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Squamous cell carcinoma arises from multiple anatomic subsites in the head and neck region. The risk factors for development of cancers of the oral cavity, oropharynx, hypopharynx, and larynx include tobacco exposure and alcohol dependence, and infection with oncogenic viruses is associated with cancers developing in the nasopharynx, palatine, and lingual tonsils of the oropharynx. The incidence of human papillomavirus–associated oropharyngeal cancer is increasing in developed countries, and by 2020, the annual incidence could surpass that of cervical cancer. The treatment for early-stage squamous cell cancers of the head and neck is generally single modality, either surgery or radiotherapy. The treatment for locally advanced head and neck cancers is multimodal, with either surgery followed by adjuvant radiation or chemoradiation as indicated by pathologic features or definitive chemoradiation. For recurrent disease that is not amenable to a salvage local or regional approach and for metastatic disease, chemotherapy with or without a biological agent is indicated. To date, molecular testing has not influenced treatment selection in head and neck cancer. This review will focus on the changing epidemiology, advances in diagnosis, and treatment options for squamous cell cancers of the head and neck, along with data on risk stratification specific to oropharyngeal cancer, and will highlight the direction of current trials.

A rise in incidence of oropharyngeal squamous cell cancer—specifically of the lingual and palatine tonsils—in white men younger than age 50 years who have no history of alcohol or tobacco use has been recorded over the past decade. This malignant disease is associated with human papillomavirus (HPV) 16 infection. The biology of HPV-positive oropharyngeal cancer is distinct with P53 degradation, retinoblastoma RB pathway inactivation, and P16 upregulation. By contrast, tobacco-related oropharyngeal cancer is characterised by TP53 mutation and downregulation of CDKN2A (encoding P16). The best method to detect virus in tumour is controversial, and both in-situ hybridisation and PCR are commonly used; P16 immunohistochemistry could serve as a potential surrogate marker. HPV-positive oropharyngeal cancer seems to be more responsive to chemotherapy and radiation than HPV-negative disease. HPV 16 is a prognostic marker for enhanced overall and disease-free survival, but its use as a predictive marker has not yet been proven. Many questions about the natural history of oral HPV infection remain under investigation. For example, why does the increase in HPV-related oropharyngeal cancer dominate in men? What is the potential of HPV vaccines for primary prevention? Could an accurate method to detect HPV in tumour be developed? Which treatment strategies reduce toxic effects without compromising survival? Our aim with this review is to highlight current understanding of the epidemiology, biology, detection, and management of HPV-related oropharyngeal head and neck squamous cell carcinoma, and to describe unresolved issues.

Head and neck cancers account for less than 5% of all cancers and for less than 3% of all cancer deaths in the United States. The populations at risk for head and neck cancers are those who have a long-standing history of smoking and alcohol use. More recently, the incidence of oropharyngeal cancer in younger populations has been increasing and is associated with exposure to the human papillomavirus. This subset of patients appears to have a better overall prognosis and to respond better to treatment. This review is limited to head and neck cancers of squamous cell histology, which constitute more than 90% of head and neck cancers. Because treatment of head and neck cancers is complex and involves multiple modalities, a multidisciplinary approach is needed. This review focuses on the goal of organ preservation and postoperative treatment of high-risk patients with the concurrent use of chemotherapy and radiation therapy. This review also highlights recent advances in treatment using molecularly targeted therapies, specifically the role of inhibitors of the epidermal growth factor receptor in locally advanced and recurrent/metastatic squamous cell cancer of the head and neck. Studies in the English language were identified by searching the MEDLINE, EMBASE database (1980-2007) using the search terms head and neck, squamous cell, carcinoma, chemotherapy, radiation, human papillomavirus, epidermal growth factor receptor, and targeted therapy.

Introduction. Cutaneous paraneoplastic syndromes are a heterogeneous group of skin manifestations that occur in relation to many known malignancies. Paraneoplastic occurrence of SCLE has been noted but is not commonly reported. SCLE association with cholangiocarcinoma is rare. Case Presentation. A 72-year-old man with a history of extrahepatic stage IV cholangiocarcinoma presented with a pruritic rash. Cholangiocarcinoma had been diagnosed three years earlier and was treated. Five months after interruption of his chemotherapy due to a semiurgent surgery, he presented with explosive onset of a new pruritic rash, arthralgias, and lower extremity edema. Physical exam revealed a scaly erythematous rash on his arms, hands, face, neck, legs, and trunk. It was thick and scaly on sun exposed areas. Skin biopsy revealed vacuolar interface dermatitis. Immunofluorescence revealed IgM positive cytoid bodies scattered along the epidermal basement membrane zone. PET-CT scanning revealed metabolically active recurrent disease in peripancreatic and periportal region with hypermetabolic lymph nodes. Oral steroids and new regimen of chemotherapy were started. Rash improved and steroids were tapered off. Discussion. Paraneoplastic syndromes demonstrate the complex interaction between the immune system and cancer. Treatment resistant SCLE should raise a suspicion for paraneoplastic etiology.

Head and neck cancers account for less than 5% of all cancers and for less than 3% of all cancer deaths in the United States. The populations at risk for head and neck cancers are those who have a long-standing history of smoking and alcohol use. More recently, the incidence of oropharyngeal cancer in younger populations has been increasing and is associated with exposure to the human papillomavirus. This subset of patients appears to have a better overall prognosis and to respond better to treatment. This review is limited to head and neck cancers of squamous cell histology, which constitute more than 90% of head and neck cancers. Because treatment of head and neck cancers is complex and involves multiple modalities, a multidisciplinary approach is needed. This review focuses on the goal of organ preservation and postoperative treatment of high-risk patients with the concurrent use of chemotherapy and radiation therapy. This review also highlights recent advances in treatment using molecularly targeted therapies, specifically the role of inhibitors of the epidermal growth factor receptor in locally advanced and recurrent/metastatic squamous cell cancer of the head and neck. Studies in the English language were identified by searching the MEDLINE, EMBASE database (1980-2007) using the search terms head and neck, squamous cell, carcinoma, chemotherapy, radiation, human papillomavirus, epidermal growth factor receptor, and targeted therapy.

A rise in the annual incidence of oropharynx squamous cell cancer, specifically the lingual and palatine tonsils, in white men under the age of 50, non-smokers and non-alcoholics, has been observed over the past decade. This entity is associated with human papilloma virus-16 infection and the risk factors include an increased number of oral and vaginal sex partners at a younger age. The biology of HPV-related oropharynx cancer is distinct with p53 degradation, Rb pathway inactivation, and p16 upregulation. This is in contrast to tobacco related oropharynx cancer which is characterized by p53 mutation and downregulation of p16. The optimal method to detect virus in tumor is controversial and both in situ hybridization and PCR are commonly used; p16 immunohistochemistry may serve as a potential surrogate marker. HPV-related oropharynx cancer appears to be more responsive to chemotherapy and radiation than HPV negative orpharynx cancer. HPV-16 is a prognostic marker for improved overall survival and disease-free survival but has not yet been shown to be a predictive marker. Investigators continue to explore unanswered questions regarding the natural history of oral HPV infection, why the increase dominates in men, the potential of HPV vaccines for primary prevention, developing a commercially available accurate method to detect the virus in tumor, and treatment strategies that reduce toxicity without compromising survival. The goal of this review is to highlight our current understanding of the epidemiology, biology, detection, as well as current management and unresolved issues of HPV-related oropharyngeal HNSCC.

Medical oncologists have traditionally had little to offer patients with metastatic radioactive iodine-resistant thyroid cancer. The 3-year survival rate of patients with differentiated thyroid cancer is less than 50%, with little response obtained from standard cytotoxic chemotherapies. In recent years, however, huge advances have been made in understanding the molecular pathways and cellular pathogenesis of this disease. This knowledge has in turn led to the development of a range of targeted therapies, some specific to thyroid cancer genetic alterations such as the RET/PTC translocation, and others that exploit general malignant properties such as angiogenesis. This review highlights novel targeted agents for the treatment of differentiated and medullary thyroid cancers being studied at this time, and the results of recently published trials. We propose that such patients should be managed, whenever possible, within a clinical trial, in order to access the most promising new drugs for thyroid cancer. In cases where trials are unavailable, we recommend off-label use of the currently available oral multikinase inhibitors such as sorafenib and sunitinib rather than traditional chemotherapies.

TAS‐106, a RNA polymerase inhibitor, was studied in solid tumors with potential clinical benefit and reasonable tolerability. We conducted a multicenter, international phase II trial of TAS‐106 in salvage metastatic or recurrent head and neck squamous cell cancer (HNSCC) and nasopharyngeal cancer (NPC) patients. TAS‐106 monotherapy was given at 6.5 mg/m2 over 24‐h continuous infusion every 3 weeks. Translational studies for blood and tissue were included. Twenty‐seven enrolled patients experienced the most common drug‐related adverse events of neutropenia, fatigue, non‐neutropenic fever, injection site reaction, and skin rash/dermatitis. The greater than or equal to grade 3 adverse events included neutropenia (14.8%), febrile neutropenia (7.4%), pneumonia (7.4%), and peripheral neuropathy (3.7%). The overall response rate was 0% in both subgroups; five HNSCC patients had stable disease (median duration 99 days) and four NPC patients had stable disease (median duration of 92.5 days). Median progression‐free survival (PFS) for HNSCC patients was 52 days (95% CI 43.0–99.0 days) and 48 days (95% CI 41.0–83.0 days) for NPC. Median overall survival (OS) for HNSCC patients was 175 days (95% CI 92.0–234.0 days) and 280 days (95% CI 107.0–462.0 days) for NPC. The TAS‐106 plasma levels were equivalent between Asian and Caucasian patients. There was no significant correlation of tumor UCK2 protein expression levels to TAS‐106 efficacy. TAS‐106 was reasonably tolerated in patients with platinum‐failure HNSCC and NPC. The administration schedule of 24‐h continuous infusion prevented neurologic toxicity, but had myelosuppression as its main toxicity. There was no anti‐tumor efficacy seen with TAS‐106 monotherapy. Future studies will focus on TAS‐106 combinations and mechanisms of drug resistance. TAS‐106 was reasonably tolerated in patients with platinum‐failure HNSCC and NPC with the 24‐h continuous infusion administration schedule; however, there was no anti‐tumor efficacy seen with TAS‐106 monotherapy. Future studies will focus on TAS‐106 combinations and mechanisms of drug resistance.