Human Papillomavirus Detection in Crevicular Fluid and Risk Stratification in Refractory Periodontitis: A Multicenter Cross-Sectional Study

Authors

  • Martha Rebolledo-Cobos DDS, Specialist in Stomatology and Oral Surgery, Master in Genetics. Professor, Universidad Metropolitana, Barranquilla, Colombia. GIOUMEB Research Group. Author https://orcid.org/0000-0002-0488-2464
  • Alejandra Herrera-Herrera DDS, Specialist in Epidemiology, Master in Pharmacology. Professor, Universidad Metropolitana, Barranquilla, Colombia. GIOUMEB Research Group. Author https://orcid.org/0000-0001-5830-5868
  • Jaime Plazas Román DDS, Specialist in Pediatric Dentistry and Maxillary Orthopedics, Master in Bioinformatics. Professor, School of Dentistry, University of Cartagena, Colombia. GITOUC Research Group. Author https://orcid.org/0000-0002-5040-6899
  • Luisa Barriga Periñan DDS, Specialist in Applied Statistics, Master in Epidemiology. Professor, School of Dentistry, University of Cartagena, Colombia. GITOUC Research Group. Author https://orcid.org/0000-0002-5226-6850
  • Martha Carmona Lorduy DDS, Specialist in Stomatology, Master in Education. Professor, School of Dentistry, University of Cartagena, Colombia. GITOUC Research Group. Author https://orcid.org/0000-0003-3066-2219

DOI:

https://doi.org/10.15517/6wy7yk89

Keywords:

Periodontitis; Human papillomavirus; Polymerase chain reaction; Gingival crevicular fluid; Risk assessment; Oral health.

Abstract

Refractory periodontitis affects treatment success rates and may be associated with viral reservoirs in periodontal pockets. Human papillomavirus (HPV) causes direct cytopathic effects on periodontal tissues and may contribute to treatment failure. This study aimed to detect HPV in crevicular fluid and develop a risk stratification tool for patients with refractory periodontitis. A cross-sectional multicenter study was conducted involving 80 patients with refractory periodontitis from two Colombian universities. HPV detection was performed using conventional and real-time duplex PCR in crevicular fluid samples. Sociodemographic and clinical variables were analyzed. Multivariate logistic regression and ROC curve analysis were used to develop and validate a risk prediction score. HPV prevalence was 15% (12/80 patients), with high-risk genotypes identified in 4 cases (33% of HPV-positive). Multivariate analysis revealed oral sex practice as the strongest independent predictor (OR=18.9; 95%CI: 4.2-85.3, p<0.001), followed by female sex (OR=2.8; 95%CI: 0.6-13.1) and age >50 years (OR=4.2; 95%CI: 0.5-35.7). The developed risk score showed excellent discriminative capacity (AUC-ROC=0.85; 95%CI: 0.74-0.96) with 75% sensitivity and 82% specificity at optimal cutoff. HPV detection in crevicular fluid using our validated risk stratification tool may identify patients with refractory periodontitis requiring modified therapeutic approaches. The risk score provides a practical clinical tool for HPV screening in periodontal practice.

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References

Papapanou P.N., Sanz M., Buduneli N., Dietrich T., Feres M., Fine D.H., et al. Periodontitis: Consensus report of workgroup 2 of the 2017 World Workshop on the Classification of Periodontal and Peri-Implant Diseases and Conditions. J Clin Periodontol. 2018; 45: S162-70.

Forman D., de Martel C., Lacey C.J., Soerjomataram I., Lortet-Tieulent J., Bruni L., et al. Global burden of human papillomavirus and related diseases. Vaccine. 2012; 30: F12-23.

Chaturvedi A.K., Anderson W.F., Lortet-Tieulent J., Curado M.P., Ferlay J., Franceschi S., et al. Worldwide trends in incidence rates for oral cavity and oropharyngeal cancers. J Clin Oncol. 2013; 31: 4550-9.

Hormia M., Willberg J., Ruokonen H., Syrjänen S. Marginal periodontium as a potential reservoir of human papillomavirus in oral mucosa. J Periodontol. 2005; 76: 358-63.

Dayakar M.M., Shipilova A., Gupta D. Periodontal pocket as a possible reservoir for high-risk human papillomavirus: a pilot study. J Indian Soc Periodontol. 2016; 20: 136-40.

Cameron J.E., Mercante D., O'Brien M., Gaffga A.M., Leigh J.E., Fidel P.L. Jr., et al. The impact of highly active antiretroviral therapy and immunodeficiency on human papillomavirus infection of the oral cavity of human immunodeficiency virus-seropositive adults. Sex Transm Dis. 2005; 32: 703-9.

Parra B., Slots J. Detection of human viruses in periodontal pockets using polymerase chain reaction. Oral Microbiol Immunol. 1996; 11: 289-93.

Escalona L., Veitía D., Perrone M. Detección de Virus Papiloma Humano en el fluido gingival de pacientes con inmunodeficiencia humana y enfermedad periodontal. Invest Clín. 2011; 52: 207-15.

Sritippho T., Chotjumlong P., Lamaroon A. Roles of Human Papillomaviruses and p16 in Oral Cancer. Asian Pac J Cancer Prev. 2015; 16: 6193-200.

Botero J., Bedoya E. Determinants of periodontal diagnosis. Rev Clin Periodoncia Implantol Rehabili Oral. 2010; 3: 94-9.

Şahiner F., Kubar A., Yapar M., Şener K., Dede M., Gümral R. Detection of major HPVs by a new multiplex real-time PCR assay using type-specific primers. J Microbiol Methods. 2014; 97: 44-50.

Tsakogiannis D., Papacharalampous M., Toska E., Kyriakopoulou Z., Dimitriou T.G., Ruether I.G., et al. Duplex Real-time PCR assay and SYBR green I melting curve analysis for molecular identification of HPV genotypes 16, 18, 31, 35, 51 and 66. Mol Cell Probes. 2015; 29: 13-8.

Albandar J.M., Susin C., Hughes F.J. Manifestations of systemic diseases and conditions that affect the periodontal attachment apparatus: Case definitions and diagnostic considerations. J Clin Periodontol. 2018; 45: 171-89.

Chapple I., Mealey B., Van Dyke T. Consensus report: Periodontal health and gingival diseases/conditions. J Clin Periodontol. 2018; 45: 68-77.

Chow S.C., Shao J., Wang H. Sample Size Calculations in Clinical Research. 2nd ed. New York: Marcel Dekker; 2008.

Rojas G., Silva S. Técnica sencilla para determinar la presencia de genotipos virales y bacterianos en pacientes con enfermedad periodontal. Rev Cient Odontol. 2011; 7: 75-9.

de Roda Husman A.M., Walboomers J.M., van den Brule A.J., Meijer C.J., Snijders P.J. The use of general primers GP5 and GP6 elongated at their 3' ends with adjacent highly conserved sequences improves human papillomavirus detection by PCR. J Gen Virol. 1995; 76: 1057-62.

Gravitt P.E., Peyton C.L., Alessi T.Q., Wheeler C.M., Coutlée F., Hildesheim A., et al. Improved amplification of genital human papillomaviruses. J Clin Microbiol. 2000; 38: 357-61.

Breiman L. Random forests. Machine Learn. 2001; 45: 5-32.

Friedman J.H. Greedy function approximation: a gradient boosting machine. Ann Stat. 2001; 29: 1189-232.

Robin X., Turck N., Hainard A., Tiberti N., Lisacek F., Sanchez J.C., et al. pROC: an open-source package for R and S+ to analyze and compare ROC curves. BMC Bioinformatics. 2011; 12: 77.

DeLong E.R., DeLong D.M., Clarke-Pearson D.L. Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. Biometrics. 1988; 44: 837-45.

Harrell F.E. Jr. Regression Modeling Strategies: With Applications to Linear Models, Logistic Regression, and Survival Analysis. 2nd ed. New York: Springer; 2015.

Viechtbauer W. Conducting meta-analyses in R with the metafor package. J Stat Softw. 2010; 36: 1-48.

Rouder J.N., Speckman P.L,. Sun D., Morey R.D., Iverson G. Bayesian t tests for accepting and rejecting the null hypothesis. Psychon Bull Rev. 2009; 16: 225-37.

Steyerberg E.W., Harrell F.E. Jr., Borsboom G.J., Eijkemans M.J., Vergouwe Y., Habbema JD. Internal validation of predictive models: efficiency of some procedures for logistic regression analysis. J Clin Epidemiol. 2001; 54: 774-81.

Collins G.S., Reitsma J.B., Altman D.G., Moons K.G. Transparent reporting of a multivariable prediction model for individual prognosis or diagnosis (TRIPOD): the TRIPOD statement. BMJ. 2015; 350: g7594.

Pencina M.J., D'Agostino R.B. Sr., D'Agostino R.B. Jr., Vasan R.S. Evaluating the added predictive ability of a new marker: from area under the ROC curve to reclassification and beyond. Stat Med. 2008; 27: 157-72.

Van Calster B., Wynants L., Verbeek J.F., Verbakel J.Y., Christodoulou E., Vickers A.J., et al. Reporting and interpreting decision curve analysis: a guide for investigators. Eur Urol. 2018; 74: 796-804.

Riley R.D., Ensor J., Snell K.I., Harrell F.E. Jr., Martin G.P., Reitsma J.B., et al. Calculating the sample size required for developing a clinical prediction model. BMJ. 2020; 368: m441.

Published

2026-02-25