Cancer is the second leading cause of death worldwide and a major global health burden. Worldwide estimates suggest that one in five people will develop cancer during their lifetime, contributing to high mortality rates. According to GLOBOCAN statistics for 2022, lung, breast, and colorectal cancers are the most prevalent malignancies worldwide.⁽¹⁾ Cancer also imposes a substantial burden on health systems because of the high costs associated with treatment, including hospitalization and palliative care.⁽²⁾ This disease has been associated with non-modifiable risk factors, such as genetic alterations, and modifiable risk factors, such as tobacco smoking, alcohol use, obesity, chronic inflammation, and infections.⁽³⁾ Beyond these well-recognized factors involved in the etiopathogenesis of malignant neoplasms, current evidence suggests that multiple biological mechanisms contribute to tumor development and progression.⁽⁴⁾

Among these mechanisms, evidence from in vitro and in vivo studies suggests that microorganisms may be involved in cancer progression.⁽⁵⁾ Bacterial cells may contribute to this process by modulating the host immune system and influencing tumor-related phenotypes.⁽⁵⁾ Within the human microbial ecosystem, the oral cavity harbors the second largest microbial community in the body, comprising more than 700 species, many of which have been associated with oral cancer and cancers at other body sites.^(6,7) Previous evidence has identified associations among alterations in the oral microbiome, increased colonization by microorganisms associated with periodontal diseases, such as Porphyromonas gingivalis,⁽⁸⁾ and long-term inflammatory responses that may contribute to cellular mutations and cancer cell proliferation.^(9–11) Patients with oral cancer have been shown to exhibit marked shifts in the salivary microbial profile compared with healthy individuals, suggesting a potential role for changes in the oral environment.^(12,13)

Such microbiological changes have also been reported in patients with cancer at distant sites. Increased levels of periodontal pathogens have been detected in the subgingival biofilms of patients with gastric malignancies.^(14,15) Additionally, Fusobacterium nucleatum, a well-recognized oral pathogen, has been detected in colorectal cancer cells and metastatic tumors,⁽¹⁶⁾ and elevated levels of this species have been correlated with gastric tumor size.⁽¹⁵⁾ Because the oral microbiome is one of the main sources contributing to the pulmonary microbiome, evidence suggests that oral microorganisms are associated with inflammatory processes and lung cancer pathogenesis.⁽¹⁷⁾ Although some studies have focused on the relationship with the whole oral microbiome,⁽⁷⁾ defined as the entire microbial community residing in a specific habitat such as the oral cavity,⁽⁶⁾ other evidence has highlighted the role of specific components of the oral microbiome, such as Fusobacterium spp. and P. gingivalis.^(11,16)

The relationship between cancer and the oral microbiome has therefore gained substantial scientific attention, as reflected in the rapid growth in related publications over the last decade. In this context, bibliometric studies can generate comprehensive data by systematically analyzing multiple indices, including citation counts for specific topics and broader scientific trends.^(18,19) Bibliometric studies have therefore been conducted across different fields to assess and characterize research activity within specific disciplines.^(20,21) Examining the most-cited papers in a field can provide valuable insights into influential publications, topic scope, and current research trends.^(18,19) However, no bibliometric analysis has specifically mapped the 100 most-cited papers on the relationship between cancer and the oral microbiome.

This study aimed to qualitatively and quantitatively analyze the 100 most-cited papers investigating the relationship between the oral microbiome and cancer.

From the 1,033 records retrieved, the 100 most-cited papers in the field were ranked and selected. The most-cited article had accumulated 759 citations in Scopus over a 6-year period, from its publication in 2019 to the search date in 2025, whereas the paper ranked 100th had received 52 citations (Table 1). All included articles were published between 1998 and 2022, with a publication peak in 2019, which accounted for 19 papers (Figure 1A). North America and Asia contributed the largest number of highly cited papers, with 38 and 37 publications, respectively; however, most papers did not involve international collaboration (Figure 1B). Regarding study design, reviews were the most prevalent (n=40), followed by cross-sectional observational studies (n=28) (Figure 1C). The United States of America was the country with the highest number of publications among the 100 most-cited papers (Figure 1D).

Oral, colorectal, esophageal, and pancreatic cancers were the most frequently investigated cancer sites among the highly cited papers (Figure 2A). Regarding microbial targets, most studies focused on the overall oral microbiome without restricting the analysis to specific species or genera (Figure 2B). Nevertheless, several bacterial species or genera were repeatedly examined, particularly Streptococcus spp., Porphyromonas gingivalis, and Fusobacterium nucleatum. When funding was evaluated according to study design, most case–control and in vitro studies reported financial support (Figure 2C). With respect to citation performance, papers with reported funding showed higher mean citation counts descriptively (Figure 2D). The two continents that contributed the largest number of highly cited papers, North America and Asia, also showed higher proportions of funded studies (Figure 2E). No clear pattern was observed between cancer site and funding status; however, most studies focusing on oral and colorectal cancers reported funding support (Figure 2F). Papers addressing colorectal, pancreatic, and oral cancers also tended to show higher citation counts (Figure 2G). Scientific Reports and Oral Oncology had the highest number of publications among the 100 most-cited papers on the relationship between cancer and the oral microbiome, with 6 and 5 papers, respectively (Table 2).

In the bivariate analysis evaluating associations between funding support and other study characteristics among the 100 most-cited papers, funding was less frequently reported in review papers than in case–control studies (OR=0.28; p=0.041) and in papers from Europe than in those from North America (OR=0.14; p<0.001). In contrast, the likelihood of funding support increased over the years (OR=1.05; p=0.037) (Table 3). No variable showed a statistically significant (p<0.05) relationship with international collaboration (Table 3). However, studies with international collaboration showed higher odds of being published in an open-access format, although this association did not reach statistical significance (p=0.098).

Oral microorganisms contribute to prevalent oral conditions and have been associated with the progression of various systemic diseases, including cancer.^(22–24) Although these organisms have not been shown to cause cancer, their presence has been associated with modulation of the host immune system, the release of bioactive metabolites, and inflammatory processes involved in tumor progression.⁽⁵⁾ Although some mechanisms and roles of oral microorganisms in cancer, particularly at sites distant from the oral cavity, remain unclear, mapping trends among the most-cited papers may help identify research patterns and underexplored areas in this field. Here, we identified the most-cited papers published up to 2025 that evaluated the relationship between cancer and the oral microbiome. The findings showed that most papers were published within the last seven years before the search date, including the most-cited paper, which was published in 2019. Most papers were reviews and were published mainly by authors from North America and Asia; funding support was less frequently reported when corresponding authors were from South America, Africa, or Oceania. Although most papers focused on the relationship between oral bacteria and oral cancer, a trend was also observed toward studies evaluating specific oral bacterial species and their roles in cancers at other human sites, such as colorectal, esophageal, and pancreatic cancers.

In vivo evidence has demonstrated marked changes in the salivary and local microbiota of patients with oral cancer, suggesting a potential role of the microbiome in inflammatory processes and immune responses.⁽²⁵⁾ Because oral microorganisms are closely associated with oral surfaces and oral biofilms have a well-recognized role in oral inflammatory diseases, the association between the oral microbiome and cancer has gained increasing attention, which may explain the growing number of published papers. The translocation of oral microorganisms to distant human sites is also well recognized, and these organisms have been associated with various systemic conditions, such as diabetes, Alzheimer's disease, and cardiovascular disease.^(26,27) Accordingly, researchers have increasingly evaluated the role of the oral microbiome in cancers at sites distant from the oral cavity. Among the most-cited papers, studies investigated the relationship between the oral microbiome and cancers of the esophagus, colorectum, pancreas, and other sites. Because this analysis focused on the most-cited papers, more recent studies not included in the top 100 may have explored these associations using newer experimental approaches and may provide further insights into the field.

High-throughput techniques have enabled researchers to gain a more detailed understanding of the oral microbiome and the microbial communities that colonize oral surfaces. Although most included studies focused on the effects of the overall oral microbiome on cancer, some examined specific bacterial species or genera, particularly abundant genera such as Streptococcus and well-recognized oral pathogens such as Porphyromonas gingivalis and Fusobacterium nucleatum. F. nucleatum has been detected in metastatic cells associated with colorectal cancer,⁽¹⁶⁾ and P. gingivalis has been implicated in inducing an inflammatory microenvironment in orodigestive carcinomas.⁽²⁸⁾ These findings suggest that research in this field has increasingly focused on specific microbial targets, rather than solely evaluating the potential role of the overall oral microbiome, to better characterize individual organisms, their mechanisms, and their effects. Thus, highly cited papers focusing on specific questions and microbial targets appear to have been well recognized in the field.

Although evidence regarding the role of oral microorganisms in cancer has received considerable attention over the last decade, most highly cited papers in this analysis were reviews. Meta-trend studies have shown that review articles are more likely to receive higher citation counts, with estimates indicating that reviews can be cited up to three times more often than original research articles.⁽²⁹⁾ However, nonsystematic narrative reviews are particularly prone to citation bias and may fail to adequately acknowledge the original sources of information.⁽³⁰⁾ Therefore, although review papers elucidating the role of oral microorganisms in cancer have been widely cited, further original research may be needed to generate new evidence in the field.

Funding is essential for advancing scientific knowledge and supporting health research. Although journals require the declaration of financial support, some do not provide standardized submission protocols, which may lead to biased reporting and underestimation of funding.⁽³¹⁾ Among the 100 most-cited papers, funding was more frequently reported in highly cited articles, studies focusing on oral cancer, case–control studies, and papers published by corresponding authors from North America. The bivariate analysis showed a significantly lower likelihood of funding being reported in Europe than in North America. Moreover, review papers were less likely to report funding. The profile identified may help authors and stakeholders understand funding patterns in this field and identify areas that may benefit from further support.

The limitations of the present study include the use of a single database, as other databases may contain different studies and citation counts, potentially influencing the findings. Therefore, including other databases may affect the ranking and profile presented. Although this approach has been used in previous bibliometric studies,^(18,21) incorporating additional databases may highlight different aspects of the topic. Moreover, focusing on the most-cited papers limits the inclusion of more recently published studies. However, highly cited papers are generally considered influential contributions in the field and may help researchers identify publication patterns in this area.

This bibliometric analysis shows that research on the relationship between cancer and the oral microbiome has expanded substantially over the past decade, with a strong emphasis on oral cancer and review-based publications. Highly cited papers predominantly originated from North America and Asia and focused on both the overall oral microbiome and specific bacterial taxa, whereas funding support increased over time but remained unevenly distributed across regions and study designs. These findings suggest that the mapped literature may have gaps regarding mechanistic and experimental studies on cancers at sites distant from the oral cavity and highlight the importance of sustained funding and international collaboration in supporting further research on the oral microbiome–cancer relationship.