EGFR mutation and HPV infection in sinonasal inverted papilloma and squamous cell carcinoma

Cabal, Virginia N.; Menéndez, Maité Hernández; Vivanco, Blanca; Potes-Ares, Sira; Riobello, Cristina; Suárez-Fernández, Laura; García-Marín, Rocío; Blanco-Lorenzo, Verónica; López, Fernando Gómez; Álvarez-Marcos, César; Llorente, José Luis Sáez; Hermsen, Mario

doi:10.4193/rhin19.371

Cited by 26 publications

(45 citation statements)

References 26 publications

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“…Human papillomavirus (HPV), indeed, plays a role in SNSCCs. Analyzed as part of a previously published study by our group, 10% (5/50) of our cases were found positive [39], similar to other SNSCC studies [40][41][42]. These HPV-positive cases may be thought to escape immune surveillance.…”

Section: Discussionsupporting

confidence: 85%

Prognostic and Therapeutic Implications of Immune Classification by CD8+ Tumor-Infiltrating Lymphocytes and PD-L1 Expression in Sinonasal Squamous Cell Carcinoma

García-Marín

Reda

Riobello

et al. 2021

IJMS

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Sinonasal squamous cell carcinoma (SNSCC) is an aggressive tumor predominantly arising in the maxillary sinus and nasal cavities. Advances in imaging, surgical and radiotherapeutic techniques have reduced complications and morbidity; however, the prognosis generally remains poor, with an overall 5-year survival rate of 30–50%. As immunotherapy may be a new therapeutic option, we analyzed CD8+ tumor-infiltrating lymphocytes (TILs) and the tumor microenvironment immune type (TMIT, combining CD8+ TILs and PD-L1) in a series of 57 SNSCCs. Using immunohistochemistry, tissue samples of 57 SNSCCs were analyzed for expression of CD8 on TILs and of PD-L1 on tumor cells. The results were correlated to the clinical and survival data. In total, 88% (50/57) of the tumors had intratumoral CD8+ TILs; 19% (11/57)—CD8high (>10%); and 39/57 (68%)—CD8low (1–10%). PD-L1 positivity (>5%) was observed in 46% (26/57) of the SNSCCs and significantly co-occurred with CD8+ TILs (p = 0.000). Using univariate analysis, high intratumoral CD8+ TILs and TMIT I (CD8high/PD-L1pos) correlated with a worse survival rate. These results indicate that SNSCCs are immunogenic tumors, similar to head and neck squamous cell carcinomas. Nineteen percent of the cases were both CD8high and PD-L1pos and this subgroup may benefit from therapy with immune checkpoint inhibitors.

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Section: Discussionsupporting

confidence: 85%

Prognostic and Therapeutic Implications of Immune Classification by CD8+ Tumor-Infiltrating Lymphocytes and PD-L1 Expression in Sinonasal Squamous Cell Carcinoma

García-Marín

Reda

Riobello

et al. 2021

IJMS

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“…In the literature, EGFR mutations have been hitherto demonstrated in 38 to 88% of ISPs [ 3 , 16 ] and in 50 to 88% of ISP-associated SSCCs [ 10 , 16 ]: Cabal et al found EGFR exon 20 mutations in 38% (7/18) of ISPs and in 50% (6/12) of ISP-associated SSCCs, while EGFR exon 20 mutations in ISP-unassociated SSCC occurred in only 5.3% (1/19) [ 16 ]. Sasaki et al reported EGFR mutation in 100% (9/9) of ISPs and 83% (10/12) of ISPs associated with SSCC, the vast majority being exon 20 insertions.…”

Section: Discussionmentioning

confidence: 99%

EGFR and BRAF mutations in inverted sinonasal papilloma — a more complex landscape?

2020

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Inverted (Schneiderian) sinonasal papilloma (ISP) is a neoplasm derived from mucosa of the sinonasal tract characterized by local aggressive growth, a tendency to recur and an association with sinonasal carcinoma. The etiology of ISP remains unclear. Recently, identical mutations in exons 19 and 20 of the oncogene EGFR were reported in ISP and ISP-associated sinonasal carcinoma. Nevertheless, it remains unclear whether recurring ISPs show identical EGFR mutations at different time points or whether these mutations are identical throughout the respective ISP sample. We used Sanger sequencing to test 60 formalin-fixed paraffin embedded ISP samples from 40 patients regarding mutations in exons 19 and 20 of EGFR—together with exon 15 of BRAF. Overall, 32 samples of 22 patients showed a mutation in EGFR exon 20, whereas 28 samples of 18 patients showed none. No mutation in EGFR exon 19 was found in any sample. Four samples of four patients showed a BRAF exon 15 mutation. Interestingly, samples of four patients exhibited genetic heterogeneity, enabling us to report this in ISP for the first time.

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“…Other studies have also found similar rates. Udager et al found an HPV‐positivity rate of 27.8% among SNSCCs, while Cabal et al found a rate of 20% 13,14 . A 2013 systemic review and meta‐analysis by Syrjänen and Syrjänen examining 492 SNSCCs across 35 studies found an HPV‐positivity rate of 27%, 15 while the previously mentioned study by Oliver et al found an HPV‐positivity rate of 31.5% 10 .…”

Section: Discussionmentioning

confidence: 95%

The prognostic significance of human papilloma virus in sinonasal squamous cell carcinoma

Markovic

Marqueen

Sindhu

et al. 2020

Laryngoscope Investig Oto

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Background: Human papilloma virus (HPV) has been implicated in the pathology of oropharyngeal head and neck cancers, but its role in sinonasal squamous cell carcinoma (SNSCC) has not been well established. Methods: Thirty-two patients with SNSCC diagnosed between 2011 and 2018 were identified and stratified by HPV status and viral serotype, as determined by PCR. Endpoints including recurrence, metastases and survival were analyzed using the Kaplan-Meier method. Results: Seventeen (53%) patients were HPV-positive and 15 (47%) were HPV-negative. The median follow-up time of living patients was 30.7 months (range 4-123 months). Survival did not differ by HPV status, but HPV+ tumors were more likely to locally recur and metastasize. When stratifying by treatment type, the lowest rate of recurrence occurred in patients receiving surgery and chemoradiation. Conclusion: A significant proportion of sinonasal tumors appear to be associated with HPV. Testing for HPV might be justified in all cases of sinonasal cancers. Further investigation is warranted to better understand the role of HPV in SNSCC. K E Y W O R D S human papilloma virus (HPV), prognosis, sinonasal carcinoma 1 | INTRODUCTION Sinonasal carcinomas are rare malignancies, comprising about 3% of head and neck cancers with an incidence of less than 1 per 100 000 in the United States. 1 Although the incidence has been declining in recent years, clinical outcomes remain poor. 2 While there is significant histologic heterogeneity among these tumors, the most common histology is sinonasal squamous cell carcinoma (SNSCC), which accounts for 60% to 75% of sinonasal carcinomas. 2 The pathogenesis of SNSCC is not yet clearly understood, but several environmental exposures, such as wood dust and certain chemicals, have been identified as risk factors. The association, however, is stronger for sinonasal adenocarcinoma. 3 Furthermore, unlike squamous cell carcinomas arising in other sites of the head Results of this manuscript were presented at the 2020 Multidisciplinary Head and Neck Conference (Feb. 27-29, Scottsdale, AZ).

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EGFR mutation and HPV infection in sinonasal inverted papilloma and squamous cell carcinoma

Cited by 26 publications

References 26 publications

Prognostic and Therapeutic Implications of Immune Classification by CD8+ Tumor-Infiltrating Lymphocytes and PD-L1 Expression in Sinonasal Squamous Cell Carcinoma

Prognostic and Therapeutic Implications of Immune Classification by CD8+ Tumor-Infiltrating Lymphocytes and PD-L1 Expression in Sinonasal Squamous Cell Carcinoma

EGFR and BRAF mutations in inverted sinonasal papilloma — a more complex landscape?

The prognostic significance of human papilloma virus in sinonasal squamous cell carcinoma

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