Orofacial pain onset predicts transition to head and neck cancer

Abstract

Contrary to a clinical aphorism that early head and neck cancer is painless, we show that patients who develop head and neck cancer experience significant pain at the time of initial diagnosis. We compared orofacial pain sensitivity in groups of patients with normal oral mucosa, oral precancer, and newly diagnosed oral cancer. The University of California San Francisco Oral Cancer Pain Questionnaire was administered to these patients at their initial visit, before being prescribed analgesics for pain and before any treatment. In contrast to those with biopsy-proven normal oral mucosa and oral precancer, only oral cancer patients reported significant levels of spontaneous pain and functional restriction from pain. Moreover, oral cancer patients experienced significantly higher function-related, rather than spontaneous, pain qualities. These findings suggest an important predictor for the transition from oral precancer to cancer may be the onset of orofacial pain that is exacerbated during function. Screening patients who have new-onset orofacial pain may lead to a diagnosis of early resectable head and neck cancer and may improve quality of life and survival for head and neck cancer patients.

Figure 1. Oral precancer and oral cancer are clinically indistinguishable

Precancerous lesions such as carcinoma in situ affecting the lateral tongue (A1), floor of mouth (A2), and buccal mucosa (A3) are not distinguishable from their respective squamous cell carcinoma counterparts (B1, B2, and B3) on physical examination alone. Black circles indicate approximate extent of oral lesion.

Figure 2. Oral precancer and oral cancer may be distinguished by histopathological signs of invasion

(A) Normal oral mucosa showing stratified squamous epithelium with normal cytoarchitecture. (B) Precancer (carcinoma in situ) with dysplastic changes extending the entire thickness of the epithelium. The main histopathological sign distinguishing oral precancer (B) from oral squamous cell carcinoma (C) is invasion of dysplastic epithelial cells through the basement membrane into the underlying tissues. Black scale bar = 100μm.

Figure 3. Orofacial pain distinguishes oral precancer from cancer at the time of diagnosis

Mean visual analogue scale pain scores with standard error for each of the eight questions were compared between normal oral mucosa, oral precancer and oral cancer patients. Oral cancer patients experienced marked spontaneous and function-related pain in comparison to the relatively pain-free normal oral (***P<0.001) and oral precancer patients (***P<0.001, RM ANOVA-on-ranks, Dunn’s).