Survival of squamous cell carcinoma of the head and neck in relation to human papillomavirus infection: Review and meta‐analysis

Abstract

Human papillomavirus (HPV) has been associated with head and neck squamous cell carcinomas (HNSCC), especially of the oropharynx, with highest distribution in the tonsils. HPV infection has been associated with improved outcome, although not all the studies show consistent results. The reason for this is not clear. We reviewed all published articles and conducted a meta-analysis on the overall relationship between HPV infection and overall survival (OS) and disease-free survival (DFS) in HNSCC. Patients with HPV-positive HNSCC had a lower risk of dying (meta HR: 0.85, 95% CI: 0.7-1.0), and a lower risk of recurrence (meta HR: 0.62, 95%CI: 0.5-0.8) than HPV-negative HNSCC patients. Sitespecific analyses show that patients with HPV-positive oropharyngeal tumours had a 28% reduced risk of death (meta HR: 0.72, 95%CI: 0.5-1.0) in comparison to patients with HPV-negative oropharyngeal tumours. Similar observations were made for DFS (meta HR: 0.51, 95% CI: 0.4-0.7). There was no difference in OS between HPV-positive and negative non-oropharyngeal patients. The observed improved OS and DFS for HPV-positive HNSCC patients is specific to the oropharynx; these tumours may have a distinct etiology from those tumours in non-oropharyngeal sites. ' 2007 Wiley-Liss, Inc.Key words: HPV; overall survival; disease-free survival; head and neck cancerThe majority of head and neck tumours are differentiated squamous cell carcinomas (SCC), which occur in the oral cavity, oropharynx, hypopharynx and larynx. Approximately 45,660 new cases and 11,210 deaths from cancers of the oral cavity, pharynx and larynx are expected in the United States in 2007.1 The 5-year relative age-adjusted survival rate for these head and neck sites was 58% between 1973 and 2002 (58% for males and 60% for females), 2 and have remained unchanged for more than 3 decades. This poor survival rate is primarily due to the late stage of diagnosis, and to a high frequency of recurrence and second primary tumours. [3][4][5][6][7] Human papillomavirus (HPV) is associated with the development of most anogenital carcinomas, including cervical cancer and, has more recently been suggested to be a risk factor for a subset of head and neck squamous cell carcinoma (HNSCC).8 Most HPV-associated HNSCC tend to occur in the oropharynx, with highest distribution in the tonsils. HPV16 is the predominant genotype detected in head and neck tumours, with different prevalence between head and neck subsites. A recent review of the prognostic significance of HPV in survival of head and neck cancer patients has shown that the majority of studies have reported better survival in patients with HPV-positive head and neck tumours when compared to patients with HPV-negative tumours.9 However, the same review also reported that in some studies, HPV infection resulted in a worse prognosis or had no influence on prognosis.We have reviewed all published articles that have addresses the impact of HPV infection on the outcome of patients with HNSCC, and have also conducted a meta-analysis of the pub...

Mutation and Transcriptional Profiling of Formalin-Fixed Paraffin Embedded Specimens as Companion Methods to Immunohistochemistry for Determining Therapeutic Targets in Oropharyngeal Squamous Cell Carcinoma (OPSCC): A Pilot of Proof of Principle

“…Part of the reasons behind this phenomenon is the increased incidence of high risk human papillomavirus (HPV) related OPSCC [1][2][3]. Interestingly, multiple retrospective studies have shown that patients with HPVpositive OPSCC have a better prognosis compared to patients with HPV-negative tumors [4,5]. OPSCC accounts for the majority of patients enrolled in therapeutic trials for SCCHN and a growing subgroup of these patients have HPV-related carcinoma.…”

“…It is well known that for patients with OPSCC, the overall survival is substantially better among patients with HPV-positive cancer compared to HPV-negative disease [5,[7][8][9][10]. In one highly cited clinical trial [7], high risk HPV infection status was demonstrated as an independent prognostic variable.…”

Human Papillomavirus-Associated Head and Neck Squamous Cell Carcinoma Survival: A Comparison by Tumor Site and Initial Treatment

“…Human papillomavirus (HPV)-positive head and neck squamous cell carcinoma (HNSCC) is increasingly recognized as a distinct disease associated with improved survival and response to therapy [1][2][3][4]. HPV DNA detected in these tumors (predominantly HPV type 16, the most common high-risk type also found in cervical cancer) is frequently integrated and transcriptionally active, with the majority expressing viral oncoproteins E6 and E7 [5,6].…”

P21Cip1/WAF1 expression is strongly associated with HPV-positive tonsillar carcinoma and a favorable prognosis

“…First, although many studies describe a significant association between HPV presence and favorable prognosis, some studies did not find such a correlation. [20][21][22] Second, HPV has also been identified in head-and-neck squamous cell carcinomas of smokers, significantly reducing its favorable effect on clinical outcome. 13 Furthermore, despite the fact that regional lymph node metastasis is considered as the most important prognostic factor in head-and-neck squamous cell carcinomas, 23 this parameter seems to be unreliable in tonsillar squamous cell carcinomas.…”