higher HPV 16/18 positivity rate and geminin mRNA levels. Multivariate logistic analysis showed that HPV 16/18 positivity and geminin mRNA expression status are independent factors for differentiating HSIL and LSIL. The baseline HPV 16/18 positivity rate and geminin mRNA levels of 18 LSIL patients who developed HSIL are significantly higher than non-progressive LSIL patients. The values examined at follow-up timepoints were also higher than baseline. These results suggest that geminin is implicated in the progression of LSIL and combining HPV 16/18 genotyping and geminin mRNA qRT-PCR could potentially differentiating the progressive LSIL and improve the efficacy of clinical intervention.

A comparison of high-risk human papillomavirus DNA detection between urine and cervical sample testing in women with abnormal Pap smears.

To compare the clinical performance of high-risk human papillomavirus (hrHPV) DNA detection between urine and cervical samples collected from the same patient for the detection of CIN2+ lesions (high-grade squamous intraepithelial lesions or cervical cancer lesions). The secondary objectives were to evaluate agreement among hrHPV genotypes and to compare patient satisfaction between urine and cervical sample collection. This prospective cross-sectional study enrolled 96 women with abnormal cervical cytology who attended the colposcopy clinic at Siriraj Hospital (Bangkok, Thailand) between July 2016 and January 2017. Self-collected random-voiding and first stream urine samples were collected into a universal sterile urine container and immediately mixing with preservative before the pelvic examination. Cervical tissue sampling was performed according to standard treatment guidelines. Both specimens were sent for extraction and detection of hrHPV by Anyplex II HPV high-risk testing. Study patients were surveyed to compare patient satisfaction between urine and cervical sample collection. Carcinogenic hrHPV positive rate was 73% in urine samples and 81% in cervical samples. The sensitivity for HPV in the detection CIN2+ was high in both the urine and cervical groups at 86.2% and 94.8%, respectively. Agreement between the urine and cervical groups for HPV 16 or 18 detection was high, with kappa values of 0.86 for subtypes 16/18. Urine specimen collection had significantly higher satisfaction and acceptability than cervical specimen collection. Urine hrHPV testing by real-time polymerase chain reaction demonstrated high sensitivity and accuracy for the detection of CIN2+ lesions, with very good agreement when compared with cervical sample testing.