The integration of HR-HPV increases the expression of cyclins A and E in cytologies with and without low-grade lesions

Zubillaga-Guerrero, Ma Isabel; Illades‐Aguiar, Berenice; Leyva‐Vázquez, Marco Antonio; Flores‐Alfaro, Eugenia; Castañeda-Saucedo, Eduardo; Muñoz-Valle, J.F.; Alarcón-Romero, L C

doi:10.4103/0970-9371.107504

Cited by 8 publications

(9 citation statements)

References 29 publications

(32 reference statements)

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“…Integration of the viral genome into the cancer cell genome is a characteristic of the infection by these HPVs. 23 , 24 Other types of HPV, such as low-risk (L-R) or non-oncogenic HPV6 and HPV11, induce benign ano-genital warts and are rarely found in ano-genital malignancies. 25 The HPV DNA has been detected in tumor tissues of head and neck cancers, 26 oral cancers, 27 esophageal cancers, 28 and some skin cancers, 29 as well as lung cancers.…”

Section: Discussionmentioning

confidence: 99%

Detection of human papillomavirus infection by molecular tests and its relation to colonic polyps and colorectal cancer

Gazzaz

Mosli

Jawa

et al. 2016

SMJ

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Objectives:To prospectively examine the association between human papilloma virus (HPV) colonization of the colonic mucosa and the development of colorectal polyps (CRPs), and colorectal cancer (CRC) in Saudi Arabia.Methods:A case control study was performed between January 2013 and December 2014. All eligible patients underwent standard diagnostic colonoscopy. Patients with polyps or colorectal cancer were considered cases, while those with any other endoscopic findings were controls. Biopsy samples from polyps and tumors, and/or from normal colonic mucosa were acquired. Human papilloma virus colonization was detected using a hybrid capture technique of samples taken from both normal tissue, and CRPs and CRC. The association between HPV and CRPs/CRC was evaluated.Results:A total of 132 patients were recruited. The mean age was 53 (±15.9) years. Sixty patients had endoscopically detectable CRPs/CRC, and 72 had either inflammation or normal endoscopic evaluations. Only 4 (0.8%) of the 132 samples that were collected and analyzed were positive for the HPV gene. Statistical analysis did not identify any significant association between HPV colonization and the presence of CRPs/CRC. The only significant predictor of detecting CRPs/CRC on colonoscopy was symptomatic presentation (odds ratio=11.072, 95% confidence interval 4.7-26.2, p<0.001).Conclusion:Human papilloma virus colonic colonization is rare in Saudi Arabia. An association between HPV colonization and CRP/CRC development could not be identified in this cohort of patients.

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Section: Discussionmentioning

confidence: 99%

Detection of human papillomavirus infection by molecular tests and its relation to colonic polyps and colorectal cancer

Gazzaz

Mosli

Jawa

et al. 2016

SMJ

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“…Nucleic acid amplification and hybridization techniques are used to detect the presence and physical status of viral DNA [ 3 ]. On the other hand, immunodetection techniques can be used to evaluate the levels of cellular proteins involved in cell cycle such as p16ink4a and Ki-67 [ 4 ], cyclins [ 5 ], MCM2 and TOPIIA [ 6 ], Temolerase [ 7 ], which are markers of HPV infection-associated alterations. Nonetheless, these immunomarkers do not distinguish between transient and persistent (carcinogenic) HPV infections [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

Ezrin and E-cadherin expression profile in cervical cytology: a prognostic marker for tumor progression in cervical cancer

et al. 2018

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BackgroundCervical cancer (CC) is the fourth cause of mortality by neoplasia in women worldwide. The use of immunomarkers is an alternative tool to complement currently used algorithms for detection of cancer, and to improve selection of therapeutic schemes. Aberrant expression of Ezrin and E-cadherin play an important role in tumor invasion. In this study we analyzed Ezrin and E-cadherin expression in liquid-based cervical cytology samples, and evaluated their potential use as prognostic immunomarkers.MethodsImmunocytochemical staining of Ezrin and E-cadherin was performed in cervical samples of 125 patients. The cytological or histological diagnostic was performed by Papanicolaou staining or H&E staining, respectively. HPV genotyping was determined using INNO-LIPA Genotyping Extra kit and the HPV physical status by in situ hybridization. Ezrin expression in HaCaT, HeLa and SiHa cell lines was determined by immunocytochemistry, immunofluorescence and Western blot.ResultsHigh Ezrin expression was observed in cervical cancer samples (70%), samples with multiple infection by HR-HPV (43%), and samples with integrated viral genome (47%). High Ezrin expression was associated with degree of SIL, viral genotype and physical status. In contrast, low E-cadherin expression was found in cervical cancer samples (95%), samples with multiple infection by HR-HPV/LR-HPV (87%) and integrated viral genome (72%). Low E-cadherin expression was associated with degree of SIL and viral genotype. Interestingly, Ezrin nuclear staining was associated with degree of SIL and viral genotype. High Ezrin expression, high percent of nuclear Ezrin and low E-cadherin expression behaved as risk factors for progression to HSIL and cervical cancer.ConclusionsEzrin and E-cadherin expression profile in cervical cytology samples could be a potential prognostic marker, useful for identifying cervical lesions with a high-risk of progression to cervical cancer.Electronic supplementary materialThe online version of this article (10.1186/s12885-018-4243-7) contains supplementary material, which is available to authorized users.

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“…HPV integration and the grade of cervical neoplasia may also be identified using a biotinyl tyramide-based in situ hybridization (ISH) method. Punctate signals within the nucleus are consistent with the integration of HPV into host cell chromosomes, whereas diffuse signal patterns throughout the nucleus are consistent with episomal DNA ( 30 – 33 ).…”

Section: Introductionmentioning

confidence: 73%

“…The chromogen 3,3′-diaminobenzidene (Dako; Agilent Technologies, Inc.) was then added and Mayer's hematoxylin (Merck KGaA, Darmstadt, Germany) at 37°C for 10 sec was used as a contrast dye. Positive reactions were visualized as brown inside of the nucleus in a LEICA DM 1000 light microscope and, according to the type of signal, were classified as diffuse (episomal state), punctate (integrated state) or diffuse and punctate (mixed state) ( 30 , 31 , 33 ). SiHa cell lines (containing HPV 16) were used as positive controls to demonstrate an integrated state; the same cell lines without probes were used as negative controls.…”

Section: Methodsmentioning

confidence: 99%

Methylation of the L1 gene and integration of human papillomavirus 16 and 18 in cervical carcinoma and premalignant lesions

et al. 2017

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High-risk human papillomavirus (HPV) is the primary cause of cervical carcinoma (CC). Viral integration into the host chromosomes is associated with neoplastic progression, and epigenetic changes may occur as a result. The objective of the present study was to analyze HPV L1 gene methylation and to compare the use of quantitative polymerase chain reaction (qPCR), in situ hybridization (ISH) and L1 methylation analysis as methods for detecting HPV integration. Cervical scrapes or biopsy samples positive for HPV 16 or 18, from 187 female patients with CC, squamous intraepithelial lesions (SILs) or no intraepithelial lesion (non-IL) were analyzed. Methylation of the L1 gene was determined using bisulfite modification followed by PCR, and HPV integration was subsequently analyzed. HPV 16 L1 gene methylation was revealed to increase with histological grade, with statistically significant differences observed as follows: Low-grade SIL vs. CC, P<0.0001 and non-IL vs. CC, P<0.0001. HPV 18 L1 gene methylation also increased according to histological grade, however, no statistically significant differences were observed. Methylation at CpG site 5608 of the HPV 16 L1 gene was associated with all grades of cervical lesions, whereas methylation at CpG site 5617 demonstrated the strongest association with CC (odds ratio, 42.5; 95% confidence interval, 4.7–1861; P<0.0001). The concordance rates between the various methods for the detection of the physical status of HPV 16 and HPV 18 were 96.1% for qPCR and ISH, 76.7% for qPCR and L1 gene methylation, and 84.8% for ISH and L1 gene methylation. In conclusion, methylation of the HPV 16 L1 gene increases significantly according to the grade of the cervical lesion, and methylation at CpG sites 5608 and 5617 of this gene may be used as prognostic biomarkers. ISH and L1 gene methylation have good concordance with qPCR with regards to the detection of HPV integration. Therefore, these are useful methods in determining the physical state of HPV.

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The integration of HR-HPV increases the expression of cyclins A and E in cytologies with and without low-grade lesions

Cited by 8 publications

References 29 publications

Detection of human papillomavirus infection by molecular tests and its relation to colonic polyps and colorectal cancer

Detection of human papillomavirus infection by molecular tests and its relation to colonic polyps and colorectal cancer

Ezrin and E-cadherin expression profile in cervical cytology: a prognostic marker for tumor progression in cervical cancer

Methylation of the L1 gene and integration of human papillomavirus 16 and 18 in cervical carcinoma and premalignant lesions

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