Human papillomaviruses are identified in a subgroup of sinonasal squamous cell carcinomas with favorable outcome

Abstract

BACKGROUND:The role of human papillomavirus (HPV) in the pathogenesis of squamous cell carcinomas (SCCs) of the sinonasal tract and its clinicopathological implications were evaluated.METHODS:All SCCs of the sinonasal tract diagnosed in the Hospital Clinic of Barcelona from 1981 to 2006 were retrospectively evaluated (N = 60). Clinical and pathological data were reviewed. HPV infection was determined and typed by amplification of HPV DNA by polymerase chain reaction using the SPF‐10 primers. p16INK4a expression was determined by immunohistochemistry. Overall and progression‐free survival for HPV‐positive and ‐negative patients was estimated by Kaplan‐Meier analysis and by the use of a multivariate Cox proportional hazards model.RESULTS:HPV DNA was detected in tumor tissue of 12 of 60 (20%) patients. HPV16 was identified in 11 tumors and HPV35 in 1. Immunohistochemistry for p16INK4a stained all HPV‐positive and no HPV‐negative tumors (P < .001). No differences were observed in terms of site and histological grade or stage at presentation between HPV‐positive and ‐negative tumors. However, HPV‐positive patients had a significantly better 5‐year progression‐free survival (62%; 95% confidence interval [CI], 23%‐86% vs 20%; 95% CI, 9%‐34%; P = .0043, log‐rank test) and overall survival (80%; 95% CI, 20%‐96% vs 31%; 95% CI, 15%‐47%; P = .036, log‐rank test) than patients with HPV‐negative tumors. In multivariate analysis, HPV‐positive tumors were associated with improved progression‐free survival (hazard ratio, 0.21; 95% CI, 0.17‐0.98; P = .012).CONCLUSIONS:A subgroup of sinonasal SCCs is associated with HPV infection. These tumors have a significantly better prognosis. Cancer 2009. © 2009 American Cancer Society.

Sinonasal Squamous Cell Carcinoma: A Review with Emphasis on Emerging Histologic Subtypes and the Role of Human Papillomavirus

“…Due to these growth patterns, while the diagnosing pathologist could consider if NKSCC or papillary SCC represent malignant transformation of an inverted papilloma, both of these SCC types consist of diffuse, full thickness, overtly carcinomatous tumor, rather than being mixed with lower grade areas or with foci of actual inverted papilloma. Further, the SCCs that arise from inverted papillomas are almost always keratinizingtype SCC and not NK or papillary SCC [20].…”

“…Stoddard et al [28] recently studied inverted papillomas using RNA in situ hybridization for high risk HPV and found that all 19 papillomas were positive, but most at very low signal levels. Further, as it turns out, when closely examining the studies on transcriptionally-active high risk HPV in sinonasal SCC, the subset of 27 patients with inverted papilloma-related SCC had active HPV in only 2 cases (7.4 %) [7,20]. This suggests that the high risk HPV may be important for the growth of inverted papillomas and perhaps for carcinogenesis within them, but that it typically does not drive the growth of established tumors as it does in SCC of the oropharynx.…”

Human Papillomavirus in Non-Oropharyngeal Head and Neck Cancers: A Systematic Literature Review

“…SCC arising ex-inverted papillomas also reveal HPV RNA transcription, and evidence of viral integration [66]. [97]. There are limited data regarding sinonasal HPV ''carrier'' rates.…”

“…Good correlation between HPV? status, detected by either PCR or ISH, and diffuse p16 overexpression, has been reported in sinonasal SCC, albeit in small numbers [97,[119][120][121]. Strong diffuse p16 expression cannot be accepted as a surrogate HPV biomarker in any untested context, as this pattern of overexpression has also been detected in HPV-negative sinonasal undifferentiated carcinoma [122].…”

Comprehensive analysis of human papillomavirus prevalence and the potential role of low-risk types in verrucous carcinoma

“…[16][17][18] Infection with high-risk HPV has been associated with malignant transformation, and causally related to cervical cancer 19,20 and a subset of squamous cell carcinomas in the head and neck and anogenital region different from the cervix. [21][22][23] Verrucous carcinoma has been associated with both low-risk (types 6 and 11) and high-risk (types 16 and 18) types of HPV. 18,24,25 However, a causal relationship between HPV and verrucous carcinoma remains to be proven, specifically in those cases in which a low-risk HPV has been suggested to be involved in the genesis of the tumours.…”