Human papillomavirus-16 in oral squamous cell carcinoma: Clinical correlates and 5-year survival

https://doi.org/10.1016/j.bjoms.2006.04.012Get rights and content

Abstract

We examined 66 oral squamous cell carcinomas (OSCCs) for human papillomavirus-16 (HPV-16) infection to evaluate its prognostic significance. Cox regression analysis of 5-year survival demonstrated that patients without nodal metastasis or with intratumoural HPV-16 showed better prognoses compared with each counterpart. In Kaplan-Meier survival analysis, nodal status but not HPV-16 status was statistically significant. The 5-year survival rate of HPV-16 positive patients without nodal metastasis (94%) was extremely high, compared with that of HPV-16 negative patients with nodal metastasis (25%). These results suggest that HPV-16 status as well as nodal status may provide prognostic significance in patients with OSCC.

Introduction

Numerous studies have been done to investigate the role of HPVs, particularly high-risk genotypes, in anogenital and head and neck cancers.1, 2, 3, 4, 5 These studies have indicated that oncogenic HPVs have a causal relationship with cervical carcinomas,1, 2 but that the relationship with OSCCs is less well-defined.3, 4, 5 To investigate the exact relationship of HPVs with OSCCs, Miller et al.4 performed a meta-analysis and concluded that oral infection with HPV, particularly with high-risk genotypes, was considered to be a significant independent risk factor for OSCC. In addition, recent molecular studies have suggested that infection of HPVs may promote head and neck carcinogenesis.6, 7

After several studies suggesting that HPV status may affect the prognoses of patients with cervical cancers, similar investigations have been performed in patients with head and neck cancers. However, the results have been inconclusive so far.8, 9, 10, 11, 12, 13, 14, 15, 16 In some of these studies, OSCCs were not separated from other head and neck cancers, and specific HPV types were not examined. Furthermore, other confounding factors to influence prognoses of cancer patients were not considered in analyses. In order to clarify the exact relationship of intratumoural HPV status to the prognoses of OSCC patients, here we retrospectively investigated the association of intratumoural HPV-16 with clinicopathologic and background variables, and 5-year survival of Japanese OSCC patients in the Hiroshima district, because these subjects have advantages to exclude race or area difference in HPV prevalence.

Section snippets

Patients and data classification

Sixty-six Japanese patients diagnosed as OSCC between 1992 and 1999 were enrolled in this study. Their records were collected from the files of Department of Oral and Maxillofacial Reconstructive Surgery in Hiroshima University Hospital. Pathological material for analysis was obtained from the primary tumours at the time of biopsy. Specimens were fixed in 10% neutral formalin and embedded in paraffin, and then were histologically examined. Verrucous carcinomas were excluded from this study.

Patients’ characteristics

The characteristics of the study population are summarized in Table 1. Patients’ ages ranged from 40 to 91 years (mean: 67.5 years). The male-to-female ratio was about 2 to 1. The study population consisted of 24 drinkers (36%) and 23 smokers (35%). The primary tumour was located in the alveolus/gingiva (n = 27), tongue (n = 18), oral floor (n = 9), buccal mucosa (n = 6), lip (n = 4), or palate (n = 2). Patients in this study comprised a heterogeneous population of disease sites and disease stages.

Discussion

It is well known that HPV-16 is detected in normal oral mucosa as well as oral epithelial dysplasia and OSCC.3, 4, 5 However, the HPV copy numbers in normal oral mucosa is relatively low compared with those in oral epithelial dysplasias and OSCCs.22, 23 Terai et al.23 speculated that the low-level HPV infection in normal oral mucosa is common, but subclinical or latent. On the other hand, the high-level HPV infection in premalignant and malignant conditions is considered to indicate that HPV

Acknowledgements

The authors gratefully acknowledge Dr. N. Maitland, Cancer Research Unit, Dept. of Biology, University of York, UK, for providing SiHa DNA. We thank Drs Tamiko Dohmen and Keiko Sakata for their help in data collection. This work was supported by a grant (No. 16390590) from the Ministry of Education, Sports and Science to Professor Masaru Sugiyama.

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    These authors contributed equally to this work.

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