Human papillomavirus infection as a prognostic factor in carcinomas of the oral cavity and oropharynx

Abstract

Although studies have established human papillomaviruses (HPVs) as a risk factor for oral and oropharyngeal cancer, it is not clear whether viral infection affects survival in head and neck malignancies. This investigation examined the relationship between HPV and survival in carcinomas of the oral cavity and oropharynx. Formalin-fixed, paraffin-embedded tumor specimens from 139 newly diagnosed cases were tested for HPVs by PCR and DNA sequencing. Patient and tumor characteristics were obtained from questionnaires, pathology reports and cancer registries. Odds ratios (ORs) and relative risks (RRs) were based on logistic and Cox regression models, respectively. HPVs were detected in 21% of the tumors; 83% were HPV-16. Greater risk of HPV infection was associated with males (OR ‫؍‬ 2.9, 95% CI ‫؍‬ 1.0 -8.6), a history of oral-genital sex (OR ‫؍‬ 4.2, 95% CI ‫؍‬ 1.5-11.7), and oropharyngeal tumors (OR ‫؍‬ 10.4, 95% CI ‫؍‬ 3.5-31.2). As tobacco usage increased, the odds of HPV detection decreased (OR ‫؍‬ 0.97/pack-year, 95% CI ‫؍‬ 0.96 -0.99). HPV infected patients had better overall survival (RR ‫؍‬ 0.3, 95% CI ‫؍‬ 0.1-0.8) than those with HPV-negative tumors. There was an interaction between gender and HPV for overall (p ‫؍‬ 0.05) and disease-specific (p ‫؍‬ 0.03) survival that suggested that HPV infected males had better prognosis than HPVnegative males, but this was not the case among females. HPV status was identified as an independent prognostic factor in oral and oropharyngeal cancers. This result appeared to be gender-specific, suggesting the need for further study of the interaction between HPV and gender on survival.

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

“…Other strong indicators for a favorable prognosis in our study include tumor diameter o4 cm, low/no expression of cyclin D1, and low/no tobacco consumption. In accordance with most other studies on HPV-related oropharyngeal carcinomas, we also found a favorable disease-specific survival in patients with HPV16-positive tonsillar squamous cell carcinomas, 12,46,[60][61][62][63][64] and p14 ARF overexpression, 31 although with less significance than the indicators described above. We noticed that lymph node status, which is generally considered as the most important prognostic factor in head-and-neck squamous cell carcinomas, 23 had little value in our series of tonsillar squamous cell carcinomas, which is in concordance with other studies.…”

“…9 It has been shown that there are several differences between HPV-positive and -negative headand-neck squamous cell carcinomas. Despite the fact that HPV positivity in head-and-neck squamous cell carcinomas is an indicator for favorable prognosis, from a clinical point of view these tumors are often poorly differentiated 4,6,[10][11][12] and metastasized to lymph nodes at presentation. 10,11 Furthermore, HPV-positive tumors are often smaller at first diagnosis (diameter r4 cm), 13 and associated with low/no exposure to alcohol and tobacco.…”

Oral squamous cell carcinoma: Review of prognostic and predictive factors

“…There is escalating evidence of a causal association between HPV and OSCC, [82][83][84][85][86][87][88][89][90][91][92][93] with several studies showing that HPV is associated with increased risk of oral cancer, independently of exposure to tobacco and alcohol. 84,86,88,89 This association is valid for high-risk HPV, which comprises subtypes 16, 18, 33, and 35.…”

“…82,83,94 Recently published data on the prevalence of HPV infection in OSCC points to rates between 15% and 30%, but this might be an underestimation; it may ascend to more than 50%. 84,86,87,89,91 The disparity found in the published data has been associated with variations in collection of samples, the efficiency of the detection procedure, and geographic parameters. It is not well established how HPV infects the upper airway and oral cavity, but epidemiologic evidence suggests sexual transmission, 82,93 because the prevalence of infection increases after the onset of sexual activity, although the presence of HPV in OSCC has not yet been robustly linked to sexual practices such as oral sex.…”

“…To date, the findings have been inconsistent, with some studies reporting no survival differences 84,87,94 and others clearly stating a reduction in death risk among patients with HPVpositive tumors when compared with those with HPVnegative tumors. 82,83,88,[90][91][92] A large study conducted by Gillison et al 82 has shown that patients with HPVpositive tumors had a 60% reduction in risk of death from cancer and significantly improved disease-specific survival when compared patients with HPV-negative tumors. Schwartz et al 90 also found a strong association between the presence of HPV-16 DNA in OSCC and prolonged survival.…”