Characterization of cytomegalovirus and epstein‐barr virus infection in cervical lesions in Portugal

Marinho‐Dias, Joana; Ribeiro, Joana; Monteiro, Paula; Loureiro, Joana; Baldaque, Inês; Medeiros, Rui; Sousa, Hugo

doi:10.1002/jmv.23596

Cited by 12 publications

(12 citation statements)

References 27 publications

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“…Our results are consistent with a study conducted among women in Andhra Pradesh, India, where a relatively high level of CMV viral load was not correlated with a higher grade cervical precancerous lesions . In contrast, a study of Portuguese women found that while CMV was present at low frequency in the sample population, CMV viral expression was associated with an increased risk of CIS or ICC (22.2%), and of low‐grade lesions (9.5%), as compared with normal cytology (4.5%) …”

Section: Discussionsupporting

confidence: 90%

“…The prevalence of EBV infection was significantly higher in women with relatively higher grades of cervical disease among studies in India and Africa . Furthermore, both EBV encoding regions and EBV latent oncoproteins have been found in cervical tumor tissue . Taken together, these data suggest that EBV may be a marker for, or cofactor in, the etiology of high‐grade cervical precancer.…”

Section: Introductionmentioning

confidence: 82%

“…However, some studies have shown that EBV does not reside in the cervical epithelium but rather within infiltrating lymphoid cells adjacent to the tumor epithelium, potentially influencing the microenvironment . Although cellular localization of EBV remains contested, previous reports are in agreement that EBV can infect cervical tissues and potentially influence the risk of progression to high‐grade cervical lesions and cervical cancer …”

Section: Discussionmentioning

confidence: 99%

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Epstein‐Barr virus, but not human cytomegalovirus, is associated with a high‐grade human papillomavirus–associated cervical lesions among women in North Carolina

Kienka

Varga

Caves

et al. 2018

Journal of Medical Virology

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Statement of the problem Human papillomavirus (HPV) infection is known to contribute to cervical carcinogenesis, yet other cofactors that may contribute to oncogenesis are poorly understood. Herein, we examine whether the Epstein‐Barr virus (EBV) and human cytomegalovirus (CMV), two oncomodulatory viruses, are associated with HPV‐mediated cervical neoplastic progression. Methods Sixty patient cervical brush samples from a study of North Carolina women were obtained. HPV RNA positivity was determined by Aptima testing (Hologic Corporation, Marlborough, MA). The level of viral transcripts for EBV and CMV was quantified (reverse transcription polymerase chain reaction analysis), and the coinfection status with HPV was then compared with the patient's cervical cytology grade. Results Over one‐third (38.3%) of the study population was CMV positive, whereas 43.3% was EBV positive. When sample data were stratified by the cytology grade, 36.5% (19/52) of normal patients, 75% (3/4) of low‐grade squamous intraepithelial lesions (LSIL), and 100% (4/4) of patients with high‐grade SIL (HSIL) were EBV positive. Conversely, 35.2% (18/52) of normal patients, 25% (1/4) of patients with LSIL, and 50% (2/4) of patients with HSIL were CMV positive. When examining only HPV positive–associated HSIL, 100% (4/4) were positive for both HPV and EBV detection. This suggests that co‐viral detection with HPV and EBV is associated with more advanced HSIL cervical lesions, while CMV displayed no clear association with a higher grade of cervical cytology. Conclusions Co‐viral detection with EBV may increase the oncogenicity and/or serve as a viral marker of progression to HPV‐associated high‐grade cervical dysplasia.

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Section: Discussionsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 82%

Section: Discussionmentioning

confidence: 99%

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Epstein‐Barr virus, but not human cytomegalovirus, is associated with a high‐grade human papillomavirus–associated cervical lesions among women in North Carolina

Kienka

Varga

Caves

et al. 2018

Journal of Medical Virology

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“…In Portugal, there are very few studies regarding the prevalence of EBV either in different diseases or healthy individuals [Cabeda et al, ; Breda et al, ; Sousa et al, ; Magro et al, ; Marinho‐Dias et al, ]. To our knowledge, no study has examined the extent of genetic diversity of EBV in Portugal.…”

Section: Discussionmentioning

confidence: 99%

Characterization of Epstein–Barr virus strains and LMP1‐deletion variants in Portugal

Neves

Marinho‐Dias

Ribeiro

et al. 2015

Journal of Medical Virology

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Variations in the genome sequence of Epstein-Barr Virus (EBV) are thought to lead to differential interaction with host cells, immune evasion, and transformation. The discussion regarding EBV strains as having a geographic or disease-association has been increasing and the majority of studies are performed in Asiatic populations. We developed a case-control study with 139 individuals, including 96 subjects with different malignancies and 43 healthy individuals, from the North region of Portugal. We have used PCR protocols for the characterization of EBV strains (type A or B) based on EBNA3C genome variation and for the LMP1 30bp-deletion variants (wt-LMP1 or del-LMP1). Our study showed that type A is the most prevalent in our population (100% of healthy controls, 96.9% of aHSCT patients, 90.8% of HNSCC patients, and 94.9% of NPC patients) and that type B was significantly associated with NPC (P = 0.019; RR = 8.90). Regarding the LMP1 30bp-deletion, we found a similar distribution of both wt- and del-LMP1 variants in controls and dispare results in cases: del-LMP1 was more frequent in aHSCT and HNSCC patients (64.7% and 63.2%, respectively) and wt-LMP1 in NPC patients (100%). In fact, the study reveals that wt-LPM1 was significantly associated with NPC (P < 0.001; RR = 18.4). Hence, our study showed that EBV type B and wt-LMP1 variant seem to be associated with NPC in our population, with a clear disease-association for wt-LMP1. These results contribute for the knowledge of EBV genetic diversity among Caucasian populations.

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“…Nevertheless, HPVs are considered a necessary but not sufficient cause of HPV-associated cancers 4109110111 and a number of co-factors and risk-factors have been documented 112. These co-factors are represented by (i) coincident infectious agents such as EBV, HSV-2, HIV and Chlamydia 111113114115116117; (ii) environmental factors (various chemical agents, UV light, immune suppression, stress); (iii) behavioral factors (sexual partners, parity and smoking) and (iv) genetic and epigenetic factors (various polymorphisms in HLA molecules, p53 and GST 118119, the genetic predisposition known as epidermodysplasia verruciformis, and methylation status of the viral genome) (reviewed in 1120121). Several studies have indicated that cervical cancer development and progression may be closely associated with a dual-infection with HPV and EBV 4115.…”

Section: Epidemiology Incidence and Prevalencementioning

confidence: 99%

HPV disease transmission protection and control

Christensen¹

2016

MIC

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Human papillomaviruses (HPVs) represent a large collection of viral types associated with significant clinical disease of cutaneous and mucosal epithelium. HPV-associated cancers are found in anogenital and oral mucosa, and at various cutaneous sites. Papillomaviruses are highly species and tissue restricted, and these viruses display both mucosotropic, cutaneotropic or dual tropism for epithelial tissues. A subset of HPV types, predominantly mucosal, are also oncogenic and cancers with these HPV types account for more than 200,000 deaths world-wide. Host control of HPV infections requires both innate and adaptive immunity, but the viruses have developed strategies to escape immune detection. Viral proteins can disrupt both innate pathogen-sensing pathways and T-cell based recognition and subsequent destruction of infected tissues. Current treatments to manage HPV infections include mostly ablative strategies in which recurrences are common and only active disease is treated. Although much is known about the papillomavirus life cycle, viral protein functions, and immune responsiveness, we still lack knowledge in a number of key areas of PV biology including tissue tropism, site-specific cancer progression, codon usage profiles, and what are the best strategies to mount an effective immune response to the carcinogenic stages of PV disease. In this review, disease transmission, protection and control are discussed together with questions related to areas in PV biology that will continue to provide productive opportunities of discovery and to further our understanding of this diverse set of human viral pathogens.

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Characterization of cytomegalovirus and epstein‐barr virus infection in cervical lesions in Portugal

Cited by 12 publications

References 27 publications

Epstein‐Barr virus, but not human cytomegalovirus, is associated with a high‐grade human papillomavirus–associated cervical lesions among women in North Carolina

Epstein‐Barr virus, but not human cytomegalovirus, is associated with a high‐grade human papillomavirus–associated cervical lesions among women in North Carolina

Characterization of Epstein–Barr virus strains and LMP1‐deletion variants in Portugal

HPV disease transmission protection and control

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