Abstract
Human papillomaviruses (HPVs) are causative of a group of clinically papillary lesions. The HPV-related lesions of the oral cavity include squamous papilloma, condyloma acuminatum, verruca vulgaris, and multifocal epithelial hyperplasia. Benign entities, such as verruciform xanthoma or giant cell fibroma, as well as malignancies, such as papillary squamous cell carcinoma and verrucous carcinoma, may be considered in the clinical and/or histologic differential diagnoses of these lesions. Mechanisms of infection, epidemiology, clinical presentations, histologic features, and differential diagnoses of the HPV-related oral pathologies are discussed. Current concepts of viral transmission, especially as pertaining to lesions in pediatric patients, and the impacts of HPV vaccination are reviewed.
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References
Graham SV. The human papillomavirus replication cycle, and its links to cancer progression: a comprehensive review. Clin Sci (Lond). 2017;131(17):2201–21.
Egawa N, Egawa K, Griffin H, Doorbar J. Human papillomaviruses; epithelial tropisms, and the development of neoplasia. Viruses. 2015;7(7):3863–90.
Doorbar J, Egawa N, Griffin H, Kranjec C, Murakami I. Human papillomavirus molecular biology and disease association. Rev Med Virol. 2015;25(Suppl 1):2–23.
Tam S, Fu S, Xu L, et al. The epidemiology of oral human papillomavirus infection in healthy populations: a systematic review and meta-analysis. Oral Oncol. 2018;82:91–9.
Sabeena S, Bhat P, Kamath V, Arunkumar G. Possible non-sexual modes of transmission of human papilloma virus. J Obstet Gynaecol Res. 2017;43(3):429–35.
Summersgill KF, Smith EM, Levy BT, Allen JM, Haugen TH, Turek LP. Human papillomavirus in the oral cavities of children and adolescents. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2001;91(1):62–9.
D’Souza G, Agrawal Y, Halpern J, Bodison S, Gillison ML. Oral sexual behaviors associated with prevalent oral human papillomavirus infection. J Infect Dis. 2009;199(9):1263–9.
Stanley MA. Epithelial cell responses to infection with human papillomavirus. Clin Microbiol Rev. 2012;25(2):215–22.
Bordignon V, Di Domenico EG, Trento E, et al. How human papillomavirus replication and immune evasion strategies take advantage of the host DNA damage repair machinery. Viruses. 2017;9(12).
Westrich JA, Warren CJ, Pyeon D. Evasion of host immune defenses by human papillomavirus. Virus Res. 2017;231:21–33.
Grabowska AK, Riemer AB. The invisible enemy—how human papillomaviruses avoid recognition and clearance by the host immune system. Open Virol J. 2012;6:249–56.
Lingen MW, Xiao W, Schmitt A, Jiang B, et al. Low etiologic fraction for high-risk human papillomavirus in oral cavity squamous cell carcinomas. Oral Oncol. 2013;49(1):1–8.
Abbey LM, Page DG, Sawyer DR. The clinical and histopathologic features of a series of 464 oral squamous cell papillomas. Oral Surg Oral Med Oral Pathol. 1980;49(5):419–28.
Eversole LR. Papillary lesions of the oral cavity: relationship to human papillomaviruses. J Calif Dent Assoc. 2000;28(12):922–7.
Syrjänen S. Human papillomavirus infections and oral tumors. Med Microbiol Immunol. 2003;192(3):123–8.
Mammas IN, Sourvinos G, Spandidos DA. Human papilloma virus (HPV) infection in children and adolescents. Eur J Pediatr. 2009;168(3):267–73.
Plasencia JM. Cutaneous warts: diagnosis and treatment. Prim Care. 2000;27(2):423–34.
Pringle GA. The role of human papillomavirus in oral disease. Dent Clin N Am. 2014;58(2):385–99.
Eversole LR, Laipis PJ, Green TL. Human papillomavirus type 2 DNA in oral and labial verruca vulgaris. J Cutan Pathol. 1987;14(6):319–25.
Fatahzadeh M. Oral manifestations of viral infections. Atlas Oral Maxillofac Surg Clin N Am. 2017;25(2):163–70.
Tamiolakis P, Theofilou VI, Tosios KI, Sklavounou-Andrikopoulou A. Oral verruciform xanthoma: report of 13 new cases and review of the literature. Med Oral Patol Oral Cir Bucal. 2018;23(4):e429–35.
Eversole LR, Laipis PJ, Merrell P, Choi E. Demonstration of human papillomavirus DNA in oral condyloma acuminatum. J Oral Pathol. 1987;16(5):266–72.
Wenig BM. Squamous cell carcinoma of the upper aerodigestive tract: dysplasia and select variants. Mod Pathol. 2017;30(s1):112–8.
Esmeili T, Lozada-Nur F, Epstein J. Common benign oral soft tissue masses. Dent Clin N Am. 2005;49(1):223–40.
Sato M, Tanaka N, Sato T, Amagasa T. Oral and maxillofacial tumours in children: a review. Br J Oral Maxillofac Surg. 1997;35(2):92–5.
Knapp MJ. Oral disease in 181,338 consecutive oral examinations. J Am Dent Assoc. 1971;83(6):1288–93.
Frigerio M, Martinelli-Kläy CP, Lombardi T. Clinical, histopathological and immunohistochemical study of oral squamous papillomas. Acta Odontol Scand. 2015;73(7):508–15.
Bao Z, Yang X, Shi L, Feng J, Liu W, Zhou Z. Clinicopathologic features of oral squamous papilloma and papillary squamous cell carcinoma: a study of 197 patients from eastern China. Ann Diagn Pathol. 2012;16(6):454–8.
Carneiro TE, Marinho SA, Verli FD, Mesquita AT, Lima NL, Miranda JL. Oral squamous papilloma: clinical, histologic and immunohistochemical analyses. J Oral Sci. 2009;51(3):367–72.
Houston GD. The giant cell fibroma. A review of 464 cases. Oral Surg Oral Med Oral Pathol. 1982;53(6):582–7.
Fitzpatrick SG, Neuman AN, Cohen DM, Bhattacharyya I. Papillary variant of squamous cell carcinoma arising on the gingiva: 61 cases reported from within a larger series of gingival squamous cell carcinoma. Head Neck Pathol. 2013;7(4):320–6.
Mehrad M, Carpenter DH, Chernock RD, et al. Papillary squamous cell carcinoma of the head and neck: clinicopathologic and molecular features with special reference to human papillomavirus. Am J Surg Pathol. 2013;37(9):1349–56.
Lacey CJ, Lowndes CM, Shah KV. Chapter 4: Burden and management of non-cancerous HPV-related conditions: HPV-6/11 disease. Vaccine. 2006;24(Suppl 3):3/35–41.
Panici PB, Scambia G, Perrone L, et al. Oral condyloma lesions in patients with extensive genital human papillomavirus infection. Am J Obstet Gynecol. 1992;167(2):451–8.
Zunt SL, Tomich CE. Oral condyloma acuminatum. J Dermatol Surg Oncol. 1989;15(6):591–4.
Kui LL, Xiu HZ, Ning LY. Condyloma acuminatum and human papilloma virus infection in the oral mucosa of children. Pediatr Dent. 2003;25(2):149–53.
Squires J, Persaud DI, Simon P, Sinn DP. Oral condylomata in children. Arch Pediatr Adolesc Med. 1999;153(6):651–4.
Carlos R, Sedano HO. Multifocal papilloma virus epithelial hyperplasia. Oral Surg Oral Med Oral Pathol. 1994;77(6):631–5.
Archard HO, Heck JW, Stanley HR. Focal epithelial hyperplasia: an unusual oral mucosal lesion found in Indian children. Oral Surg Oral Med Oral Pathol. 1965;20:201–12.
Said AK, Leao JC, Fedele S, Porter SR. Focal epithelial hyperplasia—an update. J Oral Pathol Med. 2013;42(6):435–42.
Bennett LK, Hinshaw M. Heck’s disease: diagnosis and susceptibility. Pediatr Dermatol. 2009;26(1):87–9.
García-Corona C, Vega-Memije E, Mosqueda-Taylor A, et al. Association of HLA-DR4 (DRB1*0404) with human papillomavirus infection in patients with focal epithelial hyperplasia. Arch Dermatol. 2004;140(10):1227–31.
Pilarski R, Burt R, Kohlman W, Pho L, Shannon KM, Swisher E. Cowden syndrome and the PTEN hamartoma tumor syndrome: systematic review and revised diagnostic criteria. J Natl Cancer Inst. 2013;105(21):1607–16.
Jett K, Friedman JM. Clinical and genetic aspects of neurofibromatosis 1. Genet Med. 2010;12(1):1–11.
Kahn MA, Cote GJ, Gagel RF. RET protooncogene mutational analysis in multiple endocrine neoplasia syndrome type 2B: case report and review of the literature. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1996;82(3):288–94.
Patton LL. Oral lesions associated with human immunodeficiency virus disease. Dent Clin N Am. 2013;57(4):673–98.
Curi DS, Leite-Ribeiro PM, Torregrossa VR, Vieira VC, Sarmento VA. Efficacy of imidazolquinoline on treatment of condyloma acuminatum of the buccal mucosa. Spec Care Dent. 2017;37(1):51–4.
Cheng L, Leibovich BC, Cheville JC, et al. Squamous papilloma of the urinary tract is unrelated to condyloma acuminata. Cancer. 2000;88(7):1679–86.
Sinclair KA, Woods CR, Sinal SH. Venereal warts in children. Pediatr Rev. 2011;32(3):115–21. quiz 121.
Jenny C, Crawford-Jakubiak JE, Neglect, CoCAa, Pediatrics AAo. The evaluation of children in the primary care setting when sexual abuse is suspected. Pediatrics. 2013;132(2):e558–67.
Blomberg M, Friis S, Munk C, Bautz A, Kjaer SK. Genital warts and risk of cancer: a Danish study of nearly 50 000 patients with genital warts. J Infect Dis. 2012;205(10):1544–53.
Garland SM, Kjaer SK, Muñoz N, et al. Impact and effectiveness of the quadrivalent human papillomavirus vaccine: a systematic review of 10 years of real-world experience. Clin Infect Dis. 2016;63(4):519–27.
Guo T, Eisele DW, Fakhry C. The potential impact of prophylactic human papillomavirus vaccination on oropharyngeal cancer. Cancer. 2016;122(15):2313–23.
Cyrus N, Blechman AB, Leboeuf M, et al. Effect of quadrivalent human papillomavirus vaccination on oral squamous cell papillomas. JAMA Dermatol. 2015;151(12):1359–63.
Health.gov. Healthy People 2020. 2010. https://www.healthypeople.gov/search2/?query=human+papillomavirus+vaccine&op=Go. Accessed 15 Oct 2018.
Perez S, Zimet GD, Tatar O, Stupiansky NW, Fisher WA, Rosberger Z. Human papillomavirus vaccines: successes and future challenges. Drugs. 2018;78(14):1385–96.
Food and Drug Administration. FDA approves expanded use of Gardasil 9 to include individuals 27 through 45 years old. USDoHaH. 2018. https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm622715.htm. Accessed 10 Oct 2018.
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Betz, S.J. HPV-Related Papillary Lesions of the Oral Mucosa: A Review. Head and Neck Pathol 13, 80–90 (2019). https://doi.org/10.1007/s12105-019-01003-7
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DOI: https://doi.org/10.1007/s12105-019-01003-7