The study demonstrates the immense potential of transcriptional profiling of tumors. Pathways responsible for the carcinogenic processes can be identified through the expression of the proteins observed in transcriptome analysis.
Z. Wang et al.14 demonstrated that genetic polymorphisms in p53-related genes (MDM2, MDM4, p53, p73) in combination with HPV16 increased the risk of oropharyngeal cancer. In their latest study, they have shown p53 and p73 to be important biomarkers of HPV-associated oropharyngeal cancer. Genomic DNA was extracted from the blood of 309 oropharyngeal cancer patients. The p53 genetic variant (Arg/Pro+Pro/Pro) was significantly associated with HPV16 positive tumor [OR 1.9, 95% confidence interval (CI), 1.1–3.3]. The same was observed with p73 (GC/AT+AT/AT) in association with HPV16 positive tumor (OR 2.1, 95% CI, 1.2–3.8). Additionally, the variants, in combination, associate significantly with HPV16 (OR 3.2, 95% CI, 1.4–7.4). This significant association was observed mainly in never-smokers, and older white men. A large sample size is required, however, to validate these findings.15
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Research in Denmark has shown HPV-positive oropharyngeal cancer to have a distinct microRNA (miRNA) profile, which can be utilized in the future as a diagnostic test.16 A group in the United Kingdom compared the efficacy of diagnostic tests to detect the presence of HPV in oropharyngeal cancer. The analysis compared the existing diagnostic tests [RNA qPCR, DNA qPCR, p16 immunohistochemistry (IHC), and high-risk HPV in situ hybridization (ISH)] individually or in combination to determine the test with greatest efficacy. The combination of p16 IHC/DNA qPCR provided a specificity of 94% and a sensitivity of 97% in detecting HPV16 in tumor samples compared to the current gold standard, RNA qPCR.17
Treatment
Standard treatments of HPV-associated oropharyngeal cancer include surgery, intensity-modulated radiation therapy (IMRT), and combined chemotherapy and radiation therapy (CRT), either individually or in combination. Recent research in treatment aims at improving survival rate, increasing target specificity, and decreasing patient discomfort.18
Transoral robotic surgery (TORS) has been used to successfully remove oropharyngeal tumors. A study conducted at the Mayo Clinic in Rochester, Minnesota treated 66 oropharyngeal tumor patients with TORS, and followed them post-surgery for at least two years. The survival rate was greater than 95%, and patients spared of the debilitating effects of standard surgery — cutting and reshaping the tongue, neck, and jawbone and difficulty in swallowing — were able to resume eating orally within three weeks. The favorable outcome was observed predominantly in HPV-positive oropharyngeal tumor patients.18
Initial data from a clinical trial, conducted by the Hofstra-North Shore Long Island Jewish School of Medicine and the Feinstein School of Medical Research, have shown the benefit of adaptive radiotherapy (ART) in treating head and neck cancer patients. Standard intensity-modulated radiotherapy does not take into account changes occurring in tumor size, weight loss, or movement of normal cells. Twenty-two patients who were treated with ART were analyzed, with a median follow up of 31 months. Patients showed excellent remission rates, with an estimate of 100% and 95% for local and regional disease respectively, at the end of two years. Adaptive radiotherapy is a break away from IMRT, wherein computed tomography (CT) scans of patients taken after the first IMRT are used to adapt the next phase of treatment. The first phase of ART used an algorithm to map the contours of the anatomical region close to the oropharynx. The mapped contours were overlaid on the initial baseline IMRT scan to detect tumor shrinkage and change in volume. The first ART plan is calculated for the initial contours of the anatomical region selected for IMRT. The second ART plan is calculated for the daily images generated with radiotherapy resulting in a lower radiation dose targeted toward the appropriate tumor region. Patients with the first ART plan showed a 5% reduction in tumor volume, while the second ART plan showed a 14% reduction in tumor volume. With ART, there are fewer treatment modalities for the patient, and the tumor is successfully targeted. ART preserved basic functions of swallowing and speech in patients by 20 months. The reduction in tumor volume was significant (P<0.0001) compared to baseline high-risk tumor volume. This study also demonstrated a means of personalizing treatment to each specific patient. Although there is no significant difference between the two treatments on acute toxicity, longer follow-up periods of patients will determine the precise effect of ART.19
