The role of human papillomavirus in the pathogenesis of sinonasal inverted papilloma: a narrative review

Abstract

Sinonasal inverted papillomas (IPs) are rare tumours arising from the nasal epithelial mucosa. Most lesions are benign, but a subset of IPs progress to dysplasia and squamous cell carcinoma. Although the epidemiology and clinical features of IPs are well known, the pathogenesis is still unclear. Given the established role of human papillomaviruses (HPVs) in the formation of other mucosal tumours including cervical and oropharyngeal cancer, some have suggested the virus may play a role in IP development. However, the association between HPV and IPs has not yet been proven, and the variable detection of HPV DNA in IPs has cast uncertainty on whether the virus plays a major role in pathogenesis. In this review, we summarize early clinical reports and synthesize recent studies that may elucidate the association between HPV and IPs. We also discuss the role HPV may have in the progression of benign IP to dysplasia and malignancy, as well as potential pathological mechanisms. We hope that synthesizing the initial and recent studies on this topic will not only lead to a better understanding of research in the role of HPV in IP development, but also help guide and contextualize future studies. K E Y W O R D SHPV, inverted papilloma, review, sinonasal papilloma, virology | INTRODUCTIONInverted papilloma (IP) is a rare benign epithelial tumour of the sinonasal tract. 1 The annual incidence rate of IP is approximately 0.6 cases per 100,000 people, and it comprises between 0.5% and 4% of all primary nasal tumours. 2 Despite its overall rarity, IP is the most common form of sinonasal papilloma. 1 IPs tend to occur more commonly in males, with a ratio between two and five males to one female. 1 The mean age at presentation is roughly 55 years. 3 The diagnosis is usually made via nasal endoscopy showing a red-grey exophytic, polypoidal, and vascular lesion typically arising from the lateral nasal wall. 2 Despite being benign, IPs have a high rate of recurrence and are known for local aggressiveness. 4,5 Progression to synchronous or metachronous squamous cell carcinoma (SCC) is a hallmark of these lesions, with occurrence ranging from 2% to 27% of IPs. 6 The lesions are typically diagnosed by otolaryngologists and head and neck cancer specialists; however, patients with IPs may present to a variety of specialists. 2,7 IPs typically present with unilateral nasal obstruction, rhinorrhoea, epistaxis or sinusitis with nasal discharge. 2 While the epidemiology and clinical features of IP have been well characterized, the aetiology and risk factors remain controversial.Infection with human papillomavirus (HPV) is one such debated risk factor that has been posited to play a role in the pathogenesis of IP.Abbreviations: DIP, dysplastic inverted papilloma; EGFR, epidermal growth factor receptor; HPV, human papillomavirus; IP, inverted papilloma; ISH, in situ hybridization; MIP, malignant inverted papilloma; NMIP, non-malignant inverted papilloma; PCR, polymerase chain reaction; RT-PCR, reverse transcription polymerase chain reaction; SC...

HPV-Associated Benign Squamous Cell Papillomas in the Upper Aero-Digestive Tract and Their Malignant Potential

“…Some studies also stratified the analyses of SNIP by histology, separating non-malignant (NM-SNIPs) from those with dysplasia (D-SNIPs), as well as those with concurrent malignancy (M-SNIPs). In total, 20.9% (228/1092) NM-SNIPs, 52.6% ( n = 40/76) D-SNIPs, and 23.6% (29/123) M-SNIPs tested HPV-positive, thus disclosing the highest HPV prevalence (>50%) in SNIP with concomitant dysplasia [ 34 ].…”

Malignant Sinonasal Tumors: Update on Histological and Clinical Management

“…Additional non-occupational risk factors for TuNSs development include tobacco, nasal polyposis, inverted sinusal papilloma [ 16 , 17 ], chronic sinusitis and, finally, radiotherapy used for the treatment of retinoblastoma, a hereditary eye tumor that generally affects children. Evidence from literature suggests that also smoking tobacco can increase the risk of sinonasal tumors [ 15 , 18 , 19 ] and, in particular, of the squamous cell subtype (SNSCC) [ 19 , 20 , 21 ]. A report [ 19 ] showed a significant increase in the risk of developing TuNSs in patients exposed to wood dust with an odds ratio (OR) of 1.72 (CI 95%: 1.16–2.56) adjusted for many relevant risk factors, including tobacco smoking.…”

A rare case of cervical squamous cell carcinoma combined with sinonasal inverted Papilloma: A case report

“…According to the carcinogenicity, HPV is divided into high-risk types with carcinogenicity, and low-risk types without carcinogenicity. HPV 16,18,31,33,35,39,45,51,52,56,58 and 59 are the identi ed high-risk types. The continuous infection of these high-risk HPV is easy to lead to a variety of cancers, especially closely related to the occurrence of cervical cancer.…”