E6/E7 mRNA Expression of the Most Prevalent High-Risk HPV Genotypes in Cervical Samples from Serbian Women

Nikolić, Nataša; Bašica, Branka; Mandić, Aljoša; Surla, Nela; Gusman, Vera; Medić, Deana; Štrbac, Mirjana; Petrović, Vladimir

doi:10.3390/diagnostics13050917

Cited by 10 publications

(16 citation statements)

References 67 publications

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“…While numerous new screening tools have been proposed for HPV detection, an effective approach for viral load testing detects mRNA of E6 and E7 transforming genes. 59 The E6/E7 mRNA expression might reflect the phase of HPV infection, and its positive pattern might also forecast the progression of CINs, thus efficiently improving the diagnostic sensitivity and specificity of cervical carcinoma and precancerous lesions, thereby avoiding over‐examination. Devices for self‐collection of urine which are licensed for gender neutral usage, have a high acceptance globally.…”

Section: Resultsmentioning

confidence: 99%

A comprehensive narrative review of challenges and facilitators in the implementation of various HPV vaccination program worldwide

Aggarwal,

Agarwal,

Gupta

2024

Cancer Medicine

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IntroductionCervical cancer has been considered as one of the most common cancers in women (15–44 years) globally, but the advent of the human papilloma virus (HPV) vaccine has raised the anticipation that eradication of cervical carcinoma might be achieved in the near future as several prophylactic cervical carcinoma vaccines have already been currently licensed in various countries. Countries should devise strategies, practices and policies to attain and sustain higher levels of HPV immunization coverage as still 68% countries have introduced HPV vaccine in their national immunization programs even after 17 years following the licensure of the first prophylactic HPV vaccine.MethodologyA comprehensive literature analysis was conducted using various databases and search engines, to include the most relevant research articles and data available and critically discussed the operational gaps that need to be answered to achieve adequate coverage of HPV vaccination.ResultsThe present review highlights the existing HPV vaccination strategies, unmet needs and challenges needed to be addressed for proper implementation framework as well as the collaborations required to achieve decent vaccination coverage. Well‐coordinated vaccination strategy with focus on adolescent girls and if possible, boys can lead to dramatic impact on disease reduction around the world.

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Section: Resultsmentioning

confidence: 99%

A comprehensive narrative review of challenges and facilitators in the implementation of various HPV vaccination program worldwide

Aggarwal,

Agarwal,

Gupta

2024

Cancer Medicine

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“…Sole p16ink4a immunostaining displayed lower sensitivity (41%) and specificity (86%) in LSIL women compared to dual staining [ 28 ]. In addition, HPV16 E7 mRNA expression has also been associated with cervical lesion progression to CIN2+ and holds potential as a diagnostic marker for HSIL [ 31 , 32 ].…”

Section: Discussionmentioning

confidence: 99%

“…However, in a region with a high prevalence of cervical cancer, the incidence of cervical cancer in an ASC-US cytology was 7.9% [ 22 ]. To minimize unnecessary colposcopy referrals, additional tests, in addition to hr-HPV tests were developed, such as p16ink4a immunostaining alone [ 28 ], or p16/ki67 dual staining [ 29 , 30 ], hr-HPV oncogene expressions [ 31 , 32 ], and DNA methylation [ 33 , 34 ].…”

Section: Introductionmentioning

confidence: 99%

Efficiency of CIN2+ Detection by Thyrotropin-Releasing Hormone (TRH) Site-Specific Methylation

Chaiwongkot,

Buranapraditkun,

Oranratanaphan

et al. 2023

Viruses

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Cervical cancer screening typically involves a Pap smear combined with high-risk human papillomavirus (hr-HPV) detection. Women with hr-HPV positivity but normal cytology, as well as those with precancerous abnormal cytology, such as low-grade squamous intraepithelial lesions (LSIL) and high-grade SIL (HSIL), are referred for colposcopy and histology examination to identify abnormal lesions, such as cervical intraepithelial neoplasia (CIN) and cervical cancer. However, in order to enhance the accuracy of detection, bioinformatics analysis of a microarray database was performed, which identified cg01009664, a methylation marker of the thyrotropin-releasing hormone (TRH). Consequently, a real-time PCR assay was developed to distinguish CIN2+ (CIN2, CIN3, and cervical cancer) from CIN2- (CIN1 and normal cervical epithelia). The real-time PCR assay utilized specific primers targeting methylated cg01009664 sites, whereas an unmethylated reaction was used to check the DNA quality. A cut-off value for the methylated reaction of Ct < 33 was established, resulting in improved precision in identifying CIN2+. In the first cohort group, the assay demonstrated a sensitivity of 93.7% and a specificity of 98.6%. In the cytology samples identified as atypical squamous cells of undetermined significance (ASC-US) and LSIL, the sensitivity and specificity for detecting CIN2+ were 95.0% and 98.9%, respectively. However, when self-collected samples from women with confirmed histology were tested, the sensitivity for CIN2+ detection dropped to 49.15%, while maintaining a specificity of 100%. Notably, the use of clinician-collected samples increased the sensitivity of TRH methylation testing. TRH methylation analysis can effectively identify women who require referral for colposcopy examinations, aiding in the detection of CIN2+.

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“…The samples collected during 2014, 2019, 2020, and 2021 were tested using the HPV High-Risk Typing Real-TM Kit (Sacace Biotechnologies, Como, Italy), which detects and genotypes twelve HR HPVs (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, and 59). A detailed protocol was previously described by Nikolic et al (2023) [18]. Samples collected during the other six years were tested using the HPV Genotypes 14 Real-TM Quant Real-Time PCR Kit (Sacace Biotechnologies, Como, Italy) to detect and genotype 14 HR HPVs (16,18,31,33,35,39,45,51,52,56,58,59, 66, and 68).…”

Section: Hr Hpv Detection and Genotypingmentioning

confidence: 99%

“…A detailed protocol was previously described by Nikolic et al (2023) [18]. Samples collected during the other six years were tested using the HPV Genotypes 14 Real-TM Quant Real-Time PCR Kit (Sacace Biotechnologies, Como, Italy) to detect and genotype 14 HR HPVs (16,18,31,33,35,39,45,51,52,56,58,59, 66, and 68). E1 gene (HPV 56), E6 gene (HPV 16,31,33,45,59, 66, and 68), E6/E7 gene (HPV 35), and E7 gene (HPV 18, 39, 51, 52, and 58) genotypes were amplified using primers and TaqMan probes in the four separate multiplex reactions each performed in a total volume of 25 µL.…”

Section: Hr Hpv Detection and Genotypingmentioning

confidence: 99%

Prevalence of Carcinogenic Genotypes of HPV-Infected Women in a Ten-Year Period (2014–2023) in Vojvodina, Serbia

Nikolic,

Basica,

Strbac

et al. 2024

Medicina

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Background and Objectives: Human papillomavirus (HPV) infection and its etiological role in the development of cervical cancer are well established. The cervical cancer mortality rate in Serbia is one of the highest among European countries, and this cancer is the second-leading cause of death in Serbian women aged from 15 to 44. Materials and Methods: This retrospective study was conducted at the Institute of Public Health of Vojvodina. A total of 10,062 cervical specimens from Serbian women were collected and HPV tested in ten years. The study patients were divided into five age groups. HPV genotype testing was performed using a commercial kit to detect 14 high-risk (HR) HPV genotypes. Additionally, cervix cytology data have been available for patients tested in 2022 and 2023. Results: An overall positive rate was found in 43.3% of patients (4356/10,062). A single HPV infection (62.1%) was the main infection pattern. The most frequent HR HPV genotypes were HPV 16, 31, 52, 56, 39, and 51, comprising 62.3% of the detected genotypes, including multiple infections. A significant difference was noted in the HPV prevalence across the different age groups, with a bimodal distribution of HPV infection. The highest prevalence was recorded in the age group ≤ 30 and those after 61 years. Women diagnosed with high-grade squamous intraepithelial lesions (HSIL) were significantly older compared to others. HR HPV is the most prevalent in patients with HSIL cytological findings (76.5%). The most common type, according to age-specific distribution and cytological findings, was HR HPV 16. Conclusions: This study provides comprehensive data on HR HPV distribution among Serbian women, which can serve as a basis for subsequent monitoring of genotypic distribution. It is particularly significant considering they are missing in the updated ICO/IARC Report for Serbia, and the cervical cancer mortality rate in Serbia is one of the highest among European countries.

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E6/E7 mRNA Expression of the Most Prevalent High-Risk HPV Genotypes in Cervical Samples from Serbian Women

Cited by 10 publications

References 67 publications

A comprehensive narrative review of challenges and facilitators in the implementation of various HPV vaccination program worldwide

A comprehensive narrative review of challenges and facilitators in the implementation of various HPV vaccination program worldwide

Efficiency of CIN2+ Detection by Thyrotropin-Releasing Hormone (TRH) Site-Specific Methylation

Prevalence of Carcinogenic Genotypes of HPV-Infected Women in a Ten-Year Period (2014–2023) in Vojvodina, Serbia

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