Human Papillomavirus Associated Oropharyngeal Carcinoma-Diagnosis and Management

Head and neck squamous cell carcinomas arise from the mucosa of the upper aerodigestive tract and is often driven by risk factors like tobacco and alcohol consumption. Most of the time patients present with locally advanced stages and the outcome is poor, despite recent advances in multi-modality treatment. The epidemiology of the disease has changed over the last decade with the introduction of a separate clinical entity; Human Papillomavirus (HPV) associated head and neck cancer. The tumorigenesis is different from that of tobacco and alcohol-driven malignancies. These tumors have a better response to treatment owing to their inherent genetic makeup and carry an excellent prognosis. The current school of thought is to reduce the long-term morbidities associated with various treatment modalities, as these patients tend to survive longer. The best management of HPV-associated oropharyngeal cancer is under active investigation

Chemotherapy in Nasopharyngeal Carcinoma

Nasopharyngeal carcinoma is a unique disease entity among head and neck cancers due to its epidemiology and clinical behavior. Non-keratinizing or undifferentiated carcinoma is the most common histological type in endemic areas. Radiotherapy is the treatment for early-stage disease. With the widespread use of IMRT, loco-regional control has improved significantly in locally advanced diseases. But distant metastasis continues to be the most common pattern of failure. To address this issue, chemotherapy has been incorporated into radiotherapy in various settings; as concurrent, induction, and adjuvant. The initial trials of concurrent chemotherapy incorporated adjuvant chemotherapy also and the magnitude of benefit contributed by each treatment was not clear. Later trials proved that adjuvant chemotherapy was not beneficial. Induction chemotherapy when added to concurrent chemoradiation resulted in improvement in Failure Free Survival, Overall Survival, and Distant Metastasis Free Survival. Thus, induction chemotherapy followed by concurrent chemoradiation became the standard of care for locally advanced disease (stage III and IVA). The role of chemotherapy in stage II disease is still evolving. Metastatic nasopharyngeal carcinoma is treated by platinum doublet chemotherapy, Cisplatin-gemcitabine is the standard regimen

Systemic Therapy in Thyroid Cancer

The standard treatment for patients with differentiated thyroid cancer (DTC) is a combination of surgery, radioactive iodine (RAI), and long-term thyroid hormone–suppression therapy. Treatment of patients whose diseases persist, recur, or metastasize remains a challenge. The role of cytotoxic chemotherapy in the treatment of thyroid cancer is limited. The key signaling pathways involved in the pathogenesis of thyroid cancers are the RAS/RAF/MEK & PI3K/Akt/mTOR pathways. Systemic therapy in thyroid cancer involves the use of tyrosine kinase inhibitors targeting the above mentioned pathways which are often both effective in controlling disease and have manageable toxicity. Sorafenib and lenvatinib are approved for advanced radioiodine refractory and poorly differentiated thyroid cancers and vandetanib and cabozantinib for recurrent or metastatic medullary thyroid cancers. Cabozantinib is also approved for the treatment of locally advanced or metastatic radioactive iodine–refractory differentiated thyroid cancer that has progressed after prior VEGF-targeted therapy. The combination of dabrafenib (BRAF inhibitor) and trametinib (MEK inhibitor) is approved for BRAF V600E mutated unresectable locally advanced anaplastic thyroid cancer. Selpercatinib, RET kinase inhibitor is used for advanced and metastatic RET mutated medullary thyroid cancers and advanced and metastatic RET fusion-positive thyroid cancers of any histologic type. Various clinical trials using newer molecules targeting the aforementioned pathways are ongoing

Role of Organ Preservation in Locally Advanced Hypopharyngeal Carcinoma

Hypopharyngeal carcinoma is relatively rare and has the worst prognosis of all head and neck cancers. Initially, surgery followed by postoperative radiation was the standard of care for locally advanced disease. In the recent years, various organ sparing approaches have evolved. There are mainly two schools of thought regarding larynx preservation in hypopharyngeal cancers which include either induction chemotherapy followed by response assessment for radical radiotherapy or concurrent chemoradiation. An ongoing trial is comparing the effectiveness between these two established approaches. The role of anti-EGFR therapy and immunotherapy is still being evaluated. Despite all the advancements in treatment, hypopharyngeal cancers are still associated with poor treatment outcomes