Human Papillomavirus as a Marker of the Natural History and Response to Therapy of Head and Neck Squamous Cell Carcinoma
Section snippets
Changing Epidemiology of Head and Neck Cancer
HNSCC is one of several cancers that are strongly associated with tobacco use.4 As presented by Giovino5 in an overview article and illustrated in Figure 1A, smoking of manufactured cigarettes accounted for 1% of all tobacco consumed in the United States in the 1880s, but this form of use increased progressively to about 80% by 1950 when overall annual tobacco consumption peaked at about 13 pounds per person per year. After mounting evidence of the association between tobacco use and lung
Emergence of HPV-Associated Oropharyngeal Carcinoma
The role of some of HPV types, most notably HPV16 and HPV18, in the pathogenesis of cancer of the uterine cervix has been recognized for over 2 decades (reviewed by zur Hausen9, 10). It is now accepted that carcinogenic effects are mainly mediated through 2 high-risk HPV oncoproteins, E6 and E7, which inactivate the tumor protein 53 (TP53) (also referred to as protein 53 [p53]) and retinoblastoma tumor suppressor gene products, respectively,11, 12 thereby disrupting cell cycle regulatory
Histology
There has not been a uniform terminology for reporting of HPV-associated oropharyngeal carcinoma until recently. Histologically, HPV-associated oropharyngeal carcinomas have been misinterpreted as poorly differentiated carcinomas based on the immature appearance of tumor cells or often described as “basaloid” carcinoma based on the lobular growth of cells with hyperchromatic nuclei and a high nuclear to cytoplasmic ratio. A recent study showed that the “basaloid” subtype consists of a mixed
Case Control Series
Several single institutional, retrospective series published about a decade ago suggested that patients with HPV-positive oropharyngeal carcinomas have much better prognosis than those with HPV-negative tumors (Table 1). Most of these early series used PCR-based methods to detect the presence of HPV.
Mellin et al,46 for example, assayed pretreatment biopsies from 60 patients with primary tonsillar carcinomas, treated with radiotherapy alone (45%) or combined with surgery (55%), for presence of
Interaction Between HPV Status and Tobacco Consumption
The rather large sample size of the RTOG series and the systematic data collection enabled assessment of the interaction between tumor HPV status and smoking.42 Of the 206 patients with HPV-positive oropharyngeal carcinoma, 59 (29%) and 110 (53%) were never smokers or were former smokers, respectively. The corresponding numbers for the 117 patients with HPV-negative oropharyngeal tumor were 14 (12%) and 54 (46%), respectively. The median pack-years of tobacco smoking were 12.2 (range: 0-152)
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