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Review
. 2020 May 1;9(5):1305.
doi: 10.3390/jcm9051305.

Association of Salivary Human Papillomavirus Infection and Oral and Oropharyngeal Cancer: A Meta-Analysis

Óscar Rapado-González  1   2   3 , Cristina Martínez-Reglero  4 , Ángel Salgado-Barreira  4 , Almudena Rodríguez-Fernández  5 , Santiago Aguín-Losada  6 , Luis León-Mateos  6 , Laura Muinelo-Romay  2   3 , Rafael López-López  3   6 , María Mercedes Suarez-Cunqueiro  1   3   7
Affiliations
Review

Association of Salivary Human Papillomavirus Infection and Oral and Oropharyngeal Cancer: A Meta-Analysis

Óscar Rapado-González et al. J Clin Med. .

Abstract

Background: Human papillomavirus (HPV) infection has been recognized as an important risk factor in cancer. The purpose of this systematic review and meta-analysis was to determine the prevalence and effect size of association between salivary HPV DNA and the risk of developing oral and oropharyngeal cancer.

Methods: A systematic literature search of PubMed, EMBASE, Web of Science, LILACS, Scopus and the Cochrane Library was performed, without language restrictions or specified start date. Pooled data were analyzed by calculating odds ratios (ORs) and 95% confidence intervals (CIs). Quality assessment was performed using the Newcastle-Ottawa Scale (NOS).

Results: A total of 1672 studies were screened and 14 met inclusion criteria for the meta-analysis. The overall prevalence of salivary HPV DNA for oral and oropharyngeal carcinoma was 43.2%, and the prevalence of salivary HPV16 genotype was 27.5%. Pooled results showed a significant association between salivary HPV and oral and oropharyngeal cancer (OR = 4.94; 2.82-8.67), oral cancer (OR = 2.58; 1.67-3.99) and oropharyngeal cancer (OR = 17.71; 6.42-48.84). Significant associations were also found between salivary HPV16 and oral and oropharyngeal cancer (OR = 10.07; 3.65-27.82), oral cancer (OR = 2.95; 1.23-7.08) and oropharyngeal cancer (OR = 38.50; 22.43-66.07).

Conclusions: Our meta-analysis demonstrated the association between salivary HPV infection and the incidence of oral and oropharyngeal cancer indicating its value as a predictive indicator.

Keywords: human papillomavirus; meta-analysis; oral cancer; oropharyngeal cancer; saliva.

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Conflict of interest statement

R.L.-L. reports other from Nasasbiotech, during the conduct of the study; grants and personal fees from Roche, grants and personal fees from Merck, personal fees from AstraZeneca, personal fees from Bayer, personal fees and non-financial support from BMS, personal fees from Pharmamar, personal fees from Leo, outside the submitted work. The rest of the authors have nothing to disclose.

Figures

Figure 1
Figure 1
Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) flow diagram of the literature selection process, including identification, screening, eligibility and total studies included in qualitative and quantitative synthesis.
Figure 2
Figure 2
Schematic drawing of salivary HPV and prevalence of oral and/or oropharyngeal cancer. Oral tissue sheds pathogen-infected cells containing different HPV DNA genotypes (HPV16, HPV18, HR-HPV, and LR-HPV) into saliva (with or without oral rinses). The prevalence of salivary HPV DNA varied according to anatomic tumor location, showing the highest infection rate in oropharyngeal carcinomas. In addition, the type-specific prevalence in saliva was also different according to the anatomic tumor location.
Figure 3
Figure 3
Forest plot for the studies on the association between salivary HPV and oral and oropharyngeal cancer. The squares indicate the ORs (odds ratios) in each study, with square sizes inversely proportional to the standard error of the OR. The diamond shape indicates the pooled ORs. Horizontal lines represent 95% CIs (confidence intervals), I2 > 50% indicates severe heterogeneity.
Figure 4
Figure 4
Funnel plot for studies (of 14 studies) on the association between salivary HPV and oral and oropharyngeal cancer. The vertical line represents the pooled OR using random-effect meta-analysis. Two diagonal lines represent (pseudo) 95% confidence limits around the OR for each standard error on the vertical axis. In the absence of heterogeneity, 95% of the studies should lie within the funnel defined by these diagonal lines. Abbreviations: se OR, standard error of odds ratio.
Figure 5
Figure 5
Forest plot for the studies on the association between salivary HPV and oral and oropharyngeal cancer. The squares indicate the ORs in each study, with square sizes inversely proportional to the standard error of the OR. The diamond shape indicates the pooled ORs. Horizontal lines represent 95% CIs. I2 > 50% indicates severe heterogeneity. (a) HPV16, (b) HPV18, (c) HR-HPV, and (d) LR-HPV.
Figure 6
Figure 6
Forest plot for the studies on the association between salivary HPV and anatomic tumor subsites. The squares indicate the ORs in each study, with square sizes inversely proportional to the standard error of the OR. The diamond shape indicates the pooled ORs. Horizontal lines represent 95% CIs. I2 > 50% indicates severe heterogeneity. (a) Oral Cancer and (b) Oropharyngeal Cancer.
Figure 7
Figure 7
Forest plot for the studies on the association between salivary HPV and oropharyngeal cancer. The squares indicate the ORs in each study, with square sizes inversely proportional to the standard error of the OR. The diamond shape indicates the pooled ORs. Horizontal lines represent 95% CIs. I2 > 50% indicates severe heterogeneity. (a) HPV16, (b) HPV18, (c) HR-HPV, and (d) LR-HPV.
Figure 8
Figure 8
Forest plot for the studies on the association between salivary HPV and oral cancer. The squares indicate the ORs in each study, with square sizes inversely proportional to the standard error of the OR. The diamond shape indicates the pooled ORs. Horizontal lines represent 95% CIs. I2 > 50% indicates severe heterogeneity. (a) HPV16, (b) HPV18, (c) HR-HPV, and (d) LR-HPV.
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