Unique role of HPV16 in predicting oropharyngeal cancer risk more than other oncogenic oral HPV infections

Fakhry, Carole; Fung, Nicholas; Tewari, Sakshi R.; D’Souza, Gypsyamber

doi:10.1016/j.oraloncology.2020.104981

Cited by 6 publications

(3 citation statements)

References 12 publications

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“…As also observed for the other HPV-associated cancers, HPV16 is by far the most frequent genotype in HPV-related OPSCCs [133][134][135]. Detection of HPV16 DNA in oral samples is associated with a 22-fold increased risk of developing an OPSCC [133] Compared to other High-risk types, the role of HPV16 in predicting OPSCC risk, thus seems to be unique [136].…”

Section: Oral Infection By Alpha Beta and Gamma Hpvs: The Clinical Aspectsmentioning

confidence: 76%

Human Papillomavirus Oral Infection: Review of Methodological Aspects and Epidemiology

et al. 2021

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Oral infection by Human Papillomavirus (HPV) has recently gained great attention because of its involvement in the development of a subset of head and neck squamous cell carcinoma. The role of specific Alpha-HPVs in this regard has been well established, whereas the contribution of other genera is under investigation. Despite their traditional classification as “cutaneous” types, Beta and Gamma HPVs are frequently detected in oral samples. Due to the lack of a standardized protocol, a large variety of methodologies have been used for oral sample collection, DNA extraction, HPV detection and genotyping. Laboratory procedures influence the evaluation of oral HPV prevalence, which largely varies also according to the population characteristics, e.g., age, gender, sexual behavior, Human Immunodeficiency Virus (HIV) status. Nevertheless, oral infection by Beta and Gamma HPVs seems to be even more common than Alpha-HPVs. The latter is 5–7% in the general population, and increases up to 30% approximately in HIV-infected men who have sex with men. Despite major advances in the evaluation of oral HPV prevalence, its natural history is still little understood, especially for Beta and Gamma HPVs. The latest technologies, such as Next Generation Sequencing (NGS), can be exploited to gain new insights into oral HPV, and to improve the identification of novel HPV types.

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Section: Oral Infection By Alpha Beta and Gamma Hpvs: The Clinical Aspectsmentioning

confidence: 76%

Human Papillomavirus Oral Infection: Review of Methodological Aspects and Epidemiology

et al. 2021

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“…The current evidence suggests that HPV16 is implicated in at least 85% of all HPV-OPC in the oropharynx [ 37 ]. Some studies have reported the prevalence of HPV in OPC to be as high as 97% [ 38 ]. In contrast, HPV16 is implicated in 52% of cervical cancers, followed by HPV18 in 18% of cases [ 39 ].…”

Section: Introductionmentioning

confidence: 99%

Surveillance of human papillomavirus through salivary diagnostics - A roadmap to early detection of oropharyngeal cancer in men

Wijesekera,

Weeramange,

Vasani

et al. 2024

Tumour Virus Research

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“…Of note, HPV16 represents the most common genotype (83%) among HPV-positive OPSCC patients [ 2 ]. Hence, HPV16 is by far the most carcinogenic HPV type in OPSCC, as most non-HPV16 oncogenic infections do not progress to cancer [ 3 ]. Although HPV confers a substantial survival benefit to these malignancies [ 4 ], roughly 20% of all patients with HPV-positive OPSCC develop recurrent disease within 5 years after diagnosis [ 5 – 8 ].…”

Section: Introductionmentioning

confidence: 99%

LINE-1 hypomethylation is associated with poor outcomes in locoregionally advanced oropharyngeal cancer

et al. 2022

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Background and purpose Currently, human papillomavirus (HPV) positivity represents a strong prognostic factor for both reduced risk of relapse and improved survival in patients with oropharyngeal squamous cell carcinoma (OPSCC). However, a subset of HPV-positive OPSCC patients still experience poor outcomes. Furthermore, HPV-negative OPSCC patients, who have an even higher risk of relapse, are still lacking suitable prognostic biomarkers for clinical outcome. Here, we evaluated the prognostic value of LINE-1 methylation level in OPSCC patients and further addressed the relationship between LINE-1 methylation status and p53 protein expression as well as genome-wide/gene-specific DNA methylation. Results In this study, DNA was extracted from 163 formalin-fixed paraffin-embedded tissue samples retrospectively collected from stage III-IVB OPSCC patients managed with curative intent with up-front treatment. Quantitative methylation-specific PCR revealed that LINE-1 hypomethylation was directly associated with poor prognosis (5-year overall survival—OS: 28.1% for LINE-1 methylation < 35% vs. 69.1% for ≥ 55%; p < 0.0001). When LINE-1 methylation was dichotomized as < 55% versus ≥ 55%, interaction with HPV16 emerged: compared with hypermethylated HPV16-positive patients, subjects with hypomethylated HPV16-negative OPSCC reported an adjusted higher risk of death (HR 4.83, 95% CI 2.24–10.38) and progression (HR 4.54, 95% CI 2.18–9.48). Tumor protein p53 (TP53) gene is often mutated and overexpressed in HPV-negative OPSCC. Since p53 has been reported to repress LINE-1 promoter, we then analyzed the association between p53 protein expression and LINE-1 methylation levels. Following p53 immunohistochemistry, results indicated that among HPV16-negative patients with p53 ≥ 50%, LINE-1 methylation levels declined and remained stable at approximately 43%; any HPV16-positive patient reported p53 ≥ 50%. Finally, DNA methylation analysis demonstrated that genome-wide average methylation level at cytosine–phosphate–guanine sites was significantly lower in HPV16-negative OPSCC patients who relapsed within two years. The subsequent integrative analysis of gene expression and DNA methylation identified 20 up-regulated/hypomethylated genes in relapsed patients, and most of them contained LINE-1 elements in their promoter sequences. Conclusions Evaluation of the methylation level of LINE-1 may help in identifying the subset of OPSCC patients with bad prognosis regardless of their HPV status. Aberrant LINE-1 hypomethylation might occur along with TP53 mutations and lead to altered gene expression in OPSCC.

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Unique role of HPV16 in predicting oropharyngeal cancer risk more than other oncogenic oral HPV infections

Cited by 6 publications

References 12 publications

Human Papillomavirus Oral Infection: Review of Methodological Aspects and Epidemiology

Human Papillomavirus Oral Infection: Review of Methodological Aspects and Epidemiology

Surveillance of human papillomavirus through salivary diagnostics - A roadmap to early detection of oropharyngeal cancer in men

LINE-1 hypomethylation is associated with poor outcomes in locoregionally advanced oropharyngeal cancer

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