Abstract
Squamous cell papilloma (SCP) in the upper aero-digestive tract is a rare disease entity with bimodal age presentation both at childhood and in adults. It originates from stratified squamous and/or respiratory epithelium. Traditionally, SCPs have been linked to chemical or mechanical irritation but, since the 1980s, they have also been associated with human papillomavirus (HPV) infection. Approximately 30% of the head and neck SCPs are associated with HPV infection, with this association being highest for laryngeal papillomas (76–94%), followed by oral (27–48%), sinonasal (25–40%), and oropharyngeal papillomas (6–7%). There is, however, a wide variation in HPV prevalence, the highest being in esophageal SCPs (11–57%). HPV6 and HPV11 are the two main HPV genotypes present, but these are also high-risk HPVs as they are infrequently detected. Some 20% of the oral and oropharyngeal papillomas also contain cutaneous HPV genotypes. Despite their benign morphology, some SCPs tend to recur and even undergo malignant transformation. The highest malignant potential is associated with sinonasal inverted papillomas (7–11%). This review discusses the evidence regarding HPV etiology of benign SCPs in the upper aero-digestive tract and their HPV-related malignant transformation. In addition, studies on HPV exposure at an early age are discussed, as are the animal models shedding light on HPV transmission, viral latency, and its reactivation.
Highlights
The upper aero-digestive tract is composed of the nasal cavity, paranasal sinuses, nasopharynx, oral cavity, oropharynx, hypopharynx, larynx, trachea, and esophagus
As many cutaneous human papillomavirus (HPV) genotypes identified in normal nasal mucosa have been associated with skin carcinomas, there is an urgent need to study the role of β -and γ-HPV genera in Sinonasal Papilloma (SNP) and SNP-derived SCCs
We found in our Finnish Family HPV Study that HPV16 associated cellmediated immunity (CMI) was shifted towards cytokines IL-5 and IL-10 and IL-17A in children born with an HPV DNA-positive placenta and/or HPV-positive cord blood [69,70]
Summary
The upper aero-digestive tract is composed of the nasal cavity, paranasal sinuses, nasopharynx, oral cavity, oropharynx, hypopharynx, larynx, trachea, and esophagus. Squamous cell papillomas (SCPs) are histologically benign growths encountered practically at all body sites where squamous epithelium exists (e.g., skin, eye conjunctiva, paranasal sinuses, pharynx, oral cavity, larynx, esophagus, bronchus, genital tract, urinary tract) [1]. TThis rreevviieeww ssuummmmaarrizes tthhe kkeeyy ffeeaattuurreess ooff SSCCPPss iinntthheeuuppppeerraaeerroo--ddiiggeessttiivveettrraacctt ((FFiigguurree 11)),, iinncclluuddiinngg tthhee ttrraacchheeaa aanndd eessoopphhaagguuss. SNOPs are characterized by both inverted and exophytic growth pattern but differ from the other papilloma subtypes by their pseudostratified columnar epithelial lining, with cells containing abundant, granular eosinophilic cytoplasm and small, hyperchromatic nuclei. Another characteristic feature is the frequent presence of numerous intraepithelial micro-cysts. Recurrent lesions were more common among smokers than nonsmokers (75% vs. 31%), but none of the lesions presented with any degree of dysplasia [30]
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