scholarly journals The Expression of HPV E6/E7 mRNA in Situ Hybridization in HPV Typing-negative Cervical Cancer

2021 ◽  
Author(s):  
Yating Xu ◽  
Yonghong Sun ◽  
Hui Chang ◽  
Jingjing Cai ◽  
Chengcheng Cao ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
In Situ Hybridization ◽  
Hpv Infection ◽  
Detection Methods ◽  
Positive Group ◽  
Hpv E6 ◽  
Mrna In Situ Hybridization ◽  
Hpv Typing ◽  
Significant Difference

Abstract Background: High-risk human papilloma virus (HR-HPV) persistent infection is the major tumorigenesis factor for cervical cancer (CC) and cervical intraepithelial neoplasia (CIN). However, the incidence of HPV-negative CC is approximately 5%-30% with different HPV detection methods. HR-HPV E6/E7 mRNA in situ hybridization (RISH) can detect HPV-driven tumours. Our study aimed to explore whether HPV typing-negative CC was caused by HPV infection.Methods: The records of CC patients with HPV typing results who had undergone cervical biopsies, cervical conization or hysterectomies were collected from April 2018 to September 2021 at the Affiliated Hospital of Weifang Medical University. RISH was detected using RNAscope chromogenicin in the tissues of patients with CC. Immunohistochemistry (IHC) was performed to evaluate the expression of p16INK4a and Ki67. CC patients with positive HPV typing in the same period were collected as controls.Results: A total of 308 women with HPV typing results were enrolled, and 30 (9.74%) cases of HPV typing were negative, including 22/30 (73.3%) cases of squamous cell carcinoma (SCC) and 8/30 (26.7%) cases of adenocarcinoma. In the CC patients who were HPV typing-negative, 28/30 (93.3%) were positive for RISH and p16INK4a block+ staining, which contained 22/22 (100%) SCCs and 6/8 (75%) adenocarcinomas. RISH was positive in 278/278 (100%) HPV typing-positive CCs, which included 232/232 (100%) SCCs and 46/46 (100%) adenocarcinomas. While 273/278 (98.2%) showed p16INK4a block+ staining, the five negative cases were SCC. Positive RISH in HPV typing-negative CC was significantly lower than in the HPV typing-positive group (P=0.002, 95% CI: 0.848-1.027). However, this significant difference only existed in adenocarcinoma, and positive RISH in HPV typing-negative SCC was the same as in the HPV typing-positive group. No significant differences were seen in the expression of p16INK4a and Ki67 (P=0.291, 95% CI: 0.863-1.047 and P=0.174, 95% CI: 0.905-1.033).Conclusions: HPV typing may cause misdiagnosis in 9.74% of CC patients, and HPV E6/E7 mRNA can detect the majority of CC with HPV-related status even in HPV typing-negative patients. This approach could provide a novel option to accurately detect HR-HPVs in cervical tumours and help to eliminate the percentage of misdiagnosed HPV-related cases.

scholarly journals Prognostic nomogram for patients with invasive endocervical adenocarcinoma incorporating HPV E6/E7 mRNA in situ hybridization and clinical characteristics

2020 ◽  
Author(s):  
Li-Li Liu ◽  
Shu-Lin Chen ◽  
Shu-Mei Yan ◽  
Yue Li ◽  
Xia Yang ◽  
...  
Keyword(s):  
In Situ Hybridization ◽  
Multivariable Analysis ◽  
Figo Stage ◽  
Cancer Center ◽  
Specific Method ◽  
Endocervical Adenocarcinoma ◽  
Hpv E6 ◽  
Mrna In Situ Hybridization ◽  
Significant Difference

Abstract Background: Human papillomavirus (HPV) E6/E7 mRNA in situ hybridization (HPV E6/E7 RNAscope) appears to be a sensitive and specific method. We aimed to examine the diagnostic and prognostic utility of this technique in endocervical adenocarcinoma (ECA) and build a useful prognostic nomogram model using this approach. Methods: The model was constructed from a retrospective study of 200 patients with ECA who had undergone surgery at Sun Yat-sen University Cancer Center between 2010 and 2014. The model's predictive efficiency and discriminative capability were defined by a concordance index (C-index) and calibration curve. Results: The overall sensitivity and specificity of HPV E6/E7 RNAscope for distinguishing HPV-associated adenocarcinoma (HPVA) from non HPV-associated adenocarcinoma (NHPVA) in the whole cohort were 75.8% and 80%, respectively, compared to 60.2% and 90.0% for p16 immunohistochemistry, 80.5% and 80.0% for HPV DNA, and 63.3% and 50% for HPV genotype. The independent factors derived from multivariable analysis of the whole cohort to predict overall survival (OS) were age, lymphovascular invasion (LVI), lymph node involvement (LNI), and HPV E6/E7 RNAscope, which were all incorporated into the nomogram with (nomogram B) or without (nomogram A) FIGO stage and treatment. The C-index of nomogram A for predicting OS was 0.825 (p = 0.002 and p < 0.001), which was significantly higher than the C-index for FIGO stage (0.653) and treatment (0.578). No significant difference occurred between nomograms A (0.825) and B (0.836). Furthermore, a risk stratification system was established to accurately stratify patients with ECA into two subgroups with significantly different prognosis. Conclusions: HPV E6/E7 RNAscope is highly specific for ECA, and the proposed nomogram using HPV E6/E7 RNAscope showed more accurate outcome in terms of prognosis in patients with ECA.

HR-HPV E6/E7 mRNA In Situ Hybridization

2017 ◽  
Vol 41 (5) ◽  
pp. 607-615 ◽  
Author(s):  
Anne M. Mills ◽  
Dawn C. Dirks ◽  
Melinda D. Poulter ◽  
Stacey E. Mills ◽  
Mark H. Stoler
Keyword(s):  
In Situ Hybridization ◽  
Hpv E6 ◽  
Mrna In Situ Hybridization

Correlation of MCM2 Detection with Stage and Virology of Cervical Cancer

2014 ◽  
Vol 29 (4) ◽  
pp. 363-371 ◽  
Author(s):  
Sérgio Menezes Amaro Filho ◽  
Gerard Jerry Nuovo ◽  
Cynthia B Cunha ◽  
Luiza De Oliveira Ramos Pereira ◽  
Michelle Oliveira-Silva ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
In Situ Hybridization ◽  
Tumor Staging ◽  
Invasive Cervical Cancer ◽  
Figo Stage ◽  
Hpv Dna ◽  
Significant Difference ◽  
Infected Cells ◽  
Hpv Types

The highly conserved mini-chromosome maintenance proteins (MCM) are important in the initiation of DNA replication. Few studies have correlated MCM expression with the progression of cancer. Objectives (i) To analyze the expression of MCM2 in cervical cancer; (ii) to correlate MCM2 expression with the clinical tumor staging according to FIGO classification, and (iii) to relate HPV type to MCM2 expression. Methods Tissue micro-arrays (TMA) from patients with invasive cervical cancer and controls were analyzed. Human papillomavirus (HPV) DNA detection and HPV types were determined by in situ hybridization, PCR, and sequencing. MCM2 expression was analyzed by immunohistochemistry. Results The most prevalent HPV types found in invasive cancer were HPV 16 (66.6%), followed by HPV 33 (11.8%), and HPV 35 (3.6%). An increased (p<0.05) expression of MCM2 was found in invasive cervical cancers compared to controls. Moreover, a strong correlation was found between the MCM2-positive cells and the presence of HPV DNA detected by in situ hybridization. No statistically significant difference was observed between MCM2 expression and FIGO stage. Conclusions The present study shows that HPV-infected cells strongly express MCM2; nevertheless, our data suggests that MCM2 is not a good biomarker when comparing the different clinical stages of cervical cancer.

scholarly journals HPV E6/E7 mRNA In Situ Hybridization in Endocervical Adenocarcinoma: Implications for Prognosis and Diagnosis

2021 ◽  
Author(s):  
Rong-Zhen Luo ◽  
Shu-Lin Chen ◽  
Mei Li ◽  
Yue Li ◽  
Xia Yang ◽  
...  
Keyword(s):  
Regression Analysis ◽  
In Situ Hybridization ◽  
Univariate Analysis ◽  
Figo Stage ◽  
Clinicopathological Parameters ◽  
Cox Regression Analysis ◽  
Endocervical Adenocarcinoma ◽  
Hpv E6 ◽  
Mrna In Situ Hybridization

Abstract Background: Human papillomavirus (HPV) E6/E7 mRNA in situ hybridization (HPV E6/E7 RNAscope) appears to be a sensitive and specific technique in detecting transcriptionally active HPV. We aimed to examine the diagnostic utility of this technique in endocervical adenocarcinoma (ECA), to explore the prognostic factors for ECA patients and develop a clinically useful nomogram based on clinicopathological parameters to predict it.Methods: We retrospectively analyzed 200 patients with ECA who had undergone surgery at Sun Yat-sen University Cancer Center from 2010 and 2014. The diagnostic performance of HPV E6/E7 RNAscope were evaluated by receiver operating characteristic (ROC) curve. A prognostic nomogram model including HPV E6/E7 RNAscope was generated based on multivariate Cox regression analysis, then we compared the predictive accuracy of the prognostic model with FIGO staging and treatment using concordance index (C-index), time-dependent ROC (tdROC), and decision curve analysis (DCA).Results: The sensitivity and specificity of HPV E6/E7 RNAscope for distinguishing HPV-associated adenocarcinoma (HPVA) from non-HPV-associated adenocarcinoma (NHPVA) in the whole cohort were 75.8% and 80%, respectively. According the univariate analysis and multivariate logistic regression analysis, age, lymphovascular invasion (LVI), lymph node involvement (LNI), and HPV E6/E7 RNAscope were valuable predictive factors for OS. These parameters were incorporated into the nomogram model (nomogram A) compared with FIGO stage and treatment. The C-index of nomogram A for predicting OS was 0.825, which was significantly higher than FIGO stage (C-index = 0.653, p=0.002) and treatment (C-index = 0.578, p < 0.001).Conclusions: HPV E6/E7 RNAscope is highly specific for ECA, and the 4-variable nomogram showed more accurate prognostic outcomes in patients with ECA.

In situ hybridization detection methods for HPV16 E6/E7 mRNA in identifying transcriptionally active HPV infection of oropharyngeal carcinoma: an updating

2018 ◽  
Vol 74 ◽  
pp. 32-42 ◽  
Author(s):  
Chiara C. Volpi ◽  
Chiara M. Ciniselli ◽  
Ambra V. Gualeni ◽  
Maddalena Plebani ◽  
Salvatore Alfieri ◽  
...  
Keyword(s):  
In Situ Hybridization ◽  
Hpv Infection ◽  
Detection Methods ◽  
Oropharyngeal Carcinoma ◽  
Hpv16 E6 ◽  
Hybridization Detection

scholarly journals HPV E6/E7 mRNA in situ hybridization in endocervical adenocarcinoma: implications for prognosis and diagnosis

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Rong-Zhen Luo ◽  
Shu-Lin Chen ◽  
Mei Li ◽  
Yue Li ◽  
Xia Yang ◽  
...  
Keyword(s):  
Regression Analysis ◽  
In Situ Hybridization ◽  
Univariate Analysis ◽  
Figo Stage ◽  
Clinicopathological Parameters ◽  
Cox Regression Analysis ◽  
Endocervical Adenocarcinoma ◽  
Hpv E6 ◽  
Mrna In Situ Hybridization

Abstract Background Human papillomavirus (HPV) E6/E7 mRNA in situ hybridization (HPV E6/E7 RNAscope) appears to be a sensitive and specific technique in detecting transcriptionally active HPV. We aimed to examine the diagnostic utility of this technique in endocervical adenocarcinoma (ECA), to explore the prognostic factors for ECA patients and develop a clinically useful nomogram based on clinicopathological parameters to predict it. Methods We retrospectively analyzed 200 patients with ECA who had undergone surgery at Sun Yat-sen University Cancer Center from 2010 and 2014. The diagnostic performance of HPV E6/E7 RNAscope were evaluated by receiver operating characteristic (ROC) curve. A prognostic nomogram model including HPV E6/E7 RNAscope was generated based on multivariate Cox regression analysis, then we compared the predictive accuracy of the prognostic model with FIGO staging and treatment using concordance index (C-index), time-dependent ROC (tdROC), and decision curve analysis (DCA). Results The sensitivity and specificity of HPV E6/E7 RNAscope for distinguishing HPV-associated adenocarcinoma (HPVA) from non-HPV-associated adenocarcinoma (NHPVA) in the whole cohort were 75.8% and 80%, respectively. According the univariate analysis and multivariate logistic regression analysis, age, lymphovascular invasion (LVI), lymph node involvement (LNI), and HPV E6/E7 RNAscope were valuable predictive factors for OS. These parameters were incorporated into the nomogram model (nomogram A) compared with FIGO stage and treatment. The C-index of nomogram A for predicting OS was 0.825, which was significantly higher than FIGO stage (C-index = 0.653, p = 0.002) and treatment (C-index = 0.578, p < 0.001). Conclusions  HPV E6/E7 RNAscope is highly specific for ECA, and the 4-variable nomogram showed more accurate prognostic outcomes in patients with ECA.

A combined ultrastructural and gene molecular research for the relationship between human uterine cervical carcinoma and human papillomavirus

1990 ◽  
Vol 48 (3) ◽  
pp. 204-205
Author(s):  
Kun Lee ◽  
Jingyi Si ◽  
Ricai Han ◽  
Wei Zhang ◽  
Bingbing Tan ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Human Papillomavirus ◽  
Intraepithelial Neoplasia ◽  
Hpv Infection ◽  
Dot Blot ◽  
Homologous Sequences ◽  
Normal Cervical Epithelium ◽  
The Relationship ◽  
Chronic Cervicitis

There are more supports for the view that human papillomavirus (HPV) infection might be an etiological factor in the development of cervical cancer when the association of persistent condylomata is considered. Biopsies from 318 cases with squamous cell carcinoma of uterine cervix, 48 with cervical and vulvar condylomata, 14 with cervical intraepithelial neoplasia (CIN), 34 with chronic cervicitis and 24 normal cervical epithelium were collected from 5 geographic regions of China with different cervical cancer mortalities. All specimens were prepared for Dot blot, Southern blot and in situ DNA-DNA hybridizations by using HPV-11, 16, 18 DNA labelled with 32P and 3H as probes to detect viral homologous sequences in samples. Among them, 32 cases with cervical cancer, 27 with condyloma and 10 normal cervical epitheliums were randomly chosen for comparative EM observation. The results showed that: 1), 192 out of 318 (60.4%) cases of cervical cancer were positive for HPV-16 DNA probe (Table I)

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