International Journal of Head and Neck Surgery
Volume 14 | Issue 2 | Year 2023

A Case of Human Papillomavirus-positive Nasal Vestibule Squamous Cell Carcinoma

Mervyn Owusu-Ayim1, Somayyeh Shahsavari2, Jaiganesh Manickavasagam3

1,3School of Medicine, Imaging Science and Technology, University of Dundee, Dundee, United Kingdom; Department of Ear, Nose & Throat, Ninewells Hospital, Dundee, United Kingdom

2Department of Ear, Nose & Throat, Ninewells Hospital, Dundee, United Kingdom

Corresponding Author: Mervyn Owusu-Ayim, School of Medicine, Imaging Science and Technology, University of Dundee, Dundee, United Kingdom; Department of Ear, Nose & Throat, Ninewells Hospital, Dundee, United Kingdom, e-mail:

Received on: 29 July 2022; Accepted on: 22 December 2022; Published on: 08 June 2023


A 68-year-old man with a history of recurrent right epistaxis was diagnosed with a case of human papillomavirus (HPV)-positive nasal squamous cell carcinoma (SCC) on biopsy. A computed tomography (CT) scan revealed an infiltrative right nasal mass with surrounding bone destruction. The tumor was described to be invading the right nasal alar, medial rectus, and lacrimal punctum. Further involvement of the right maxillary nasal process was noted. Immunohistochemistry revealed a lesion with a surface epithelium exhibiting high-grade cytonuclear atypia and conferring positivity for p16 and HPV. After deliberation with the local head and neck multidisciplinary team (MDT), it was decided this case was not fit for surgical excision due to tumor involvement of the eye. The patient was offered a combination of radiotherapy with chemotherapy and responded well to treatment. HPV is prevalent in tumors of the sinonasal (SN) tract although, at present, limited information is available on the clinical profile of individuals diagnosed with this condition. We report a peculiar case of HPV-positive nasal SCC and evaluate the current understanding of the disease within the literature.

How to cite this article: Owusu-Ayim M, Shahsavari S, Manickavasagam J. A Case of Human Papillomavirus-positive Nasal Vestibule Squamous Cell Carcinoma. Int J Head Neck Surg 2023;14(2):36-39.

Source of support: Nil

Conflict of interest: None

Keywords: Head and neck cancer, Human papillomavirus, Squamous cell carcinoma.


Sinonasal (SN) malignancies are a rare group of disorders that account for <3% of head and neck cancers. Of these tumors, squamous cell carcinoma (SCC) is the most common type identified on histology.1 SN-SCC frequently arises from the maxillary sinus, with the nasal cavity being the next most common origin.2 Associated risk factors include welding fumes and arsenic, whereas exposure to wood and leather dust increases the risk of SN adenocarcinoma.3 Furthermore, smoking has been associated with the development of SN-SCC.4 At the initial stages, patients have nonspecific symptoms, such as nasal congestion, rhinorrhea, and headache. Thus, diagnosis usually occurs when the disease is at an advanced stage.5 Treatment is based on surgical extraction and high-dose radiotherapy, although delivery of this treatment regime can be problematic due to the close relation of lesions with the skull base and local vital organs.6

Globally, HPV counts as the most common sexually transmitted disease, with studies reporting that within the United Kingdom, 50–80% of sexually active men will contract the virus in their lifetime.7,8 The incidence of head and neck cancers due to HPV is increasing, as witnessed in the rising of oral cavity SSC rates within the last few decades.9 In recent times, the role of the virus in head and neck cancers has been explored, with studies establishing its prognostic properties in oropharyngeal SCC10 Despite this, the etiological role of the virus in SN-SCC has not yet been confirmed, although it is understood to play a part in the transformation of inverted papillomas to malignant carcinomas.11,12 Studies have demonstrated a positive association between human papillomavirus (HPV)-positive SN-SCC and overall survival, with research identifying a greater overall 5-year survival in those with the virus, compared to their negative counterparts.13-15 Here, we describe a case of HPV-positive nasal SCC and highlight its unusual presentation.


A 68-year-old male smoker, with no prior history of nasal injuries, presented to clinic reporting a 30-year history of recurrent right nose bleeds. This was initially controlled via cautery which took place on his right side around 28 years ago. However, his bleeding recurred after being placed on clopidogrel due to a transient ischemic attack in 2013. Further cautery on his right side settled his symptoms until his most recent presentation, where he reported continuous right nose bleeds. Associated symptoms, such as pain, nasal fullness, and rhinorrhea were not present. Members of his family also mentioned an alteration in his visual appearance, stating a change in his nasal structure. No other medical history was identified.

On examination, there was visible splaying of the right nasal bone. Endoscopy revealed cobblestoning of the right nasal mucosa whilst the left side appeared unremarkable (Fig. 1). Due to the unusual nature of the presentation, urgent biopsies, and imaging scans were taken to exclude malignancy.

Fig. 1: Images from endoscopic examination of the right nose showing bleeding and abnormal mucosa. (← shows lateral nasal wall, * displays nasal septum, and ! highlights nasal roof. There is visible bleeding and an abnormal mucosa in the right image)

A noncontrast CT scan of the paranasal sinuses was initially performed, this went on to reveal an infiltrative 4 × 2 cm right-sided nasal mass, with local bone destruction and midline soft tissue involvement (Fig. 2). Posteriorly, the mass was described as extending into the right lacrimal fossa, lacrimal punctum, and anterior portion of the right medial rectus. Anteriorly, the lesion extended onto the anterior region of the right nasal alar, with portions of the tumor infiltrating the anterior right side of the cartilaginous nasal septum. Further erosion of the right lacrimal and nasal bones, bony nasal septum, and nasal process of the right maxilla were noted (Fig. 3). Staging work was undertaken by magnetic resonance imaging (MRI) where no distant metastasis was identified.

Fig. 2: CT scan of the paranasal sinuses in sagittal and axial view. An infiltrative 4 × 2 cm right-sided nasal mass exhibiting local bone destruction and midline soft tissue involvement is highlighted in red

Fig. 3: CT scan in axial and sagittal views demonstrating erosion of the right lacrimal and nasal bones, bony nasal septum, and nasal process of the right maxilla

A biopsy of the lesion was performed by an ear, nose, and throat (ENT) surgeon under general anesthetic and sent to immunohistochemistry for analysis. The samples revealed a surface epithelium exhibiting high-grade cytonuclear atypia. Further occasional highly atypical cells were found detached from the surface epithelium. Immunohistochemistry revealed lesion positivity for p63, p16 (cytoplasmic and nuclear), and further positivity for HPV in situ hybridization (ISH). There were negative results for S100 and Epstein–Barr virus ISH, therefore, establishing a diagnosis of SCC in situ with concomitant HPV infection.

In this case, surgical intervention was contraindicated due to the involvement of the eye. After deliberation at the local head and neck MDT, it was decided to offer a combination of radiotherapy and chemotherapy. The patient received a course of intensity-modulated radiotherapy (IMRT) in addition to six cycles of IV cisplatin. He has fared well on treatment, with eye irritation being the only complaint of treatment. This has since been treated with Carbomer eye gel. No other side effects or complications were reported and he remains under monthly review at the ENT/oncology clinic.


Sinonasal Cancer

Cancers of the nasal cavity and paranasal sinuses remain rare with SCC being most frequently identified.16 These lesions present at an advanced stage and thus carry an overall poor prognosis.17 Patients report nonspecific symptoms such as nasal obstruction and discharge, which can mimic inflammatory sinus disease.18 SCC is reported to be more common in males, with the overall incidence of the disease declining throughout the past three decades as a result of reduced exposure to occupational hazards.19

Prior research has discovered a high risk of SN carcinoma in individuals exposed to hazards through their occupation. Occupations that expose individuals to wood or leather dust, nickel, or welding fumes have all been associated with an increased risk of SN cancer.3 Mirabelli et al.20 investigated the correlation between nasal carcinoma risk and occupational exposure to chlorophenol, commonly used as a wood preservative. They discovered that for each year of substantial exposure, individuals were at an increased risk of nasal cancer. In addition, Mastrangelo et al.21 conducted a meta-analysis of epidemiologic studies where they discovered that workers exposed to cotton dust were at an increased risk of SN cancer.

Treatment of SN cancers remains a debated issue due to the rarity of the condition. Consequently, achieving a consensus on universal treatment guidelines for the condition has been difficult.6 Preoperative CT and MRI scans are performed to ascertain tumor size, location, and involvement with adjacent structures. Invasion of neighboring tissues, such as the eyes, lacrimal glands, optic nerves, and chiasm is not assessed appropriately on CT, therefore MRI is utilized for accurate characterization of the lesion.22 Staging of these malignancies is commonly conducted using the tumor, nodes, and metastases staging system provided by the American Joint Committee on Cancer.23

Approaches to treatment have traditionally encompassed multimodalities compiling endoscopic surgical extraction accompanied by postoperative radiotherapy, in particular for individuals with locally advanced disease.24 Systemic therapy options include the use of neoadjuvant chemotherapy or concurrent administration of chemotherapy with radiotherapy.25 Certain studies have investigated the experimental strategy of intra-arterial chemotherapy during or after regional treatment, with conflicting results on outcomes being reported.26 In our case, our patient was offered a course of IMRT with adjunct chemotherapy. IMRT is an advanced form of conformal radiotherapy.27 It has been shown to produce a better target coverage of tumor sites and is said to decrease the cases of treatment-related toxicity in SN cancers.28,29


High-risk HPV types (16 and 18) have been well-accepted as significant etiological factors in head and neck cancers.30 HPV-associated SCC principally arise in the oropharynx, with 80% of cancer cases in this region being caused by the disease. Previous research has identified the presence of the virus in tumors of the SN tract, although dissimilar results have obscured its role as a causative agent in this region.31,32 It is reported that up to 25% of cancers arising in the SN tract contain transcriptionally active HPV.14

The rationale of HPV as an etiological factor in SN cancer stems from previous research which either discovered its involvement in the malignant transformation of benign papillomas or by detection of the virus in tumor biopsies.16 A meta-analysis by Syrjänen et al.31 found an approximate 30% overall incidence of HPV in SN carcinomas. Lawson et al.33 performed systematic research seeking to identify rates of HPV in papilloma-associated carcinomas. It was found that SCCs not associated with papillomas had a 20% occurrence of HPV deoxyribonucleic acid. In our case, our patient did not have a previous background of inverted papilloma. This corroborates what was previously reported by Alos et al.15 who found that most HPV SCCs arose de novo and had no prior relationship to inverted papillomas.

HPV head and neck cancers are described as possessing distinct histopathologic features. They are said to be nonkeratinizing, contain basal cell features, and show a greater expression for p16.30 The most common viral subtypes discovered in these tumors include HPV 16, 18, 35, and 45.34 Recently, a separate tumor type was identified which exhibited features of SCC enclosing a component with resemblance to adenoid cystic carcinoma.14 Further discovery of similar histopathologic features in other samples led to the name of HPV-positive multi-phenotypic SN carcinoma being attributed to this tumor type.35

Similar to HPV-positive oropharyngeal tumors, neoplasms of the SN tract with HPV positivity have demonstrated favorable outcomes compared to their negative counterparts. Alos et al.15 further reported that those in their patient cohort with HPV-positive SN-SCC had a significantly improved prognosis compared to those that were HPV-negative. Further to this, Chowdhury et al.13 also found that individuals in their study with HPV SN-SCC had a greater median survival over 42 months compared to their negative counterparts.

Overall, HPV positivity is apparent in a substantial number of SCC cases of the SN tract. These cases are reported to confer a favorable prognosis and further work is required to determine the impact of HPV positivity in this patient group. This case emphasizes the role the virus plays in tumors within this region and further prospective work is required to determine ways of improving treatment strategies for this cohort. Clinicians should continue to have a high suspicion index in cases with unusual presentations.


Written consent was obtained from the patient regarding the use of images from their CT scan and the reporting of this case.


Mervyn Owusu-Ayim


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