Relationship between the prevalence of oral human papillomavirus DNA and periodontal disease (Review)

  • Authors:
    • Hideo Shigeishi
    • Masaru Sugiyama
    • Kouji Ohta
  • View Affiliations

  • Published online on: February 26, 2021     https://doi.org/10.3892/br.2021.1416
  • Article Number: 40
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Human papillomavirus (HPV) is a small DNA virus that infects the basal keratinocytes of squamous epithelium in the skin, and in the oral and genital mucosa. Smoking and sexual behavior have been recognized as significant risk factors for oral HPV infection. In the present review, the findings of recent studies of oral HPV infection in relation to periodontitis are discussed, as well as periodontopathic bacteria and periodontal herpes virus. Previous research suggests that HPV localizes to the inflammatory periodontal tissue. Inflammatory periodontal pockets may thus act as a reservoir for HPV. The interactions between HPV and periodontopathic bacteria remain unclear, but it is hypothesized that oral HPV infection may be related to a characteristic oral microbiome. Smoking is associated with HPV and periodontitis, as smoking induces destruction of periodontal tissue and suppresses the host defense, allowing HPV to infect periodontal tissue. Carcinogenic HPV and periodontitis may lead to the development of oral cavity cancer. However, oral HPV E6/E7 expression (transcriptionally active HPV) has not yet been fully investigated in patients with periodontitis. Collectively, the evidence suggests that oral HPV prevalence may be associated with periodontitis. The effect of clinical factors (age, sex, smoking, immunosuppressive condition and vaccination) on oral HPV DNA prevalence should be considered when clarifying the relationship between oral HPV and periodontitis. Additionally, the sampling method should be carefully chosen to directly detect HPV DNA in periodontal tissues.

1. Introduction

Human papillomavirus (HPV) is a small DNA virus that infects the basal keratinocytes of the squamous epithelium through micro-wounds and abrasions in the skin and mucosa (1). To date, >150 HPV genotypes have been identified, of which ~40 infect the mucosa (mucosal HPV types) (1). Mucosal HPV types that infect the anogenital mucosa have also been shown to also infect the mucosa of the oral cavity (2). Smoking and sexual behavior have been recognized as predominant risk factors for oral HPV infection (3).

Several studies have been performed to investigate the association between HPV prevalence and periodontal disease (4-15). Periodontal diseases such as gingivitis and periodontitis are polymicrobial infectious diseases that affect epithelial tissue (the gingiva), tooth-supporting connective tissue (the periodontal ligament) and alveolar bone. Periodontal disease is a major cause of tooth loss, and is caused by interactions between periodontopathic bacteria, host immune responses and environmental factors (for example, smoking) (16). Periodontopathic bacteria such as Treponema denticola, Tannerella forsythia and Porphyromonas gingivalis serve vital roles in the pathogenesis of periodontal disease (17). Importantly, periodontal disease causes destruction of the crevicular epithelium (16), which may increase the opportunity for HPV to infect basal cells in the epithelium.

Oral virome analyses have revealed that several human viruses are stable members of the microbiota, and oral viruses display a sex-specific prevalence (18). Previous research has demonstrated that, together with periodontal disease-related bacteria, the herpes virus serves a significant role in the pathogenesis of periodontal disease (19). However, it remains to be elucidated whether oral HPV is implicated in periodontitis and the virulence of periodontopathic bacteria. In the present review, the findings of recent studies of oral HPV prevalence in relation to periodontitis are discussed, as well as periodontopathic bacteria and periodontal herpes virus.

2. Association between oral HPV and periodontitis

The PubMed search engine was used to search papers using the following key words: ‘(HPV OR human papillomavirus) AND (periodontitis OR periodontal disease)’, yielding 118 papers published between June 1980 and October 2020. After reviewing the titles and abstracts for relevance, reviews and meta-analyses (n=25), case reports (n=23), in vitro or animal studies (n=8), articles that focused on cancer and pre-malignant lesions (n=20), hyperplastic lesions (n=2), periapical lesions (n=5) or odontogenic cysts (n=1), as well as other articles, including news (n=3), editorials and commentaries (n=3), letters to editors (n=1), congress (n=1), questionnaire surveys (n=1) or a demand study (n=1), were all excluded (Fig. 1). Additionally, clinical research papers with no data regarding the association between oral HPV infection and periodontitis (n=7), clinical research papers investigating HPV E6/E7 mRNA rather than HPV DNA (n=2), and articles not written in English (n=3) were excluded. This resulted in 12 original papers that investigated the association between oral HPV DNA prevalence and periodontal disease (4-15). Table I presents a summary of the studies included in the present literature review. Of the 12 papers that reported the association between oral HPV DNA and periodontal disease, periodontal tissue samples were used in 5 studies (4,6,7,9,11), oral swab samples were used in one study (8), oral rinse samples were used in 5 studies (10,12-15) and crevicular fluid samples were used in one study (5). A nucleic acid amplification assay (for example, PCR) was the most common detection method for HPV DNA and was employed in 11 of the 12 studies (5-15). Nucleic acid hybridization assays (such as southern blotting) were used for detection of HPV DNA (4,6).

Table I

Summary of studies included in the present literature review.

Table I

Summary of studies included in the present literature review.

Author, yearCountrySubjectsSampleDetection methodHPV DNA positive rate, % (positive n/total n)Refs.
Madinier et al, 1992France6 patients with adult periodontitis and 2 patients with rapidly progressive periodontitisGingival tissuesSouthern blotPercentages of HPV positivity were 16.7% (1/6) in patients with adult periodontitis and 50% (1/2) in patients with rapidly progressive periodontitis(4)
Parra and Slots, 1996USA30 patients with advanced periodontitisCrevicular fluid samplesPCR16.7% (5/30)(5)
Hormia et al, 2005Finland38 individuals with clinically diagnosed periodontal diseaseGingival tissuesPCR, southern blot25.8% (8/31)(6)
Horewicz et al, 2010Brazil56 systemically healthy adults with chronic periodontitisParaffin blocks of gingival tissuesPCR for HPV16 DNA detection0% (0/56)(7)
Fuster-Rossello et al, 2014Argentina11 women with HPV- associated gynecological diseases and periodontitisOral swab samplesPCRUnknown(8)
Jacob et al, 2014India67 systemically healthy participants with periodontitisGingival tissuesPCR for HPV16 DNA detection0% (0/67)(9)
Wiener et al, 2015USAParticipants with periodontal disease from the National Health and Nutrition Examination Survey data from between 2009 and 2012Oral rinse samplesPCR10.5% (309/2945)(10)
Baez et al, 2016Brazil74 kidney transplanted or non-transplanted patients with gingivitis and/or periodontitisGingivitis and/or periodontitis tissuesPCR41.9% (31/74)(11)
Sun et al, 2017Australia89 participants with periodontitisOral rinse samplesPCR for HPV16 DNA detection3.4% (3/89)(12)
Ortiz et al, 2018Puerto RicoParticipants of the San Juan Overweight Adults Longitudinal Study between 2014 and 2016Oral rinse samplesPCRPercentages of HPV positivity were 5.3% in patients with mild/moderate periodontitis and 11.3% in patients with severe periodontitis(13)
Ortiz et al, 2018Puerto RicoParticipants of the San Juan Overweight Adults Longitudinal Study between 2011 and 2013Oral rinse samplesPCRPercentages of HPV positivity were 4.4% (13/297) in patients with none/mild periodontitis, 4.1% (12/290) in those with moderate periodontitis, and 11.5% (17/148) in those with severe periodontitis(14)
McDaniel et al, 2020USAParticipants of the National Health and Nutrition Examination Surveys from between 2011 and 2012 as well as 2013 and 2014Oral rinse samplesPCRNot determined(15)

[i] HPV, human papillomavirus.

To assess the prevalence of oral HPV DNA using periodontal tissue samples, HPV DNA was detected in adult periodontitis and rapidly progressive periodontitis using gingival papilla specimens and southern blotting (4). Carcinogenic HPV DNA was detected in 26% of the gingival tissues obtained from patients with periodontitis by PCR (6). Furthermore, HPV DNA was visualized in the nucleus of the junctional epithelium using in situ hybridization (6). These results indicate that local periodontal inflammation may provide an opportunity for HPV to infect epithelial basal cells. Additionally, a higher HPV DNA positive rate was found in gingivitis and/or periodontitis biopsy samples from kidney transplant patients compared with those from non-transplanted patients (11). Conversely, Horewicz et al (7) reported that HPV16 DNA was not detected by PCR in any paraffin embedded-gingival tissues (chronic periodontitis, gingivitis or healthy periodontium) of Brazilian patients with good general health. Furthermore, HPV16 DNA was not detected by PCR in the marginal periodontium of systemically healthy patients, excluding pregnant women, patients with uncontrolled systemic diseases and smokers (9). It is speculated that the prevalence of HPV DNA is low in normal periodontal tissues. Patients with general good health maintain an effective local immune system which may provide a defense against HPV, and may explain the absence of HPV in periodontal tissues.

Oral swab samples from the external gingival epithelium and the internal gingival epithelium (the periodontal pocket epithelium) were used to detect HPV DNA by PCR in women with HPV-associated gynecological diseases, and 13.3% of external gingival epithelium samples and 16.7% of internal gingival epithelium were HPV DNA positive (8). However, there was no positive correlation between HPV DNA and the incidence and severity of periodontitis (8). The relationship between oral HPV DNA and oral health status (for example, plaque accumulation and bleeding in the gingival sulcus) was investigated using oral swab samples in individuals with no history of HPV vaccination (20). The detection rate for high risk type HPV was greater in the individuals with a high gingival bleeding index compared with those with a low index (20). A significant independent association was found between oral HPV DNA detection and plaque accumulation or gingival sulcus bleeding after adjustment for age and sex (20). Bleeding of the ulcerated epithelial surface of the periodontal pocket is considered a significant indicator of periodontal inflammation caused by periodontal pathogens (21). Thus, it is likely that oral HPV infection is significantly associated with periodontal inflammation.

Oral rinse samples were employed in 5 previous studies to investigate oral HPV prevalence (10,12-15). HPV DNA detection and genotyping were performed using oral rinse samples in 740 Hispanic adults (13). The prevalence of oral HPV DNA was significantly higher amongst individuals with severe periodontitis (11.3%) than those with mild or moderate periodontitis (5.3%) or no periodontitis (2.6%) (13). The same group also reported a significant association between oral HPV infection and the severity of periodontitis in Hispanic participants of the San Juan Overweight Adults Longitudinal Study between 2011 and 2013(14). Sun et al (12) investigated the relationship between oral HPV16 DNA and periodontal health status (including presence of bleeding on probing, dental calculus and periodontal pockets) by PCR, using oral rinse samples in patients at a dental school clinic. The HPV16 DNA detection rate was higher in individuals without periodontal disease (5.3%) than in those with periodontal disease (3.4%); however, no significant association was found between the oral HPV16 DNA detection rate and periodontal health status (12). Wiener et al (10) performed a study based on the National Health and Nutrition Examination Survey data and revealed that 58.7% of HPV positive participants had periodontitis, whereas 38.7% of HPV negative participants had periodontitis (10). A significant association was found between the presence of oral HPV DNA and periodontitis (10). However, no independent association was found between oral HPV DNA and periodontitis after adjustment for clinical factors such as sex, ethnicity, education, age, income to poverty ratio, smoking, alcohol use and number of lifetime sexual partners (10). Additionally, McDaniel et al (15) performed a study based on the National Health and Nutrition Examination Survey data between 2011 and 2012 as well as 2013 and 2014, and reported that the median predicted oral HPV prevalence rates were higher in individuals with periodontitis than in those without periodontitis amongst non-HPV-vaccinated individuals (15).

Gingival crevicular fluid contains not only serum and blood cells, but also periodontal epithelial cells and subgingival plaque (22). Therefore, gingival crevicular fluid can be used to investigate the localization of HPV in periodontal pockets. Parra and Slots (5) investigated the prevalence of HPV DNA by PCR using gingival crevicular fluid in patients with advanced periodontitis or gingivitis. HPV DNA was detected in 16.7% of patients with advanced periodontitis, but was not detected in patients with gingivitis (5). In our previous study, the presence of HPV16 DNA in gingival crevicular fluid collected by inserting paper points into periodontal pockets was investigated in middle-aged and older Japanese individuals (23). Of the 89 participants, four women (4.5%) were HPV16 DNA-positive, but no men exhibited HPV16 DNA positivity (23). Postmenopausal women were more likely to be infected with HPV in the cervix because of sex-hormone-related immunosuppression (24). Female sex hormones, such as progesterone, enhances the regulatory response to HPV16 virus-like particles in peripheral blood mononuclear cells (25). Therefore, postmenopausal women may be more susceptible to oral HPV infection as well as cervical HPV infection. It is thus considered that factors specific to women, such as reduced levels of sex hormones, may increase the risk of HPV infection in periodontal pockets.

The oral HPV detection rate may be affected by differences in sample detection methods. Oral rinse samples contain a mix of saliva, bacteria, epithelial cells and blood cells derived from various sites in the oral cavity. Furthermore, contamination of the pharynx by gargling may have affected the positive rate of HPV DNA in oral rinse samples because tonsillar tissue acts as a reservoir for microorganisms due to its specific anatomical and histological structure (26). It is thus considered that sampling methods, such as gingival tissue biopsies and crevicular fluid samples may be more appropriate to determine the presence of periodontal disease-related HPV.

Collectively, the evidence suggests that oral HPV infection may be associated with periodontitis. A recent systematic review and meta-analysis revealed a positive relationship between oral HPV infection and periodontitis, although the certainty of the evidence is low (27). It is important to consider the effect of clinical factors contributing to oral HPV infection (age, sex, smoking, immunosuppressive condition and vaccination) on HPV DNA prevalence to clarify the presence of periodontitis-related HPV. Additionally, sampling methods should be carefully chosen to directly detect HPV DNA in periodontal tissues. Further studies are required to demonstrate the presence of HPV in periodontal tissues and clarify the biological role of HPV in periodontitis.

3. Association between oral HPV and periodontopathic bacteria

Our previous study revealed that increased HPV16 E6 viral copy numbers were associated with an increased number of oral bacteria in hospital patients, which suggests that poor oral hygiene may be related to oral HPV infection and viral replication (28). Additionally, the HPV16 DNA positivity of gingival crevicular fluid was significantly associated with the prevalence of Treponema denticola and Fusobacterium nucleatum (23). It is thus considered that oral HPV prevalence is related to the presence of periodontal bacteria. Analysis of the microbiome shows a strong association between the diversity of the vaginal microbiota and HPV infection (29). Vaginal HPV infection and its persistent infection are characterized by a reduced abundance of vaginal Lactobacillus spp. (29). A significant relationship between carcinogenic HPV infection and the Prevotella genus was found in the vagina of HIV-negative participants (30). These observations suggest that changes in the microbiome may potentially facilitate vaginal HPV infection. The composition of the oral microbiome has been shown to reflect differences in the periodontal health condition (31). Prevotella- and Veillonella-dominant oral microbiomes were associated with the active phase of periodontitis amongst Japanese individuals (31). Conversely, Neisseria-, Haemophilus-, Aggregatibacter- and Porphyromonas-abundant oral microbiomes reflected healthy periodontal tissue (31). The relationship between the oral microbiome and oral HPV infection has not been fully elucidated, limited by the small number of studies and small sample sizes in these studies (32,33). The association between the composition of the bacterial microbiota and HPV DNA in the oral cavity was investigated in 39 Finnish women (32). Unclassified Bifidobacteriaceae and Finegoldia genera were significantly dominant, but the Haemophilus genus was less numerous in HPV positive cases than in HPV negative cases (32). Capnocytophaga ochracea was more abundant in HPV16 DNA positive periodontal granulation tissue than in HPV negative tissues in Indians (33). It has been reported that the oral viral community is significantly characterized according to the sex of the host (34), which indicates that human sex hormones may affect the composition of oral viromes. Furthermore, it is hypothesized that aging may be a significant factor affecting the composition of oral viromes as a result of declining immune function. Therefore, it is necessary to consider the effect of sex and age when evaluating the association between oral HPV and periodontopathic bacteria. Further analysis of microbial communities may provide greater insight into the relationship between HPV and specific oral bacteria.

4. Association between herpes virus and periodontitis

It is clear that the herpes virus is notably associated with periodontitis. Herpes viruses such as herpes simplex virus (HSV), human cytomegalovirus (HCMV) and Epstein-Barr virus (EBV) were detected with a wide range of positive percentages in gingivitis and chronic periodontitis (35-39). In two previous independent meta-analyses, it was suggested that oral EBV and HCMV are significantly associated with periodontitis (35,37). According to a review by Slots (38), the median prevalence of HSV, HCMV and EBV was 45, 40 and 32% in chronic periodontitis and 12, 3 and 7% in healthy periodontal tissue, respectively (38). Co-infection of herpes virus and periodontal disease-related bacteria induces the risk of periodontitis (40,41). Herpes virus-induced local proinflammatory cytokines in the presence of immunosuppression may contribute to periodontitis (38). Proinflammatory cytokines released by HCMV-infected gingival fibroblasts serve an important role in attracting cytotoxic T-cells and natural killer cells (41). Attachment of Actinobacillus actinomycetemcomitans to periodontal epithelial cells can be enhanced by HCMV (42). These results highlight the important role of herpes virus in periodontitis.

5. Association between oral HPV and herpes virus

Concurrent infection of the herpes virus and HPV was found in individuals with advanced periodontitis (5). The prevalence of both HPV DNA and EBV DNA in gingivitis and periodontitis tissue biopsies was 25% in kidney transplant patients, but 0% in non-transplanted patients (11). Kidney transplant patients receiving immunosuppressive therapy exhibited high HPV and EBV DNA positivity, which indicates that immunosuppressive conditions may elicit susceptibility to concurrent viral infection in the periodontium.

Several in vitro studies have been performed to investigate the biological relationship between HPV and the herpes virus (43-45). HSV facilitated integration and amplification of the HPV genome in HPV18 DNA-transfected cervical cancer cells (43). Co-expression of EBV latent membrane protein-1 and HPV16 E6 induced malignant transformation in primary mouse embryonic fibroblasts through NF-κB signaling (44). HPV can increase EBV genome stability and lytic reactivation of EBV in oral keratinocytes (45), which indicates that HPV promotes the pathogenicity of oral EBV. Collectively, these results suggest that HPV and the herpes virus induce adverse oncogenic events.

6. Association of smoking with oral HPV infection and periodontitis

Smoking causes the destruction of periodontal tissue through microcirculatory dysfunction and impairment of host immune systems (46). Therefore, smoking is a significant risk factor for periodontal disease (47). Notably, smoking is thought to cause dysbiosis of the periodontal microbiome (48), which suggests that the smoking-induced imbalance in the microbiome is detrimental to periodontal health. Several studies have demonstrated that smoking is a major risk factor for oral HPV infection (49-54). Our previous meta-analysis showed the association between oral HPV infection and smoking (3). Current smoking was a significant risk factor for oral HPV infection (3). Furthermore, smoking increased the duration of high-risk HPV infection in the oral cavity (55). These results suggest that smoking is a major risk factor for both oral HPV infection and periodontitis. It is thus speculated that HPV tends to infect the smoking-deteriorated periodontal tissue due to the suppression of the host defense by smoking.

Chronic inflammation in periodontitis contributes to the development of several types of cancer caused by carcinogens, such as ROS, produced by activated inflammatory cells in response to periodontal pathogens (56-59). Periodontopathic bacteria are reported to be a risk factor for oral squamous cell carcinomas (60,61). Furthermore, a history of periodontitis is importantly associated with the HPV status of patients with oral cavity cancer (62,63). Therefore, it is hypothesized that periodontitis can increase the possibility of adverse oncogenic events independently or cooperatively with oncogenic HPV.

HPV and smoking are thought to interact in carcinogenesis in the following manner. Smoking upregulates the number of HPV genome copies and promotes integration of viral genomes into the host genome in HPV-infected cells (64). Next, the HPV oncoproteins E6 and E7 inhibit p53 function, which results in accumulation of chromosomal instability and loss of cell cycle control (64). Finally, HPV-induced immortalization and tobacco smoke-associated DNA damage cause carcinogenesis (64). Therefore, persistent carcinogenic HPV infections induced through smoking may contribute to the development of HPV-related oral cavity cancer.

7. Conclusion

HPV localizes to inflammatory periodontal tissue and is thought to infect basal keratinocytes in the ulcerated gingival sulcus epithelium. Inflammatory periodontal pockets serve a significant role as a reservoir for HPV. Although the interactions between HPV and periodontopathic bacteria remain unclear, oral HPV infection may be associated with a characteristic oral microbiome. Smoking induces destruction of periodontal tissue, and HPV then tends to infect periodontal tissue due to the smoking-induced suppression of the host defense. Carcinogenic HPV and periodontitis are likely to contribute to the development of oral cavity cancers. However, to date, oral HPV E6/E7 expression (transcriptionally active HPV) has not been fully investigated in individuals with periodontitis. Collectively, the available literature suggests that oral HPV may be associated with periodontitis. To clarify the association between oral HPV and periodontitis, the effects of clinical factors contributing to oral HPV DNA prevalence should be considered. Additionally, methods of sampling that can directly detect HPV DNA in inflammatory periodontal tissues should be further investigated.

Acknowledgements

Not applicable.

Availability of data and materials

Not applicable.

Authors' contributions

HS contributed to the conception of the study and wrote the manuscript. MS and KO aided in writing the manuscript. All authors read and approved the final manuscript.

Ethics approval and consent to participate

Not applicable.

Patient consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

References

1 

zur Hausen H: Papillomaviruses and cancer: From basic studies to clinical application. Nat Rev Cancer. 2:342–350. 2002.PubMed/NCBI View Article : Google Scholar

2 

Kay P, Meehan K and Williamson AL: The use of nested polymerase chain reaction and restriction fragment length polymorphism for the detection and typing of mucosal human papillomaviruses in samples containing low copy numbers of viral DNA. J Virol Methods. 105:159–170. 2002.PubMed/NCBI View Article : Google Scholar

3 

Shigeishi H and Sugiyama M: Risk factors for oral human papillomavirus infection in healthy individuals: A systematic review and meta-analysis. J Clin Med Res. 8:721–729. 2016.PubMed/NCBI View Article : Google Scholar

4 

Madinier I, Doglio A, Cagnon L, Lefèbvre JC and Monteil RA: Southern blot detection of human papillomaviruses (HPVs) DNA sequences in gingival tissues. J Periodontol. 63:667–673. 1992.PubMed/NCBI View Article : Google Scholar

5 

Parra B and Slots J: Detection of human viruses in periodontal pockets using polymerase chain reaction. Oral Microbiol Immunol. 11:289–293. 1996.PubMed/NCBI View Article : Google Scholar

6 

Hormia M, Willberg J, Ruokonen H and Syrjänen S: Marginal periodontium as a potential reservoir of human papillomavirus in oral mucosa. J Periodontol. 76:358–363. 2005.PubMed/NCBI View Article : Google Scholar

7 

Horewicz VV, Feres M, Rapp GE, Yasuda V and Cury PR: Human papillomavirus-16 prevalence in gingival tissue and its association with periodontal destruction: A case-control study. J Periodontol. 81:562–568. 2010.PubMed/NCBI View Article : Google Scholar

8 

Fuster-Rossello L, Ribotta E, Cuffini C and Fuster-Juan M: Human papilloma virus in oral mucosa and its association with periodontal status of gynecologically infected women. Acta Odontol Latinoam. 27:82–88. 2014.PubMed/NCBI View Article : Google Scholar

9 

Jacob A, Janam P and Babu Vijayamma JM: Prevalence of human papilloma virus in marginal periodontium and its association with periodontitis: A cross sectional study. J Indian Soc Periodontol. 18:447–450. 2014.PubMed/NCBI View Article : Google Scholar

10 

Wiener RC, Sambamoorthi U and Jurevic RJ: Association of periodontitis and human papillomavirus in oral rinse specimens: Results from the National Health and Nutrition Survey 2009-2012. J Am Dent Assoc. 146:382–389. 2015.PubMed/NCBI View Article : Google Scholar

11 

Baez CF, Savassi-Ribas F, Rocha WM, Almeida SG, Gonçalves MT, Guimarães MA, Cavalcanti SM and Varella RB: Association of Epstein-Barr virus (EBV) but not human papillomavirus (HPV) with gingivitis and/or periodontitis in transplanted individuals. Rev Inst Med Trop São Paulo. 58(58)2016.PubMed/NCBI View Article : Google Scholar

12 

Sun CX, Bennett N, Tran P, Tang KD, Lim Y, Frazer I, Samaranayake L and Punyadeera C: A pilot study into the association between oral health status and human papillomavirus-16 infection. Diagnostics (Basel). 7(E11)2017.PubMed/NCBI View Article : Google Scholar

13 

Ortiz AP, González D, Vivaldi-Oliver J, Castañeda M, Rivera V, Díaz E, Centeno H, Muñoz C, Palefsky J, Joshipura K, et al: Periodontitis and oral human papillomavirus infection among Hispanic adults. Papillomavirus Res. 5:128–133. 2018.PubMed/NCBI View Article : Google Scholar

14 

Ortiz AP, González D, Ramos J, Muñoz C, Reyes JC and Pérez CM: Association of marijuana use with oral HPV infection and periodontitis among Hispanic adults: Implications for oral cancer prevention. J Periodontol. 89:540–548. 2018.PubMed/NCBI View Article : Google Scholar

15 

McDaniel JT, Davis JM, McDermott RJ, Maxfield I and Kapatamoyo K: Predicted prevalence of oral human papillomavirus (HPV) by periodontitis status and HPV vaccination status. J Public Health Dent. 80:132–139. 2020.PubMed/NCBI View Article : Google Scholar

16 

Kwon T, Lamster IB and Levin L: Current concepts in the management of periodontitis. Int Dent J: Dec 5, 2020 (Epub ahead of print). doi: 10.1111/idj.12630.

17 

Socransky SS, Haffajee AD, Cugini MA, Smith C and Kent RL Jr: Microbial complexes in subgingival plaque. J Clin Periodontol. 25:134–144. 1998.PubMed/NCBI View Article : Google Scholar

18 

Abeles SR, Robles-Sikisaka R, Ly M, Lum AG, Salzman J, Boehm TK and Pride DT: Human oral viruses are personal, persistent and gender-consistent. ISME J. 8:1753–1767. 2014.PubMed/NCBI View Article : Google Scholar

19 

Slots J: Human viruses in periodontitis. Periodontol 2000. 53:89–110. 2010.PubMed/NCBI View Article : Google Scholar

20 

Dalla Torre D, Burtscher D, Sölder E, Rasse M and Puelacher W: The correlation between the quality of oral hygiene and oral HPV infection in adults: A prospective cross-sectional study. Clin Oral Investig. 23:179–185. 2019.PubMed/NCBI View Article : Google Scholar

21 

Checchi L, Montevecchi M, Checchi V and Zappulla F: The relationship between bleeding on probing and subgingival deposits. An endoscopical evaluation. Open Dent J. 3:154–160. 2009.PubMed/NCBI View Article : Google Scholar

22 

Khurshid Z, Mali M, Naseem M, Najeeb S and Zafar MS: Human gingival crevicular fluids (GCF) proteomics: An overview. Dent J (Basel). 5(E12)2017.PubMed/NCBI View Article : Google Scholar

23 

Shigeishi H, Murodumi H, Ohta K and Sugiyama M: Detection of HPV16 E6 DNA in periodontal pockets of middle-aged and older people. Oral Sci Int. 18:50–55. 2021.

24 

Smith EM, Johnson SR, Ritchie JM, Feddersen D, Wang D, Turek LP and Haugen TH: Persistent HPV infection in postmenopausal age women. Int J Gynaecol Obstet. 87:131–137. 2004.PubMed/NCBI View Article : Google Scholar

25 

Marks MA, Gravitt PE, Burk RD, Studentsov Y, Farzadegan H and Klein SL: Progesterone and 17beta-estradiol enhance regulatory responses to human papillomavirus type 16 virus-like particles in peripheral blood mononuclear cells from healthy women. Clin Vaccine Immunol. 17:609–617. 2010.PubMed/NCBI View Article : Google Scholar

26 

Faraji F, Zaidi M, Fakhry C and Gaykalova DA: Molecular mechanisms of human papillomavirus-related carcinogenesis in head and neck cancer. Microbes Infect. 19:464–475. 2017.PubMed/NCBI View Article : Google Scholar

27 

Ali A, Lassi ZS, Kapellas K, Jamieson L and Rumbold AR: A systematic review and meta-analysis of the association between periodontitis and oral high-risk human papillomavirus infection. J Public Health (Oxf): Sep 11, 2020 (Epub ahead of print). doi: 10.1093/pubmed/fdaa156.

28 

Shigeishi H, Sugiyama M, Ohta K, Yokoyama S, Sakuma M, Murozumi H, Kato H and Takechi M: High HPV16 E6 viral load in the oral cavity is associated with an increased number of bacteria: A preliminary study. Biomed Rep. 8:59–64. 2018.PubMed/NCBI View Article : Google Scholar

29 

Mitra A, MacIntyre DA, Marchesi JR, Lee YS, Bennett PR and Kyrgiou M: The vaginal microbiota, human papillomavirus infection and cervical intraepithelial neoplasia: What do we know and where are we going next? Microbiome. 4(58)2016.PubMed/NCBI View Article : Google Scholar

30 

Dareng EO, Ma B, Famooto AO, Adebamowo SN, Offiong RA, Olaniyan O, Dakum PS, Wheeler CM, Fadrosh D, Yang H, et al: Prevalent high-risk HPV infection and vaginal microbiota in Nigerian women. Epidemiol Infect. 144:123–137. 2016.PubMed/NCBI View Article : Google Scholar

31 

Takeshita T, Nakano Y, Kumagai T, Yasui M, Kamio N, Shibata Y, Shiota S and Yamashita Y: The ecological proportion of indigenous bacterial populations in saliva is correlated with oral health status. ISME J. 3:65–78. 2009.PubMed/NCBI View Article : Google Scholar

32 

Tuominen H, Rautava S, Syrjänen S, Collado MC and Rautava J: HPV infection and bacterial microbiota in the placenta, uterine cervix and oral mucosa. Sci Rep. 8(9787)2018.PubMed/NCBI View Article : Google Scholar

33 

Chowdhry R, Singh N, Sahu DK, Tripathi RK, Mishra A, Singh A, Mukerjee I, Lal N, Bhatt MLB and Kant R: Dysbiosis and variation in predicted functions of the granulation tissue microbiome in HPV positive and negative severe chronic periodontitis. Biomed Res Int. 2019(8163591)2019.PubMed/NCBI View Article : Google Scholar

34 

Abeles SR and Pride DT: Molecular bases and role of viruses in the human microbiome. J Mol Biol. 426:3892–3906. 2014.PubMed/NCBI View Article : Google Scholar

35 

Gao Z, Lv J and Wang M: Epstein-Barr virus is associated with periodontal diseases: A meta-analysis based on 21 case-control studies. Medicine (Baltimore). 96(e5980)2017.PubMed/NCBI View Article : Google Scholar

36 

Rodrigues PM, Teixeira AL, Kustner EC and Medeiros R: Are herpes virus associated to aggressive periodontitis? A review of literature. J Oral Maxillofac Pathol. 19:348–355. 2015.PubMed/NCBI View Article : Google Scholar

37 

Botero JE, Rodríguez-Medina C, Jaramillo-Echeverry A and Contreras A: Association between human cytomegalovirus and periodontitis: A systematic review and meta-analysis. J Periodontal Res. 55:551–558. 2020.PubMed/NCBI View Article : Google Scholar

38 

Slots J: Periodontal herpesviruses: Prevalence, pathogenicity, systemic risk. Periodontol 2000. 69:28–45. 2015.PubMed/NCBI View Article : Google Scholar

39 

Zhu C, Li F, Wong MC, Feng XP, Lu HX and Xu W: Association between herpesviruses and chronic periodontitis: A meta-analysis based on case-control studies. PLoS One. 10(e0144319)2015.PubMed/NCBI View Article : Google Scholar

40 

Imbronito AV, Okuda OS, Maria de Freitas N, Moreira Lotufo RF and Nunes FD: Detection of herpesviruses and periodontal pathogens in subgingival plaque of patients with chronic periodontitis, generalized aggressive periodontitis, or gingivitis. J Periodontol. 79:2313–2321. 2008.PubMed/NCBI View Article : Google Scholar

41 

Botero JE, Parra B, Jaramillo A and Contreras A: Subgingival human cytomegalovirus correlates with increased clinical periodontal parameters and bacterial coinfection in periodontitis. J Periodontol. 78:2303–2310. 2007.PubMed/NCBI View Article : Google Scholar

42 

Teughels W, Sliepen I, Quirynen M, Haake SK, Van Eldere J, Fives-Taylor P and Van Ranst M: Human cytomegalovirus enhances A. actinomycetemcomitans adherence to cells. J Dent Res. 86:175–180. 2007.PubMed/NCBI View Article : Google Scholar

43 

Hara Y, Kimoto T, Okuno Y and Minekawa Y: Effect of herpes simplex virus on the DNA of human papillomavirus 18. J Med Virol. 53:4–12. 1997.PubMed/NCBI

44 

Shimabuku T, Tamanaha A, Kitamura B, Tanabe Y, Tawata N, Ikehara F, Arakaki K and Kinjo T: Dual expression of Epstein-Barr virus, latent membrane protein-1 and human papillomavirus-16 E6 transform primary mouse embryonic fibroblasts through NF-κB signaling. Int J Clin Exp Pathol. 7:1920–1934. 2014.PubMed/NCBI

45 

Makielski KR, Lee D, Lorenz LD, Nawandar DM, Chiu YF, Kenney SC and Lambert PF: Human papillomavirus promotes Epstein-Barr virus maintenance and lytic reactivation in immortalized oral keratinocytes. Virology. 495:52–62. 2016.PubMed/NCBI View Article : Google Scholar

46 

Ojima M and Hanioka T: Destructive effects of smoking on molecular and genetic factors of periodontal disease. Tob Induc Dis. 8(4)2010.PubMed/NCBI View Article : Google Scholar

47 

Mullally BH: The influence of tobacco smoking on the onset of periodontitis in young persons. Tob Induc Dis. 2:53–65. 2004.PubMed/NCBI View Article : Google Scholar

48 

Hanioka T, Morita M, Yamamoto T, Inagaki K, Wang PL, Ito H, Morozumi T, Takeshita T, Suzuki N, Shigeishi H, et al: Smoking and periodontal microorganisms. Jpn Dent Sci Rev. 55:88–94. 2019.PubMed/NCBI View Article : Google Scholar

49 

Antonsson A, Cornford M, Perry S, Davis M, Dunne MP and Whiteman DC: Prevalence and risk factors for oral HPV infection in young Australians. PLoS One. 9(e91761)2014.PubMed/NCBI View Article : Google Scholar

50 

Cook RL, Thompson EL, Kelso NE, Friary J, Hosford J, Barkley P, Dodd VJ, Abrahamsen M, Ajinkya S, Obesso PD, et al: Sexual behaviors and other risk factors for oral human papillomavirus infections in young women. Sex Transm Dis. 41:486–492. 2014.PubMed/NCBI View Article : Google Scholar

51 

Dahlstrom KR, Burchell AN, Ramanakumar AV, Rodrigues A, Tellier PP, Hanley J, Coutlée F and Franco EL: Sexual transmission of oral human papillomavirus infection among men. Cancer Epidemiol Biomarkers Prev. 23:2959–2964. 2014.PubMed/NCBI View Article : Google Scholar

52 

Hang D, Liu F, Liu M, He Z, Sun M, Liu Y, Li J, Pan Y, Ning T, Guo C, et al: Oral human papillomavirus infection and its risk factors among 5,410 healthy adults in China, 2009-2011. Cancer Epidemiol Biomarkers Prev. 23:2101–2110. 2014.PubMed/NCBI View Article : Google Scholar

53 

Lang Kuhs KA, Gonzalez P, Struijk L, Castro F, Hildesheim A, van Doorn LJ, Rodriguez AC, Schiffman M, Quint W, Lowy DR, et al: Costa Rica Vaccine Trial Group: Prevalence of and risk factors for oral human papillomavirus among young women in Costa Rica. J Infect Dis. 208:1643–1652. 2013.PubMed/NCBI View Article : Google Scholar

54 

Gillison ML, Broutian T, Pickard RK, Tong ZY, Xiao W, Kahle L, Graubard BI and Chaturvedi AK: Prevalence of oral HPV infection in the United States, 2009-2010. JAMA. 307:693–703. 2012.PubMed/NCBI View Article : Google Scholar

55 

Kero K, Rautava J, Syrjänen K, Willberg J, Grenman S and Syrjänen S: Smoking increases oral HPV persistence among men: 7-year follow-up study. Eur J Clin Microbiol Infect Dis. 33:123–133. 2014.PubMed/NCBI View Article : Google Scholar

56 

Michaud DS, Joshipura K, Giovannucci E and Fuchs CS: A prospective study of periodontal disease and pancreatic cancer in US male health professionals. J Natl Cancer Inst. 99:171–175. 2007.PubMed/NCBI View Article : Google Scholar

57 

Meyer MS, Joshipura K, Giovannucci E and Michaud DS: A review of the relationship between tooth loss, periodontal disease, and cancer. Cancer Causes Control. 19:895–907. 2008.PubMed/NCBI View Article : Google Scholar

58 

Chrysanthakopoulos NA: Periodontal disease - cancer association and the specific role of periodontal disease in lung cancer pathogenesis. Mathews J Dentistry. 3(018)2018.

59 

Hirschfeld J, White PC, Milward MR, Cooper PR and Chapple IL: Modulation of neutrophil extracellular trap and reactive oxygen species release by periodontal bacteria. Infect Immun. 85:e00297–e17. 2017.PubMed/NCBI View Article : Google Scholar

60 

Gholizadeh P, Eslami H, Yousefi M, Asgharzadeh M, Aghazadeh M and Kafil HS: Role of oral microbiome on oral cancers, a review. Biomed Pharmacother. 84:552–558. 2016.PubMed/NCBI View Article : Google Scholar

61 

Mager DL, Haffajee AD, Devlin PM, Norris CM, Posner MR and Goodson JM: The salivary microbiota as a diagnostic indicator of oral cancer: A descriptive, non-randomized study of cancer-free and oral squamous cell carcinoma subjects. J Transl Med. 3(27)2005.PubMed/NCBI View Article : Google Scholar

62 

Tezal M, Sullivan Nasca M, Stoler DL, Melendy T, Hyland A, Smaldino PJ, Rigual NR and Loree TR: Chronic periodontitis-human papillomavirus synergy in base of tongue cancers. Arch Otolaryngol Head Neck Surg. 135:391–396. 2009.PubMed/NCBI View Article : Google Scholar

63 

Tezal M, Scannapieco FA, Wactawski-Wende J, Hyland A, Marshall JR, Rigual NR and Stoler DL: Local inflammation and human papillomavirus status of head and neck cancers. Arch Otolaryngol Head Neck Surg. 138:669–675. 2012.PubMed/NCBI View Article : Google Scholar

64 

Wei L, Griego AM, Chu M and Ozbun MA: Tobacco exposure results in increased E6 and E7 oncogene expression, DNA damage and mutation rates in cells maintaining episomal human papillomavirus 16 genomes. Carcinogenesis. 35:2373–2381. 2014.PubMed/NCBI View Article : Google Scholar

Related Articles

Journal Cover

May-2021
Volume 14 Issue 5

Print ISSN: 2049-9434
Online ISSN:2049-9442

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Shigeishi H, Sugiyama M and Ohta K: Relationship between the prevalence of oral human papillomavirus DNA and periodontal disease (Review). Biomed Rep 14: 40, 2021
APA
Shigeishi, H., Sugiyama, M., & Ohta, K. (2021). Relationship between the prevalence of oral human papillomavirus DNA and periodontal disease (Review). Biomedical Reports, 14, 40. https://doi.org/10.3892/br.2021.1416
MLA
Shigeishi, H., Sugiyama, M., Ohta, K."Relationship between the prevalence of oral human papillomavirus DNA and periodontal disease (Review)". Biomedical Reports 14.5 (2021): 40.
Chicago
Shigeishi, H., Sugiyama, M., Ohta, K."Relationship between the prevalence of oral human papillomavirus DNA and periodontal disease (Review)". Biomedical Reports 14, no. 5 (2021): 40. https://doi.org/10.3892/br.2021.1416