Abstract
Aim
The aim of the present study was to evaluate the prevalence of HPV infection in oral leukoplakia, specifying the HPV genotypes eventually involved. We also compared the micro-biopsy and brushing HPV detecting efficacy.
Materials and methods
Consecutive patients with a presumptive diagnosis of oral leukoplakia were enrolled. Demographical, behavioral data (smoking, alcohol) and lesion features were recorded. Each patient underwent a brushing procedure, performed with a cytobrush rubbed on the lesion, and then a biopsy was performed. The brushing and micro-biopsy specimens were both analyzed with the HPV 28 Anyplex II Seegene RT-PCR. The prevalence of HPV infection was calculated considering the two methods’ outcomes separately and then combining both. Cohen’s k coefficient was used to assess the agreement between the two methods.
Results
Sixty-five patients were enrolled with a mean age of 60 years. The HPV infection prevalence was 17%, decreasing to 5% considering the brushing outcomes alone. The most frequently detected genotypes were 6 (12%), 11 (3%), 42 (3%), and 16 (3%). No statistically significant correlation was found between HPV infection and the variables analyzed, except for smoking and the type of mucosa (p < 0.05). The strength of agreement between cytobrush and micro-biopsy was “fair” (k = 0.384).
Conclusions
The present study showed a low prevalence of HPV infection in oral leukoplakia. The micro-biopsy appeared to be more reliable than brushing in detecting HPV DNA in oral leukoplakia, but the method invasiveness discourages its employ as a screening tool. The importance of HPV in the etiopathogenesis of oral potentially malignant lesions remains unclear; further studies are needed to establish the HPV role in oral leukoplakia.
Clinical relevance
HPV involvement in oral leukoplakia and an effective and appropriate detecting technique are still a debated issue. From this study, the restricted use of brushing did not appear sufficient to assess the presence of HPV infection with PCR techniques in samples obtained from oral leukoplakia.
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References
Castellsagué X (2008) Natural history and epidemiology of HPV infection and cervical cancer. Gynecol Oncol 110(3):4–7
Kreimer AR, Villa A, Nytray AG et al (2011) The epidemiology of oral HPV infection among a sample of healthy men. Cancer Epidemiol Biomark Prev 1(20):172–182
Doorbar J (2005) The papilloma virus life cycle. J Clin Virol 32:7–15
World Health Organization International Agency for Research on Cancer (2007) IARC monographs on the evaluation of carcinogenic risks to humans – human papillomaviruses 90
Akagi K (2014) Genome-wide analysis of HPV integration in human cancers reveals recurrent, focal genomic instability. Genome Res 24(2):185–199
Kumaraswamy KL, Vidhya M (2011) Human papilloma virus and oral infections: an update. J Cancer Res Ther 7(2):120–127
Liu Z, Rashid T, Nytray AG (2015) Penises not required: a systematic review of the potential for human papillomavirus horizontal transmission that is non-sexual or does not include penile penetration. Sex Health 13(1):10–21
Raj AT, Patil S, Gupta AA, Rajkumar C, Awan KH (2018) Reviewing the role of human papillomavirus in oral cancer using the Bradford Hill criteria of causation. Dis Mon 18:30126–30123
Tam S, Fu S, Xu L, Krause KJ, Lairson DR, Miao H, Sturgis EM, Dahlstrom KR (2018) The epidemiology of oral human papillomavirus infection in healthy populations: a systematic review and meta-analysis. Oral Oncol 82:91–99
https://gco.iarc.fr. Accessed 15th January 2019
Mello FW, Miguel AFP, Dutra KL, Porporatti AL, Warnakulasuriya S, Guerra ENS, Rivero ERC (2018) Prevalence of oral potentially malignant disorders: a systematic review and meta-analysis. J Oral Pathol Med 47(7):633–640
Reibel J, Gale N, Hille J et al (2017) Oral potentially malignant disorders and oral epithelial dysplasia. In: El-Naggar AK, Chan JKC, Grandis JR, Takata T, Slootweg PPJ (eds) WHO classification of head and neck tumours, 4th edn. IARC, Lyon, France, pp 112–115
Masthan KMK, Avindha Babu N, Leena Sankari S, Priyadharsini C (2017) Leukoplakia: a short review on malignant potential. J Pharm Bioallied Sci 7:165–166
Speight PM, Khurram SA, Kujan O (2017) Oral potentially malignant disorders: risk of progression to malignancy. Oral Surg Oral Med Oral Pathol Oral Radiol 125(6):612–627
Syrjänen S, Lodi G, von Bûltzingslöwen I et al (2011) Human papillomaviruses in oral carcinoma and oral potentially malignant disorders: a systematic review. Oral Dis 17:58–72
Pierangeli A, Cannella F, Scagnolari C et al (2016) Frequent detection of high human papillomavirus DNA loads in oral potentially malignant disorders. Clin Microbiol Infect 1(22):95
Roberts CC, Liaw KL, Skjaldestad FE, Jansen KU, Bryan JT (2009) Importance of specimen type in detecting human papillomavirus DNA from the female genital tract. J Med Virol 81(9):1620–1626
Lawton G, Thomas S, Schonrock J, Monsour F, Frazer I (1992) Human papillomaviruses in normal oral mucosa: a comparison of methods for sample collection. J Oral Pathol Med 21:265–269
Marque AE, Fernander LP, Cantarutti AL et al (2013) Assessing oral brushing technique as a source to collect DNA and its use in detecting human papillomavirus. Pathol Res Pract 5(209):291–229
Hettmann A, Demcsák A, Bach Á, Decsi G, Dencs Á, Pálinkó D, Rovó L, Terhes G, Urbán E, Buzás K, Nagy K, Takács M, Minarovits J (2018) Prevalence and genotypes of human papillomavirus in saliva and tumor samples of head and neck cancer patients in Hungary. Infect Genet Evol 59:99–106
Kumar R, Kumar Rai A, Das D et al (2015) Alcohol and tobacco increase risk of high-risk HPV infection in head and neck cancer patients: study from north-east region of India. PLoS One 10(10):e0140700
Salem A (2010) Dismissing links between HPV and aggressive tongue cancer in young patients. Ann Oncol 21(1):13–17
Prakash P, Khandare M, Kumar M et al (2013) Immunohistochemical detection of p16INK4a in leukoplakia and oral squamous cell carcinoma. J Clin Diagn Res 12(7):2793–2795
Sikka S, Sikka P (2014) Association of human papilloma virus 16 infection and p53 polymorphism among tobacco using oral leukoplakia patients: a clinicopathologic and genotypic study. Int J Prev Med 4(5):430–438
Campisi G, Giovannelli L, Aricò P et al (2004) HPV DNA in clinically different variants of oral leukoplakia and lichen planus. Oral Surg Oral Med Oral Pathol Pral Radiol Endod 6(98):705–711
Ostwald C, Rutsatz K, Schweder K, Schmidt W, Gundlach K, Barten M (2003) Human papillomavirus 6/11, 16 and 18 in oral carcinomas and benign oral lesions. Med Microbiol Immunol 3(192):145–148
Bhosale PG, Pandey M, Desai RS et al (2016) Low prevalence of transcriptionally active human papilloma virus in Indian patients with HNSCC and leukoplakia. Oral Surg Oral Med Oral Pathol Pral Radiol Endod 5(122):609–618
Mitra A, MacInture DA, Mahajan V et al (2017) Comparison of vaginal microbiota sampling techniques: cytobrush versus swab. Sci Rep 1(7):9802
Götz C, Bischof C, Wolff KD, Kolk A (2019) Detection of HPV infection in head and neck cancers: promise and pitfalls in the last years: a meta-analysis. Mol Clin Oncol 1(10):17–28
Syrjänen K, Syrjänen S (1989) Concept of the existence of human papillomavirus (HPV) DNA in histologically normal squamous epithelium of the genital tract should be re-evaluated. Acta Obstet Gynecol Scand 68(7):613–617
Termine N, Giovannelli L, Rodolico V, Matranga D, Pannone G, Campsi G (2012) Biopsy vs. brushing: comparison of two sampling methods in the detection of HPV-DNA in squamous cell carcinoma of the oral cavity. Oral Oncol 48(9):870–875
Gipson BJ, Robbins HA, Fakhry C, D’Souza G (2018) Sensitivity and specificity of oral HPV detection for HPV-positive head and neck cancer. Oral Oncol 77:52–56
Hesselink AT, Sahli R, Berkhof J, Snijders PJF, van der Salm ML, Agard D, Bleeker MCG, Heideman DAM (2016) Clinical validation of Anyplex TM II HPV HR detection according to the guidelines for HPV test requirements for cervical cancer screening. J Clin Virol 76:36–39
Baasland I, Romundstad PR, Eide ML, Jonassen CM (2019) Clinical performance of Anyplex II HPV28 by human papillomavirus type and viral load in a referral population. PLoS One (1)14
Prigge ES, Arbyn M, von Knebel DM, Reuschenbach M (2017) Diagnostic accuracy of p16 INK4a immunohistochemistry in oropharyngeal squamous cell carcinomas: a systematic review and meta-analysis. Int J Cancer 5(140):1186–1198
Nauta IH, Rietbergen MM, van Bokhoven AAJD et al (2018) Evaluation of the 8th TNM classification on p16-positive oropharyngeal squamous cell carcinomas in the Netherlands, and the importance of additional HPV DNA-testing. Ann Oncol 5(29):1273–1279
Fakhry C, Lacchetti C, Perez-Ordonez B (2019) Human papillomavirus testing in head and neck carcinomas: ASCO clinical practice guideline endorsement summary of the CAP guideline. J Oncol Pract 10(14):613–617
American Joint Committee on Cancer (2016) AJCC- Cancer staging manual, 8th edition
Pannone G, Rodolico V, Santoro A (2012) Evaluation of a combined triple method to detect causative HPV in oral and oropharyngeal squamous cell carcinomas: p16 immunohistochemistry, consensus PCR HPV-DNA, and in situ hybridization. Infect Agent Cancer 7:4
Dürst M, Dzarlieva-Petrusevska RT, Boukamp P, Fusenig NE, Gissmann L (2005) Molecular and cytogenetic analysis of immortalized human primary keratinocytes obtained after transfection with human papillomavirus type 16 DNA. Oncogene 1:251–256
Kreimer AR, Clifford GM, Boyle P, Franceschi S (2005) Human papillomavirus types in head and neck squamous cell carcinomas worldwide: a systematic review. Cancer Epidemiol Biomark Prev 14:467–475
Ha PK, Califano JA (2004) The role of human papillomavirus in oral carcinogenesis. Crit Rev Oral Biol Med 4(15):188–196
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Della Vella, F., Pannone, G., Patano, A. et al. Detection of HPV in oral leukoplakia by brushing and biopsy: prospective study in an Italian cohort. Clin Oral Invest 24, 1845–1851 (2020). https://doi.org/10.1007/s00784-019-03048-y
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DOI: https://doi.org/10.1007/s00784-019-03048-y