Prevalence of Human Papillomavirus in Oropharyngeal Cancer: A Systematic Review

Abstract

Purpose: The global incidence of oropharyngeal squamous cell carcinoma (OPSCC) has been increasing, and it has been proposed that a rising rate of human papillomavirus (HPV)-associated cancers is driving the observed changes in OPSCC incidence. We carried out this systematic review to further examine the prevalence of HPV in OPSCC over time worldwide.

Methods: A systematic literature search was performed to identify all articles through January 31, 2014, which reported on the prevalence of HPV in OPSCC. Articles that met the inclusion criteria were divided into 4 time frames (pre-1995, 1995-1999, 2000-2004, and 2005 to present) based on the median year of the study's sample collection period. Using a weighted analysis of variance model, we examined the trends of HPV-positivity over time worldwide, in North America, and in Europe.

Results: Our literature search identified 699 unique articles. One hundred seventy-five underwent review of the entire study, and 105 met the inclusion criteria. These 105 articles reported on the HPV prevalence in 9541 OPSCC specimens across 23 nations. We demonstrated significant increases in the percentage change of HPV-positive OPSCCs from pre-1995 to present: 20.6% worldwide (P for trend: P < 0.001), 21.6% in North America (P = 0.013), and 21.5% in Europe (P = 0.033).

Conclusions: Interestingly, whereas in Europe there was a steady increase in HPV prevalence across all time frames, reaching nearly 50% most recently, in North America HPV prevalence appears to have plateaued over the past decade at about 65%. These findings may have important implications regarding predictions for the future incidence of OPSCC.

Figure 1. Flow chart of article inclusion and exclusion

Diagram depicting the article accrual process as well as the inclusion and exclusion of studies from this systematic review.

Figure 2. HPV prevalence in OPSCC by region

Scatterplots depicting the raw HPV prevalence values for each article within the three main regions analyzed: worldwide, North America and Europe. The relative size of each grey circle is dependent on the number of OPSCCs evaluated by the study. The year for each article represents the median year of sample collection. The blue line plot represents the mean values for HPV prevalence in OPSCC generated by our statistical model for each region across four different time frames: pre-1995, 1995—1999, 2000—2004, and 2005—present.

Figure 3. Frequency of HPV-positive OPSCCs worldwide, in North America and across Europe

Shaded maps representing the prevalence of HPV-positive OPSCCs in each region within a specified time frame. As the map's color shifts from yellow to orange to red, the prevalence of HPV is increasing. Documented below each map is the number of articles analyzed, total number of OPSCCs evaluated and the pooled mean HPV prevalence value and associated 95% confidence interval for that specific region and time frame. *p<0.05, **p<0.01.

Figure 4. Prevalence of HPV in OPSCC for individual countries

All studies with a median year for their sample collection period from 2000—present were included in this analysis. The total number of OPSCCs and HPV-positive OPSCCs were summed from all articles within an individual nation. These values were used to determine the proportion of HPV-associated cancers along with a 95% confidence interval, which is depicted for each country in this plot. Counties not classified as advanced economies by the International Monetary Fund are indicated by a $.