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Background:
Systematic Review

Global Prevalence and Modifiers of Human Papillomavirus Positivity in Oral Cavity Cancer: A Systematic Review and Meta-Analysis of Prevalence (1995–2024)

by
Areeb Iraqui
†,
Alaa Safia
*,†,
Mohamad Mahameed
,
Uday Abd Elhadi
and
Shlomo Merchavy
Department of Otolaryngology, Head & Neck Surgery Unit, Ziv Medical Center, 1311001 Safed, Israel
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Cancers 2025, 17(17), 2870; https://doi.org/10.3390/cancers17172870
Submission received: 7 August 2025 / Revised: 25 August 2025 / Accepted: 30 August 2025 / Published: 31 August 2025
(This article belongs to the Section Systematic Review or Meta-Analysis in Cancer Research)
Browse Figures
Review Reports Versions Notes

Simple Summary

Oral cavity cancer is a serious disease affecting thousands of people worldwide. While a virus called human papillomavirus (HPV) is known to play a major role in throat cancers, its role in oral cavity cancers is still unclear. We reviewed and analyzed data from over 16,000 patients across 122 studies to better understand how often HPV is found in oral cavity cancers and whether this depends on age, gender, tumor site, or region. We found that HPV is present in about one in four cases, but the rates vary widely across countries and patient groups. These findings suggest that HPV may play a role in some—but not all—oral cancers. Our study highlights the importance of further research and consistent testing methods to better understand how HPV affects cancer in the mouth and how this knowledge can improve prevention and treatment strategies.

Abstract

Background/Objectives: Human papillomavirus (HPV) is a known etiologic agent in oropharyngeal cancers, but its role in oral cavity squamous cell carcinoma (OCSCC) remains unclear. This systematic review and meta-analysis aimed to estimate the global prevalence of HPV in OCSCC and explore variation by clinicodemographic and tumor characteristics. Methods: We systematically searched multiple databases for studies reporting HPV prevalence in OCSCC. Pooled prevalence estimates were calculated, and subgroup analyses examined differences by age, gender, cancer stage, anatomical site, histologic subtype, region, and HPV type (HPV-16 and HPV-18). Heterogeneity and publication bias were assessed using standard meta-analytic techniques. Results: A total of 122 studies involving 16,311 patients were included. The pooled HPV prevalence in OCSCC was 25.8% (95% CI: 20.4–31.2), with HPV-16 and HPV-18 detected in 52.4% and 30.3% of positive cases, respectively. Prevalence varied geographically, from 73% in Singapore to 7.7% in South Korea. Younger patients (<40 years) had higher HPV positivity (29.7%) than older patients (>70 years, 23.8%). Early-stage cancers (stage I) showed higher HPV prevalence (41.8%) than advanced-stage cancers (stage IV, 10.4%). Verrucous carcinoma had the highest HPV positivity (34.1%), and moderately differentiated tumors the lowest (23.4%). HPV prevalence was highest in the lower alveolus (29.5%) and lips (25%), and lowest in the upper gingiva (3.9%). Conclusions: HPV prevalence in OCSCC demonstrates significant heterogeneity across regions and clinical subgroups. These findings emphasize the need for standardized diagnostic approaches and further research into the role of HPV in OCSCC pathogenesis and treatment.

1. Introduction

Human papillomavirus (HPV) is a well-recognized etiological agent in a variety of cancers, including cervical, anogenital, and head and neck cancers [1]. Among head and neck cancers, HPV’s role is well-established in oropharyngeal squamous cell carcinoma (OPSCC) [2], where its presence is associated with distinct clinical and biological characteristics, including improved prognosis and responsiveness to treatment. However, the contribution of HPV to oral cavity squamous cell carcinoma (OCSCC) remains less clear and continues to be a subject of scientific debate [3,4].
The global burden of oral cavity cancer is significant, accounting for approximately 300,000 new cases annually [5]. While traditional risk factors such as tobacco use, alcohol consumption, and poor oral hygiene predominate, recent evidence suggests a role for high-risk HPV subtypes, particularly HPV-16 and HPV-18, in the pathogenesis of OCSCC [6]. Unlike OPSCC, the prognostic and therapeutic implications of HPV positivity in OCSCC are inconsistent, with studies reporting conflicting associations between HPV status and clinical outcomes [7].
The existing literature highlights substantial variability in HPV prevalence across geographic regions, patient demographics, and tumor characteristics, reflecting differences in HPV detection methods and population exposures [8,9,10,11,12,13,14]. Notably, the prevalence of high-risk HPV subtypes in OCSCC is often lower than in OPSCC, raising questions about the biological significance of HPV in oral carcinogenesis [14,15,16,17]. Furthermore, the interplay between HPV and other etiological factors, such as smoking and alcohol use, remains poorly understood.
In this context, a comprehensive understanding of the prevalence of HPV and its subtypes in OCSCC is critical to refining prevention, diagnosis, and treatment strategies. This systematic review and meta-analysis aim to quantify the global prevalence of HPV in OCSCC and explore its variability based on clinicodemographic factors, including age, gender, cancer stage, tumor site, and histological type. By synthesizing data from a diverse array of studies, we seek to elucidate the role of HPV in OCSCC and its implications for clinical and public health practices.

2. Materials and Methods

2.1. Design and Literature Search

The study protocol of this systematic review was registered on PROSPERO (CRD42024615069). This work was conducted following the PRISMA [18] (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) and AMSTAR [19] (Assessing the methodological quality of systematic reviews) guidelines. We searched PubMed, Scopus, Web of Science, the Cochrane Library, and Google Scholar (first 200 records) [20] up to 17 October 2024. The search strategy, outlined in Table S1, was adjusted for each database. Citations were filtered based on their titles and abstracts. No restrictions were applied regarding the original language of publication. Manual searches were conducted by reviewing reference lists and related articles on PubMed [21] and Google Scholar.

2.2. Selection Strategy

Studies were selected using the PECO (Population, Exposure, Comparison, and Outcomes) framework [22].
The inclusion criteria were as follows:
  • Population: patients with histologically confirmed oral cavity cancer.
  • Exposure: none.
  • Comparison: none.
  • Outcome: HPV-positive rate.
  • Study Design: epidemiological studies and cross-sectional studies. Case-control studies were only considered if they investigated the rate of HPV positivity in cancer and healthy individuals.
The exclusion criteria included the following:
  • Non-original research.
  • Abstract-only publications.
  • Experimental and investigation studies (clinical trials).
  • Case reports and case series.
  • Case-control studies including HPV-positive and HPV-negative controls.
  • Duplicated records or studies with overlapping datasets (similar samples and baseline characteristics even if author lists differed).
  • Non-oral cavity cancer (like oropharyngeal cancer—OPC).
  • Studies including patients with oral cavity cancer and OPC without stratifying HPV data based on cancer location.
  • Studies not reporting HPV-positivity rate.
  • Animal studies plus in vivo or in vitro studies.

2.3. Data Collection and Outcomes

The senior author designed the data collection sheet using Microsoft Excel. The sheet was modified multiple times to fit the data reported by the included studies. The final sheet comprised four parts. The first covered study-related data (authors’ names, year of publication/investigation, country of investigation, study design, and sample size). The second covered patient-related data (including age, gender, site of cancer, management type, and diagnostic method of both HPV and oral cavity cancer). The third part included the outcome data. The primary outcome was the prevalence of HPV positivity—overall and across various strains, specifically HPV-16 and -18 since they carry the highest risk. Exploratory/secondary analyses were conducted across various subsets of patients based on age group, gender, smoking status, alcohol intake, cancer site, management type, tumor stage (pathological and clinical), histopathological grading, and p16 immunohistochemistry (as a potential surrogate for HPV-positive cancers). A complete list of definitions used in this study can be found in the Supplementary Files. The fourth part included a methodological quality assessment.
To avoid double counting, we screened for potential cohort overlap across studies by cross-checking institution and location, recruitment years, author teams, and detection methods. When two reports could represent the same or partially overlapping series, we prioritized the report with the broader or more informative dataset and only retained a second report if it contributed an independent time window or unique subgroup data with its own denominator.

2.4. Risk of Bias Assessment

For all of the included studies, the National Institute of Health (NIH) tool was used. This tool assesses the methodological quality of observational studies through 14 questions, each of which can be given a score of 0, 1, or 2. This provides an overall quality score of good (score > 20), fair (score 11–20), and poor (score < 11). This scoring method has been previously employed widely and validated.

2.5. Statistical Analysis

All analyses were performed using STATA (Version 18, StataCorp LLC, College Station, TX, USA) following the a priori analysis plan. To account for the highly heterogeneous samples included in the quantitative synthesis, a random effects method was employed using the restricted maximum likelihood method (REML) to minimize the risk of missing data [23]. Heterogeneity was quantified using the I2 statistic, with significant heterogeneity defined as I2 > 40% [24].
Separate analyses were conducted for overall HPV and for specific HPV strains (HPV-11, -16, -18, -26, -33, -35, -52, -58, -65, and other strains). Since the HPV-16 and HPV-18 strains carry the most significant risks of cancer, they were analyzed and reported as secondary outcomes. For certain strains (HPV-2, -6, -16E, and -16Af-1/2) data were insufficient for analysis. Subgroup analyses were then performed to determine country-, year-, patient-, and cancer-specific changes in prevalence of HPV positivity.
Sensitivity analyses tested the robustness of results, with Galbraith plots identifying outliers, and publication bias was assessed with funnel plots and asymmetry tests [25]. No changes were observed with sensitivity analyses and no significant risks of publication bias were noted.

3. Results

3.1. Literature Search Results

The systematic literature search identified 6170 records across multiple databases (Figure 1). After removing 2578 duplicate records, 3591 unique records were screened for eligibility. Following an initial title and abstract screening, 2809 records were ruled out. A total of 782 full-text reports were sought for retrieval, with 48 reports not accessible. Of the 734 full-text reports assessed for eligibility, 587 were excluded for various reasons, including lack of prevalence data (n = 213), focus on oropharyngeal rather than oral cavity cancer (n = 80), absence of stratified data for oral cavity cancer (n = 103), and publication formats not suitable for data extraction (e.g., abstract-only publications, review articles, editorials, and case series; n = 216). An additional 40 reports were excluded for overlap with the original search results. Ultimately, 122 studies met the inclusion criteria and were incorporated into the meta-analysis [8,9,10,11,13,14,15,16,17,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76,77,78,79,80,81,82,83,84,85,86,87,88,89,90,91,92,93,94,95,96,97,98,99,100,101,102,103,104,105,106,107,108,109,110,111,112,113,114,115,116,117,118,119,120,121,122,123,124,125,126,127,128,129,130,131,132,133,134,135,136,137,138].

3.2. Baseline Characteristics

The included studies’ characteristics are summarized in Table 1. A total of 122 studies (97 cross-sectional and 25 case-control) investigated 16,311 patients with oral cancer, of whom 9528 (58.41%) males and 4177 (25.61%) females were examined. Overall HPV prevalence was reported in 120 (98.36%) of studies, with various subtypes being investigated as well, including HPV-16 (64, 52.45%), HPV-18 (37, 30.33%), HPV 11 (7, 5.74%), HPV-26 (3, 2.46%), HPV-33 (5, 4.09%), HPV-35 (3, 2.46%), HPV-52 (3, 2.46%), HPV-58 (8, 6.56%), and HPV-65 (1, 0.82%). Other strains were examined in 35 studies (28.69%); however, these strains were not classified and thus, were not investigated. Most evidence stemmed from India (24, 19.67%), followed by Thailand (7, 5.74%), Italy (6, 4.92%), and Japan (6, 4.92%). HPV-related data were available for various patients’ clinicodemographic data, including age (115 studies), gender (66 studies), smoking status (33 studies), alcohol intake (26 studies), cancer site (51 studies), TNM staging (25 studies), histological type (38 studies), p16 positivity (13 studies), and management type (29 studies). Data on specific cancer locations and HPV diagnosis can be found in Table 1.

3.3. Methodological Quality

A full description of the methodological quality of the included studies is provided in Table S2. Out of 122 studies, the majority had an overall fair methodological quality (92 studies, 75.41%), while the remaining 30 studies (24.59%) had an overall good quality, with no studies having a poor rating.

3.4. Country- and Year-Specific Prevalence Rates

The overall positivity of HPV in oral cancer showed variable rates over time, with the highest rate being reported in 1995 (73.6%; 95% CI: 64.6–82.7) and the lowest rate in 2024 (7.5%; 95% CI: 1.9–13.1). A negative trend can be observed over time (Figure 2) despite the increasing body of evidence in later years (2014–2024) compared to earlier periods (1995–2014). Time was a significant moderator of HPV prevalence (p = 0.001), with heterogeneity measures being reported in Table S3.
Figure 3 shows the differences in HPV prevalence across various countries, with Singapore showing the highest rates (73%; 95% CI: 64.6–82.7) followed by Venezuela (60%; 95% CI: 46.4–73.6), the Czech Republic (55.7%, 95% CI: 46.5–65), Saudi Arabia (52.4%; 95% CI: 0–99.4), and Malaysia (51.4%; 95% CI: 41.9–61). Meanwhile, South Korea (7.7%; 95% CI: 3.3–10.6), Greece (5.4%, 95% CI: 0–15.3), and the Netherlands (4.3%, 95% CI: 0–9.4) had the lowest rates. Complete, country-based prevalence data can be found in Table S4.

3.5. Age- and Gender-Specific Prevalence

Age-specific prevalence rates show that HPV positivity tended to be highest in younger patients, with a steady reduction in rate as patients age. For instance, patients <40 years had a prevalence rate of 29.7% (95% CI: 20.3–39%) followed by 40–60 years (25.4%; 95% CI: 19.8–30.9%), 60–70 years (24.3%; 95% CI: 17.4–31.3%), and >70 years (23.8%; 95% CI: 8.6–39.1%) (Table 2). Meanwhile, female patients (24.6%; 95% CI: 19.3–29.8) had slightly higher, but non-significant, rates of HPV positivity compared to male patients (23.5%; 95% CI: 18.8–28.2, p = 0.059).

3.6. Smoking- and Alcohol-Specific Prevalence

The prevalence of HPV positivity in oral cancer was highest in current smokers, accounting for 27.2% (95% CI: 18.4–36%) of cases, comparable to that of those who never smoked (25.4%; 95% CI: 18.1–32.8%). Surprisingly, former smoking was associated with the lowest rate of 9.4% (95% CI: 0–19, I2 = 0%).
On the other hand, the rate of HPV positivity in oral cancer was similar across patients who reported ever (current plus past drinkers) (22.7%; 95% CI: 14.9–30.4) or never drinking alcohol (21.8%; 95% CI: 13.9–29.8). Strikingly, patients who reported excessive drinking habits (not defined) exhibited the lowest rates of HPV positivity (12.2%; 95% CI: 7.2–17.2); however, this finding was based only on a single observation.

3.7. Cancer Site-Specific Prevalence

Twenty-one oral cancer sites were examined, with the most frequently investigated sites being oral tongue (51 studies), buccal mucosa (39 studies), floor of mouth (38 studies), hard palate (24 studies), gingiva (20 studies), and lips (19 studies). Complete site-specific data can be found in Table 2. HPV positivity was highest in the lower alveolus (29.5%; 95% CI: 0–76.5%) followed by the lips (25%; 95% CI: 14.7–35.3%), mandibular (24.6%; 95% CI: 3.3–45.9) and maxillary gingiva (23.1%; 95% CI: 8.9–37.2), oral tongue (22.7%; 95% CI: 16.7–28.7), buccal mucosa (20.9%; 95% CI: 14.2–27.6), hard palate (18.9%; 95% CI: 10.8–26.9), and lower gingiva (18.8%; 95% CI: 2.3–35.3). Meanwhile, the gingivobuccal sulcus (4.7%; 95% CI: 0–13), upper gingiva (3.9%; 95% CI: 0–10.5), and vestibulum of mouth (0.4%; 95% CI: 0–1.5) exhibited the lowest rates.

3.8. Cancer Stage- and Grade-Specific Prevalence

Cancer staging was conducted using AJCC, pathological TNM, and clinical TNM staging systems. The prevalence of HPV positivity was highest in stage II (36.4%) followed by stage III (32.3%), stage I (31.9%), and stage IV (29.1%). Early-stage cancer (I–II) showed higher prevalence compared to advanced stages (III–IV) (28.8% vs. 27.7%).
These findings did not align with those of clinical TNM staging. For instance, the prevalence of HPV positivity was highest in the earlier stages with steady and progressive decline in advanced stages (stage I = 41.8%; stage II = 27.7%; stage III = 12.4%; stage IV = 10.4), with early stages having almost double the rate of advanced stages (I–II vs. III–IV = 24% vs. 12.7%).
Surprisingly, the prevalence rates were lower according to the AJCC staging system. For instance, the prevalence of HPV positivity in stages I to IV were 7.8%, 3.3%, 3.9%, and 10.3%, respectively.
In terms of histological grade, the highest prevalence of HPV was observed with verrucous carcinoma (34.1%; 95% CI: 3.9–64.4) followed by well-differentiated carcinoma (26.8%; 95% CI: 19.6–34) and poorly differentiated cancer (26.7%; 95% CI: 18.7–34.7). Meanwhile, moderately differentiated cancer accounted for the lowest rate of 23.4% (16.8–30).

3.9. Tumor Size (T Staging) and Nodal Involvement-Based Prevalence

The rates of HPV positivity were quite similar across different tumors sizes (Table 2). For instance, the rate in T1–T2 stages was 25% compared to 25.9% in T3–T4 stages. A similar observation was noted for nodal involvement, where node-positive cancer had a rate of 16.8% compared to 17.9% for node-negative cancer. Meanwhile, the N2 stage had the highest prevalence rate of 24% while N3b had the lowest rate of 2.6%.

3.10. Treatment-Specific Prevalence

Significant variability in the prevalence of HPV positivity was observed for different treatment options (p = 0.001). Standalone chemotherapy was associated with the highest rate of HPV positivity (12.6%) followed by standalone radiotherapy (12%), surgery with radiotherapy (12%), and surgery with chemoradiation (9.2%). Meanwhile, treatment-naïve patients had the lowest rate of 3% (95% CI: 0–8.1).

3.11. P16-Specific Prevalence

The HPV-positive rate was higher in P16-positive patients (26.7%; 95% CI: 13.3–40%) compared to P16-negative patients (7.2%; 95% CI: 3.1–11.4%). However, this difference did not reach statistical significance (p = 0.151).

3.12. Subgroup Analyses Based on HPV-16 and HPV-18 Strains

Year- and country-specific differences in HPV prevalence between HPV-16 and HPV-18 strains are illustrated in Figure 4 and Figure 5. Although a declining trend can be observed in the prevalence of both strains over time, HPV-16 showed a mildly higher positivity rate than HPV-18 across most years. Additionally, HPV-16 showed higher positivity rates compared to the HPV-18 strain across most countries except for Japan, where HPV-18 showed predominance (37.4% vs. 10.2%).
The analysis revealed several significant differences in HPV-16 and HPV-18 positivity rates across clinicodemographic factors in oral cavity cancer patients (Tables S5–S7 and Figure 6). Among patients aged less than 40 years, HPV-16 positivity was significantly higher at 42.2% (95% CI: 22.2–62.3) compared to HPV-18 positivity at 26.8% (95% CI: 7.5–46.1). Conversely, in patients aged over 70 years, HPV-18 positivity was markedly higher at 50% (95% CI: 23.8–76.2) compared to HPV-16 positivity at 14.7% (95% CI: 0–37.4). In clinical TNM staging, HPV-16 exhibited a much higher positivity rate in stage I cancers, at 96.9% (95% CI: 88.3–100), compared to HPV-18 at 3.1% (95% CI: 0–11.7). However, in stage III cancers, HPV-18 positivity was significantly higher at 38.5% (95% CI: 12–64.9) compared to HPV-16 at 15.4% (95% CI: 0–35).
In terms of anatomical site, HPV-16 showed significantly higher positivity in cancers of the floor of the mouth at 50% (95% CI: 25.5–74.5), compared to HPV-18 at 33.3% (95% CI: 0–71.1). Conversely, in maxillary gingiva cancers, HPV-18 positivity was higher at 15.4% (95% CI: 0–35) compared to HPV-16 at 7.7% (95% CI: 0–22.2). For histological differentiation, poorly differentiated cancers exhibited slightly higher HPV-16 positivity at 36.5% (95% CI: 23.3–49.7) compared to HPV-18 at 31.4% (95% CI: 8.3–54.5). However, in moderately differentiated cancers, HPV-18 positivity was significantly higher at 39.1% (95% CI: 11.7–66.5) compared to HPV-16 at 26.8% (95% CI: 18.2–35.5). For pathological TNM staging in stage IV cancers, HPV-18 positivity was substantially higher at 50% (95% CI: 21.7–78.3) compared to HPV-16 at 16.7% (95% CI: 0–37.8). Similar positivity rates for HPV-16 and HPV-18 were observed across other patient clinicodemographic data and categories.

4. Discussion

4.1. Overview of Findings

This review synthesizes global evidence on the prevalence of HPV positivity in OCSCC and its variation across populations, time periods, detection methods, and clinicopathological strata. The pooled estimates and subgroup patterns highlight substantial heterogeneity that is partly methodological (assay and case definition) and partly epidemiological (region and case-mix). We focus the discussion on interpreting these drivers and their implications for practice and research, without revisiting the general background on OPSCC.

4.2. HPV Prevalence in Oral Cavity Cancer: A Global and Temporal Perspective

The prevalence of HPV positivity in oral cavity cancers demonstrated marked geographic variability, with the highest rates observed in Singapore, Venezuela, and the Czech Republic and the lowest in South Korea, Greece, and the Netherlands. These differences may be attributable to variation in risk factor exposures, healthcare access, and methodological inconsistencies across studies. The observed negative temporal trend, with declining HPV positivity rates in more recent years, might reflect improvements in tobacco and alcohol cessation programs or enhanced public health awareness about HPV vaccination, particularly in countries with robust vaccination programs [139,140,141].
This divergence from the rising HPV attribution observed in oropharyngeal cancer is likely explained, at least in part, by improved anatomic compartmentalization (reducing misclassification of tonsillar/base-of-tongue tumors as “oral cavity”) and assay standardization that together deflate earlier OCSCC estimates and yield lower, more specific recent rates. Detection methodology has shifted from heterogeneous p16-only surrogacy toward DNA/RNA-based testing and combined algorithms with more stringent positivity criteria. Simultaneously, better site assignments (distinguishing oral cavities from the oropharynx) have reduced historical misclassification. Both changes would bias calendar time trends downward for OCSCC and counsel caution against attributing the decline solely to changes in oral HPV exposure.

4.3. Age and Gender Differences in HPV Positivity

The prevalence of HPV showed significant age-related trends, with younger patients (<40 years) exhibiting the highest rates, which gradually declined with advancing age. This may indicate a potential role for recent changes in sexual behavior and HPV exposure patterns, particularly among younger cohorts. Although female patients exhibited slightly higher HPV positivity rates compared to males, this difference did not reach statistical significance. These findings align with prior research indicating gender parity in HPV-related oral cancers but underscore the need for targeted studies exploring potential gender-specific behavioral or biological susceptibilities [139,142,143].

4.4. HPV Subtype-Specific Prevalence: HPV-16 and HPV-18

This study highlights significant differences in the distribution of HPV-16 and HPV-18 positivity rates across various clinicodemographic categories. HPV-16 positivity predominated in younger patients and earlier cancer stages, whereas HPV-18 was more prevalent in older individuals and advanced disease stages. These distinctions support the hypothesis that different HPV subtypes may influence cancer pathogenesis differently, potentially due to variations in oncogenic potential and host–virus interactions. Such findings are critical for designing subtype-specific diagnostic and therapeutic strategies [140,142].

4.5. Cancer Site and Stage-Specific Differences

HPV positivity rates were highest in cancers of the lower alveolus and lips, with significantly lower rates in the gingivobuccal sulcus and upper gingiva. This site-specific variation may reflect differences in epithelial susceptibility to HPV infection or local microenvironmental factors influencing viral persistence. Furthermore, stage-specific analyses revealed contrasting trends across staging systems, with clinical TNM staging indicating higher positivity in early stages, while pathological and AJCC staging showed reduced prevalence in earlier stages. These discrepancies highlight the complexities of staging HPV-associated cancers and emphasize the need for standardization in reporting and classification [3,4,143].

4.6. Methodological and Detection Challenges

Our findings underscore the challenges in HPV detection, particularly in oral cavity cancers. While p16 immunohistochemistry is widely used as a surrogate marker, its limitations in distinguishing transcriptionally active HPV warrant caution. Incorporating more robust methods, such as E6/E7 mRNA analysis, could enhance diagnostic accuracy and reduce misclassification bias. These methodological discrepancies likely contribute to the heterogeneity observed in HPV prevalence estimates and their associations with clinical outcomes [4,140,142,144].

4.7. Public Health and Clinical Implications

The declining prevalence of HPV positivity, coupled with significant geographic and subtype variability, has implications for public health policies, including HPV vaccination programs. The low HPV prevalence in certain regions underscores the importance of tailoring vaccination strategies and public awareness campaigns to local epidemiological contexts. Additionally, understanding subtype-specific differences may inform personalized therapeutic approaches and improve prognostic stratification for HPV-related oral cavity cancers [140,141,143].

4.8. Limitations and Future Directions

Although this study synthesizes data from a large number of studies, limitations persist, including potential over- or under-reporting biases, as some countries had numerous publications on this topic while other countries barely reported any data (like Middle Eastern countries), as well as the presence of limited data from certain regions. Additionally, data on other strains of HPV were not sufficient to run meaningful analyses. Furthermore, race is a known risk factor of oral cavity and other cancer types [145], and has been associated with HPV in the literature [12]. Unfortunately, only a few studies reported data based on various races/ethnic groups [42,120]. Future research should prioritize standardization in HPV detection and reporting, alongside longitudinal studies to assess temporal trends in HPV-related oral cancers. Additionally, the integration of genomic and transcriptomic analyses could elucidate the biological mechanisms underpinning HPV-mediated carcinogenesis.

5. Conclusions

This study highlights significant variations in HPV prevalence across geographic regions, patient demographics, cancer sites, and stages. The findings underscore the importance of tailored prevention and treatment strategies while identifying critical gaps in current research. Future efforts should focus on harmonizing methodologies and exploring the molecular underpinnings of HPV’s role in oral cavity cancer to advance clinical care and public health interventions.

Supplementary Materials

The following supporting information can be downloaded at https://www.mdpi.com/article/10.3390/cancers17172870/s1. Table S1. The detailed search criteria employed in the literature search [date of search: 9 October 2024]; Table S2. A summary of the methodological quality of included studies using the National Institute of Health quality assessment tool; Table S3. The prevalence of total HPV positivity in oral cancer patients stratified by the year of investigation; Table S4. The prevalence of total HPV positivity in oral cancer patients stratified by the country of investigation; Table S5. Year-specific differences in HPV-16 and HPV-18 positivity in oral cavity cancer patients; Table S6. Country-specific differences in positivity rates of HPV-16 and HPV-18 in oral cavity cancer patients; Table S7. Differences in HPV-16 and HPV-18 positivity rates across various patient groups.

Author Contributions

Conceptualization, A.S. and S.M.; methodology, A.S. and M.M.; software, M.M.; validation, A.S., M.M. and U.A.E.; formal analysis, A.S.; investigation, A.I. and M.M.; resources, A.S. and S.M.; data curation, A.I. and M.M.; writing—original draft preparation, A.I. and M.M.; writing—review and editing, A.S. and S.M.; visualization, A.I. and U.A.E.; supervision, A.S. and S.M.; project administration, A.S.; funding acquisition, S.M. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

The analyzed dataset was derived from data published in the literature; however, the full dataset can be shared by the corresponding author upon reasonable request.

Conflicts of Interest

The authors declare no conflicts of interest.

Abbreviations

The following abbreviations are used in this manuscript:
AJCCAmerican Joint Committee on Cancer
CIConfidence interval
DNADeoxyribonucleic acid
E6/E7Early genes 6 and 7 of HPV
FISHFluorescence in Situ Hybridization
HPVHuman papillomavirus
IHCImmunohistochemistry
I2I-squared
LDLinear dichroism
MDModerately differentiated
OPCOropharyngeal cancer
OPSCCOropharyngeal squamous cell carcinoma
OROdds ratio
OSOverall survival
P16Cyclin-dependent kinase inhibitor 2A
PDPoorly differentiated
PECOPopulation, exposure, comparison, and outcomes
PRISMAPreferred Reporting Items for Systematic Reviews and Meta-Analyses
REMLRestricted maximum likelihood
RNARibonucleic acid
ROCReceiver operating characteristics
SCCSquamous cell carcinoma
TNMTumor, node, and metastasis
VCVerrucous carcinoma
WDWell differentiated

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Figure 1. A PRISMA flow diagram showing the results of the literature search and screening process.
Figure 1. A PRISMA flow diagram showing the results of the literature search and screening process.
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Figure 2. Trend analysis of HPV positivity in oral cavity cancer over time (1995–2024).
Figure 2. Trend analysis of HPV positivity in oral cavity cancer over time (1995–2024).
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Cancers 17 02870 g003
Figure 3. Country-specific prevalence of HPV positivity in oral cavity cancer.
Figure 3. Country-specific prevalence of HPV positivity in oral cavity cancer.
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Figure 4. Trend analysis of HPV-16 and HPV-18 positivity in oral cavity cancer over time (1995–2024). HPV—human papillomavirus.
Figure 4. Trend analysis of HPV-16 and HPV-18 positivity in oral cavity cancer over time (1995–2024). HPV—human papillomavirus.
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Figure 5. Country-specific prevalence of HPV-16 and HPV-18 positivity in oral cavity cancer. HPV—human papillomavirus; USA—United States of America.
Figure 5. Country-specific prevalence of HPV-16 and HPV-18 positivity in oral cavity cancer. HPV—human papillomavirus; USA—United States of America.
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Figure 6. Differences in the prevalence of HPV-16 and HPV-18 positivity based on various patients’ clinicodemographic characteristics. HPV—human papillomavirus; WD—well-differentiated; VC—verrucous cancer; PD—poorly differentiated; MD—moderately differentiated.
Figure 6. Differences in the prevalence of HPV-16 and HPV-18 positivity based on various patients’ clinicodemographic characteristics. HPV—human papillomavirus; WD—well-differentiated; VC—verrucous cancer; PD—poorly differentiated; MD—moderately differentiated.
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Table 1. Baseline characteristics of included studies estimating the prevalence of HPV positivity in oral cancer patients (n = 122).
Table 1. Baseline characteristics of included studies estimating the prevalence of HPV positivity in oral cancer patients (n = 122).
Author (YOP)CountryYear of InvestigationDesignSample SizeCancer Location (Number)Diagnostic Method (HPV)AgeGender
MeanSDMaleFemale
De Abreu (2018) [54]Brazil2012–2015Cross-sectional90Tongue (49), FOM (22), Other (19)Nested PCR using MY09/MY11 and GP5+/GP6+ primers57.912.736822
Abreu (2020) [26]UK2011–2015Prospective cohort99Tongue (72), FOM (9)ISH60.513.37722
ADAMOPOULOU (2008) [27]Germany2008Cross-sectional102Oral cavity cancer (68)PCR protocol52.110.35151
Adilbay (2018) [28]Kazakhistan2015–2017Prospective cohort76Oral cavity cancer (42)PCR protocol57.211.455026
Afzal (2019) [29]Pakistan2018–2019Cross-sectional140Oral cavity cancer (140)PCR protocol48.869.3711426
Ahmed (2019) [30]Iraq2019Cross-sectional80Oral cavity cancer (40)PCR protocol--2416
Ajila (2021) [31]India2021Case-control60Oral cavity cancer (30)PCR protocol588.86255
Akhondnezhad (2018) [32]Iran2006–2016Cross-sectional83Oral cavity cancer (83)PCR protocol46.215.54340
Ali (2008) [33]Pakistan1991–2004Retrospective cohort140Oral cavity (86), tongue (54)PCR protocol/primers GP5/650138258
Alsharif (2021) [34]Germany2002–2011Cross-sectional280Not specifiedISH62.81218892
Vidal Loustau (2019) [136]Switzerland2001–2011Retrospective cohort155Mobile tongue (61)PCR protocol66.513.6310748
Antuncov (2022) [35]Montenegro2012–2018Cross-sectional60Tonge (22), FOM (10), lower lip (28)PCR protocol6210.54713
Anwar (2024) [36]Pakistan2017Cross-sectional186Not specifiedPCR protocol----
Ashraf (2017) [37]Iran2017Case-control100Oral tongue SCC (50)nested PCR53.5411.194159
Balaram (1995) [38]Singapore1995Cross-sectional91Oral cavity (91)PCR protocol----
Belobrov (2017) [39]Australia2007–2011Prospective cohort46Tongue (20), FOM (5), check mucosa (5), Mandibular Alveolus (2)Laser capture microdissection--2620
Bijina (2020) [41]India2020Case-control90Oral cavity (47)PCR protocol, gel electrophoresis5514.967020
Boy (2006) [42]South Africa1998–2003Cross-sectional59Oral cavity (59)ISH/signal enhancement (Genpoint)/PCR57.588.414118
Božinović (2020) [43]Serbia2005–2006Cross-sectional63Tonsil (13), Tongue (9)ISH54.74.63924
Campisi (2006) [44]Italy2006Cross-sectional63Not specifiedPCR protocol68.8911.782835
Chakrobarty (2014) [45]India2006–2008Case-control183Oral cancer (83)PCR protocol50.8110.5613647
Chen (2012) [46]Taiwan2003–2004Cross-sectional65Tongue (35), buccal mucosa (20), gingiva (2), hard palate (1), FOM (7)ISH54.310.885213
Chen (2016) [47]China2016Cross-sectional99Oral cavity cancer (40)PCR protocol56.7-355
Chotipanich (2018) [48]Thailand2018Case-control208Oral cavity (52)PCR protocol6011.715454
Chowdary (2018) [49]India2018Case-control40Oral cavity (20)PCR protocol--2416
Cutilli (2016) [50]Italy1992–2012Retrospective cohort75Not specifiedPCR protocol673.155718
DAHLGREN (2004) [51]Sweden1970–2002Cross-sectional110Mobile tongue (85), base of tongue (25)PCR protocol/primers GP5/662.4612.726941
D’Costa (1998) [53]India1998Cross-sectional100Buccal (57), tongue (14), FOM (2)PCR protocol51.312.27228
Dhanapal (2015) [57]India2015Cross-sectional23Buccal mucosa (8), FOM (2), tongue (1)PCR protocol61.56.577
Duncan (2013) [59]USA2002–2007Cross-sectional81Tongue (36), FOM (11), buccal mucosa (4), lip (2)PCR protocol/IHC63.912.574437
Elango (2011) [60]India2004–2007Case-control106Oral tongue cancer (60)PCR protocol, IHC, ISH53.8713.327630
Emmett (2017) [62]Australia2006–2012Cross-sectional63Tongue (48), FOM (14), Oral cavity (1)PCR protocol60.7134716
Emmett (2018) [61]Australia2018Cross-sectional136Oral cavity (40)PCR protocol--11323
Nola-Fuchs (2012) [95]Croatia2012Case-control54Not specifiedSwab53.910.1459
Gan (2014) [63]China2009–2013Case-control268Not specifiedPCR protocol----
Giovannelli (2006) [64]Italy2004Cross-sectional116Oral cavity (17)PCR protocol58.912.754967
Goto (2023) [66]Japan2009–2013Cross-sectional67Tongue (34), FOM (5)PCR protocol--5413
Götz (2016) [67]Germany2009–2011Cross-sectional202Not specifiedIHC57.5810.2314557
Ha (2022) [69]Maryland1982–2000Cross-sectional102Oral cavity (34)PCR protocol5915.58517
Harbor (2024) [70]South Africa2009–2019Cross-sectional50Lip (50)HybriSpot
HPV Direct Flow Chip kit		61143812
Huang (2012) [72]Taiwan1997–2003Cross-sectional103Tongue (60), lip (1), mouth floor (6)PCR protocol94.410.9967
Huang (2017) [71]Taiwan2017Cross-sectional85Not specifiedPCR protocol--787
Ibieta (2005) [8]Mexico1999–2001Cross-sectional50Tongue (13), mouth of floor (4)PCR protocol--3614
Ishibashi (2011) [73]Japan2011Cross-sectional107Oral cavity (50)PCR protocol/using consensus primers
(My09/My11, GP5?/GP6?)		59.213.725750
Jaber (2019) [74]Saudi Arabia2010–2014Retrospective cohort45Not specifiedISH60.25-2421
JALOULI (2010) [75]India2010Cross-sectional74Tongue (18), buccal (12), lip (6)PCR protocol55.310.75915
Jalouli (2012) [76]Sweden2012Cross-sectional155Tongue (41), FOM (23)PCR protocol63.3---
JitAni (2015) [77]India2010–2013Cross-sectional31Not specifiedPCR protocol/ISH--1615
Kaminagakura (2012) [78]Brazil1970 to 2006Case-control114Tongue (23), buccal (1)PCR protocol/IHC345.48333
KANSKY (2003) [9]Slovenia1994–1998Case-control124Oral cavity (62)PCR protocol58.27.3557
Grewal (2018) [68]India2011–2014Cross-sectional47Tongue (23), lip (4), buccal (9)nested PCR--3611
Khanna (2009) [79]India2007–2009Case-control120Not specifiedPCR protocol50.6-9030
Khovidhunkit (2008) [80]Thailand2008Cross-sectional65Buccal mucosa (11)PCR protocol58.2213.061550
Kim (2018) [81]South Korea2010–2015Retrospective cohort187Tongue (54), gum (80)DNA chip kit6411.911671
Klozar (2008) [82]Czech Republic2001–2005Cross-sectional81Tonsil (51), oral (10), tongue (4), base of tongue (10)PCR protocol--5130
Komolmala (2020) [10]Thailand1999–2019Cross-sectional403Tongue (46), FOM (8)PCR protocol66-7894
Kouketsu (2015) [83]Japan2012–2013Cross-sectional174Tongue (90), gingiva (43), buccal (22), FOM (7), lip (11)PCR protocol67.612.77698
Kulkarni (2011) [84]India2009–2010Cross-sectional490Oral cavity (34)PCR protocol----
Bhawal (2007) [40]Japan2007Cross-sectional22Oral cavity (22)PCR protocol/PT-PCR66.612.6139
Lee (2012) [85]Taiwan2004–2006Prospective cohort333Not specifiedPCR protocol--31617
Lee (2015) [86]Taiwan2004–2011Retrospective cohort1002Tongue (322), lip (35), FOM (31)PCR protocol--93864
Liang (2008) [87]China2004–2006Cross-sectional51Oral tongue (51)PCR protocol59.512.43120
Lukesova (2014) [88]Czech Republic2014Cross-sectional60Oral cavity (5)PCR protocol56.5-546
Machado (2010) [11]Canada1995–2007Retrospective cohort92Oral cavity, tongue, FOM, palate, buccal mucosa and gingiva (53)PCR protocol--6428
Makvandi (2022) [15]Iran2013–2019Cross-sectional166Oral tongue (140), base of tongue (22), tonsils (4)Nested PCR53.2315.914422
Matzow (2009) [89]Sweden2009Cross-sectional54Tongue (11), FOM (7), gingiva (10), buccal (2)PCR protocol----
De Menezes (2022) [55]Brazil2019Cross-sectional101Tongue (19), lip (16), gingiva (46)PCR/”Inno-Lipa Genotyping Extra II System--4655
Montaldo (2010) [90]Italy2007–2008Case-control120Not specifiedPCR protocol61.713.37248
More (2020) [91]Saudi Arabia2020Cross-sectional45Oral cavity (30)PCR protocol--3114
NAGPAL (2001) [92]India2001Case-control110Tongue (6), lip (4)PCR assay--6842
Naqvi (2020) [93]Pakistan2015–2017Cross-sectional58Tongue (17), lip (11), buccal mucosa (24)PCR protocol42124810
Nauta (2021) [94]The Netherlands2008–2014Retrospective cohort940Tongue (451), FOM (268)PCR protocol64.8612551389
Nekić (2022) [16]Croatia2022Retrospective cohort99Oral cavity (26)PCR protocol--8910
OLIVEIRA (2003) [96]Brazil2008Retrospective cohort87Tongue (22), lip (13)PCR protocol--7314
Ostwald (2003) [97]Germany2003Cross-sectional267Intraorally (93), lips (21)PCR protocol58.57-18681
PALMIER (2011) [98]Italy1990–2007Case-control278Oral cavityRT-PCR----
Panneerselvam (2019) [99]India2019Cross-sectional30Not specifiedPCR protocol46.7-273
Panzarella (2021) [100]Italy2021Cross-sectional40Not specifiedPCR protocol66.514.11723
Parshad (2015) [101]India2015Prospective cohort50Tonsil (15), base of tongue (16)PCR protocol55.3210.2446
Patel (2015) [102]India2015Cross-sectional149Tongue (21), buccal (39)PCR protocol48.310.88465
Premoli-De-Percoco (2001) [108]Venezuela2001Cross-sectional50Tongue (18), buccal mucosa (7), FOM (7)PCR protocol56.3-050
Petito (2017) [103]Brazil2005–2007Cross-sectional82Oral cavity (39)PCR protocol--6418
Petrovic (2023) [13]Serbia2018–2022Cross-sectional90Tongue (19), lip (4), buccal (4)PCR protocol62.95-4842
Phusingha (2016) [104]Thailand2005–2010Case-control191Tongue (20), lip (16), FOM (16)Reverse line blot hybridization (RLBH)--11576
POLZ (2010) [106]Poland1998–2004Cross-sectional60Oral cavity (21)PCR protocol57.5-546
Polz-Gruszka (2015) [107]Poland2006–2009Retrospective cohort154Oral cavity (92)PCR protocol56.88.813123
Pongsapich (2016) [17]Thailand2010–2012Cross-sectional46Not specifiedPCR protocol59.615.162917
Ravi Prakash (2024) [111]India2020–2022Retrospective cohort100Not specifiedISH or PCR.58.758.17426
Purwanto (2019) [109]Indonesia2003–2013Cross-sectional78Tongue (58), lip (6), buccal (2)PCR protocol47.0814.154731
Rahbarnia (2019) [110]Iran2012–2014Case-control60Tongue (30)PCR protocol61.313.72634
González-Ramírez (2013) [65]Mexico2007–2011Case-control400Tongue (47), palate (11), buccal (1), Gingival (21)PCR protocol----
Delgado Ramos (2018) [56]Ecuador2006–2011Cross-sectional53Tongue (100%)PCR protocol61.817.32924
Rivero (2006) [112]Brazil2006Cross-sectional40Lip (20), Tongue (14), gingiva (3), FOM (2) and palate (1)PCR protocol5713.6328
Rodríguez-Santamarta (2016) [113]Spain1996–2007Retrospective cohort125Tongue (51), FOM (37), buccal (7)PCR protocol/ ISH58.614.48243
ROMANITAN (2008) [14]Greece1986–2007Cross-sectional115Tonsil (31), tongue (38)PCR protocol627.9--
Rout (2024) [114]India2024Cross-sectional140Not specifiedPCR protocol54.5-11723
Rungraungrayabkul (2022) [115]Thailand2013–2019Retrospective cohort81Tongue (24) buccal mucosa (11) lip (5)PCR protocol--3249
Saini (2010) [116]Malaysia2010Case-control210Tongue (29), lip (1)GP5+/GP6+ in a nested PCR49.1213.4109101
Schwartz (2001) [117]USA1988–1995Cross-sectional254Tongue (81), tonsil (44)PCR protocol54.2-16391
Shima (2000) [118]Japan1991–1996Cross-sectional46Tongue (27), buccal (3), FOM (3)PCR protocol50143214
Sichero (2024) [119]brazil2015–2019Cross-sectional146Oral cavity (89)PCR protocol--11828
Simonato (2008) [120]Brazil1991–2005Cross-sectional29Not specifiedPCR protocol/GP5+⁄GP6+ (35)--272
Singh (2015) [122]India2013–2015Prospective cohort250Buccal mucosa (127), FOM (4)Real-Time PCR, Conventional PCR/IHC--20050
Singh (2016) [121]India2013–2014Prospective cohort43Not specifiedPCR protocol45.5610.04376
Smith (1998) [123]USA1994–1996Case-control298Not specifiedPCR protocol--198100
Soares (2007) [124]Brazil2000–2003Cross-sectional75Tongue (20), FOM (17), lips (14)PCR protocol65.4513.24926
Sri (2021) [125]India2010–2012Cross-sectional40Not specifiedQiagen QIAamp
DNA tissue Kit (Qiagen Inc., USA).		----
Dirasantchu (2015) [58]India2015Case-control35Buccal mucosa (10), tongue (5), alveolus (4), retromolar (3), buccal sulcus (1)PCR protocol--2411
Taberna (2017) [126]USAJuly 1905Prospective cohort262Oral cavity (90)ISH--21349
Tachezy (2005) [127]Czech Republic2000–2003Cross-sectional68Tongue (5), tonsil (8)PCR protocol57-5414
Tang (2020) [128]The Netherlands2020Cross-sectional183Not specifiednested PCR--11865
Tangthongkum (2024) [129]Thailand2012–2021Retrospective cohort381Not specifiedPCR protocol--232149
Tealab (2009) [130]Egypt2008–2015Retrospective cohort99tongue (48), lip (45)PCR protocol/ISH57.2135544
Tokuzen (2021) [131]Japan2004–2013Cross-sectional100Tongue (36), mandibular gingiva (31), maxillary gingiva (13), FOM (9), buccal mucosa (9), or lower lip (2)RT-qPCR68.210.085446
Dalla Torre (2018) [52]Australia2008–2012Retrospective cohort106Not specifiedPCR protocol58.97.97135
TSIMPLAKI (2014) [132]Greece2012–2013Cross-sectional53Not specifiedPCR protocol5112.43914
Valls-Ontanón (2007) [133]Spain2010–2011Retrospective cohort155Tongue (47), buccal (11), lip (8)PCR protocol72.713.410748
Vanshika (2021) [134]India2018–2019Cross-sectional216Not specified(RT-PCR)45.6-17244
Pintos Vega (2002) [105]Canada1997–2001Case-control201Tongue except base (21), FOM (12), lips (1)PCR protocol/DNA sequencing62.7-14358
Verma (2018) [135]India2018Case-control100Tongue (16), buccal (12). lip (3)PCR47.696.73--
Yang (2019) [137]China2016–2017Case-control163Tongue (70), buccal (40), FOM (3)IHC81.5127687
Zhang (2004) [138]China1997–1999Case-control113Tongue (35), buccal (14), FOM (10)PCR protocol--7241
YOP—year of publication; YOI—year of investigation; SD—standard deviation; USA—United States of America; UK—United Kingdom; PCR—polymerase chain reaction; IHC—Immunohistochemical Staining; ISH—in situ hybridization; RT-PCR—real-time PCR.
Table 2. The prevalence of HPV positivity in oral cavity cancer stratified by patients’ clinical/cancer characteristics and management type.
Table 2. The prevalence of HPV positivity in oral cavity cancer stratified by patients’ clinical/cancer characteristics and management type.
GroupPrevalence (%)95% CIStudiesQp-ValueTau2I2 (%)H2
Gender
Female24.619.3–29.8651022.390.0000.03896.3927.71
Male23.518.8–28.2661201.370.0000.03596.8431.63
Age
<4029.720.3–392075.320.0000.02681.455.39
40–6025.419.8–30.961812.970.0000.04395.1520.61
60–7024.317.4–31.326242.160.0000.02791.4311.67
>7023.88.6–39.1842.020.0000.03790.7810.85
Smoking
Current27.218.4–3631584.640.0000.05897.5841.28
Ever23.34.1–42.47126.020.0000.06497.539.95
Former9.40–1941.870.5990.00001
Never25.418.1–32.833297.040.0000.03993.9816.62
Alcohol
Ever22.714.9–30.424207.950.0000.03294.8119.26
Excessive12.27.2–17.210.00 0.000
Never21.813.9–29.826254.810.0000.03695.6823.15
Histological Type
MD23.416.8–3038542.570.0000.03796.6129.48
PD26.718.7–34.737257.320.0000.03988.899
VC34.13.9–64.4422.090.0000.08090.8810.97
WD26.819.6–3436659.140.0000.04397.1234.75
AJCC
I7.80–15.820.170.6760.00001
II3.30–8.230.950.6220.00001
III3.90–9.230.470.7910.0000.011
IV10.35.5–15.130.310.8590.0000.011
Site
Lip2514.7–35.31979.630.0000.03478.074.56
Lower Lip14.86–23.651.430.8380.00001
Upper Lip16.70–58.810.00 0.000
Gingiva18.210.9–25.52064.750.0000.01883.76.14
Lower Gingiva18.82.3–35.322.10.1470.00752.492.1
Upper Gingiva3.90–10.530.810.6650.00001
Mandibular Gingiva24.63.3–45.9512.930.0120.03567.333.06
Maxillary Gingiva23.18.9–37.244.050.2560.00001
Alveolus24.50–56.1426.890.0000.09491.5311.81
Lower Alveolus29.50–76.5332.680.0000.16697.9849.6
Upper Alveolus7.10–26.210.00 0.000
Oral Tongue22.716.7–28.751504.770.0000.04295.3821.67
Mobile Tongue11.20–24.1521.660.0000.01897.4338.92
Tongue Border17.10–34.920.160.6870.00001
Buccal Mucosa20.914.2–27.639423.850.0000.03693.4615.3
Floor of Mouth14.810.7–193891.970.0000.00766.442.98
Gingivobuccal sulcus4.70–1320.450.5040.00001
Hard Palate18.910.8–26.92454.40.0000.01961.982.63
Retromolar Trigone10.55–161731.820.0110.00445.641.84
Vestibulum of Mouth0.40–1.510.00 0.000
Waldeyer ring25.810.4–41.210.00 0.000
Pathological TNM
I31.919.7–44.218254.330.0000.06095.9824.9
II36.424.3–48.618194.610.0000.05992.8113.92
III32.320.1–44.517156.030.0000.05690.8810.97
IV29.117.3–40.815129.220.0000.04593.415.15
I–II28.819.1–38.425556.590.0000.05597.4739.6
III–IV27.719.3–36.123282.890.0000.03895.1420.59
Pathological T
T125.413.5–37.218224.660.0000.05697.8245.9
T225.915–36.819415.850.0000.05398.5669.44
T328.416.5–40.320241.490.0000.06696.1125.71
T425.914.9–3719312.680.0000.05296.0525.31
T1–T22515.8–34.125621.710.0000.05098.7479.1
T3–T425.916.8–35.125582.910.0000.05197.5440.6
Pathological N
N017.99.5–26.418291.310.0000.02997.0333.68
N+16.810.8–22.818153.190.0000.01390.4210.44
N118.35.5–31.11086.290.0000.03693.4215.2
N22415.4–32.5914.090.0790.00748.271.93
N2a11.70–40.622.670.1020.03162.522.67
N2b4.40–9.521.80.1800.00144.331.8
N2c92.6–15.420.180.6720.00001
N328.711.1–46.368.460.1320.01838.271.62
N3a16.70–58.810.00 0.000
N3b2.60–5.720.390.5340.00001
N416.70–46.510.00 0.000
Clinical TNM
I41.83.3–80.44193.140.0000.14697.5540.81
I–II245.6–42.510328.290.0000.08597.4839.61
II27.73.7–51.8529.470.0000.06794.0516.82
III12.41.7–23.146.940.0740.00656.972.32
III–IV12.78.5–16.81020.660.0140.00258.142.39
IV10.41.7–19.249.750.0210.00674.243.88
Clinical N
N0123.4–20.58144.060.0000.01397.7243.94
N+16.22.4–29.98158.240.0000.03898.2456.93
N181.4–14.7622.910.0000.00580.845.22
N29.82.9–16.7650.750.0000.00688.68.77
N370–23.431.730.4220.00713.791.16
Management
Chemoradiation10.56–1552.150.7090.0000.021
Chemotherapy12.66.2–1920.000.9800.00001
Radiotherapy121.2–22.9416.220.0010.00775.154.02
Surgery alone7.12.1–12.1652.120.0000.00393.9916.63
Surgery plus chemoradiation9.22.4–16519.630.0010.00479.24.81
Surgery plus radiotherapy124.1–19.9524.70.0000.00686.217.25
Treatment-naïve30–8.120.340.5590.00001
P16 Positivity
Negative7.23.1–11.41355.190.0000.00482.665.77
Positive26.713.3–4013154.280.0000.05095.1520.6
MD—moderately differentiated; WD—well-differentiated; PD—poorly differentiated.
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Iraqui, A.; Safia, A.; Mahameed, M.; Abd Elhadi, U.; Merchavy, S. Global Prevalence and Modifiers of Human Papillomavirus Positivity in Oral Cavity Cancer: A Systematic Review and Meta-Analysis of Prevalence (1995–2024). Cancers 2025, 17, 2870. https://doi.org/10.3390/cancers17172870

AMA Style

Iraqui A, Safia A, Mahameed M, Abd Elhadi U, Merchavy S. Global Prevalence and Modifiers of Human Papillomavirus Positivity in Oral Cavity Cancer: A Systematic Review and Meta-Analysis of Prevalence (1995–2024). Cancers. 2025; 17(17):2870. https://doi.org/10.3390/cancers17172870

Chicago/Turabian Style

Iraqui, Areeb, Alaa Safia, Mohamad Mahameed, Uday Abd Elhadi, and Shlomo Merchavy. 2025. "Global Prevalence and Modifiers of Human Papillomavirus Positivity in Oral Cavity Cancer: A Systematic Review and Meta-Analysis of Prevalence (1995–2024)" Cancers 17, no. 17: 2870. https://doi.org/10.3390/cancers17172870

APA Style

Iraqui, A., Safia, A., Mahameed, M., Abd Elhadi, U., & Merchavy, S. (2025). Global Prevalence and Modifiers of Human Papillomavirus Positivity in Oral Cavity Cancer: A Systematic Review and Meta-Analysis of Prevalence (1995–2024). Cancers, 17(17), 2870. https://doi.org/10.3390/cancers17172870

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