The incidence of oropharyngeal squamous cell carcinoma (OPSCC) has been steadily increasing over the last few decades, mostly due to HPV, which is now associated with the majority of newly diagnosed cases of OPSCC.
Joshua D. Waltonen, MD
Assistant Professor of Otolaryngology
Comprehensive Cancer Center
Wake Forest Baptist Medical Center
Christopher A. Sullivan, MD
Associate Professor of Otolaryngology
Wake Forest Baptist Medical Center —
Comprehensive Cancer Center
The incidence of oropharyngeal squamous cell carcinoma (OPSCC) has been steadily increasing over the last few decades, mostly due to HPV, which is now associated with the majority of newly diagnosed cases of OPSCC. If current trends continue, projections indicate that HPV-related OPSCC may constitute the majority of all head and neck cancers by the year 2025. These patients are likely to be nonsmokers and are typically younger, with higher education levels and socioeconomic status than tobacco-related OPSCC patients.
Long-term data indicate that HPV-related OPSCC has better survival rates than tobacco-related OPSCC, especially in advanced stages (III and IV).
In previous decades, therapy for advanced OPSCC involved a composite surgical resection, followed by adjuvant radiotherapy (RT) or chemoradiotherapy (CRT). This surgery was quite morbid, involving facial incisions, division or removal of the mandible, and disarticulation of the tongue and pharyngeal muscles. Reconstruction utilized insensate pedicled or microvascular flaps. Long hospitalizations, need for tracheotomy and gastrostomy tubes, and poor speech and swallowing outcomes were typical and expected following these surgeries. Poor functional outcomes were only intensified by side effects of adjuvant therapy.
In the early 1990s, concurrent chemotherapy and radiotherapy for definitive treatment of laryngeal cancers proved successful and was adapted to treat advanced-stage OPSCC. This strategy allowed high cure rates and retained organ function in many patients, without the disfigurement and disability of traditional open surgical procedures. With the onset of the HPV-related OPSCC epidemic, survival rates exceeded 75%. However, long-term toxicities of definitive CRT, including xerostomia, tissue fibrosis, osteoradionecrosis, dysphagia, and g-tube dependence rates of 10% to 40%, reduced overall long-term quality of life.
The rise in popularity of definitive CRT for OPSCC carried with it recognition of long-term associated swallowing dysfunction and encouraged the development of several minimally invasive surgical approaches, in which exposure was achieved transorally using a headlight or microscope, and tumors were resected using endoscopic instrumentation and CO2 lasers. Drawbacks of these approaches included difficult exposure, poor lighting, and inability in some cases to adequately remove the posterior or inferior extent of tumors. The learning curve for these techniques was steep and expertise was limited to a few centers nationwide.
To address some of the shortfalls of existing minimally invasive techniques, a new transoral approach to the oropharynx was developed at the University of Pennsylvania beginning in 2006, using the daVinci surgical robot (Intuitive Surgical, Sunnyvale, California). Traditional transoral approaches lacked adequate lighting and exposure of distal oropharyngeal locations; thus, the robot, with its stereoscopic, high-definition display and articulating arms, provided the perfect tool to approach oropharyngeal cancers.
Transoral robotic surgery (TORS) involves inserting a camera into the mouth to provide illumination and visualization, with two miniature arms on either side of the camera that manipulate and divide tissue. These arms are controlled by the surgeon at a remote console, translating the surgeon’s large arm and hand movements at the console into fine, precise actions in the mouth. TORS eliminated some of the difficulties presented by the earlier minimally invasive approaches and quickly gained momentum nationwide as the ease of use became recognized and favorable initial results were published.
Generally speaking, contraindications to minimally invasive surgery for OPSCC include unresectable neck nodes, deep invasion of the parapharyngeal space or tongue base, >50% involvement of the tongue base or posterior pharyngeal wall, involvement of the carotid artery, invasion of the mandible, or inability to expose the tumor completely (either due to patient or tumor factors).
The long-term survival results and functional outcomes from these minimally invasive surgical approaches have recently been published from the first few centers to adopt these strategies, and appear to compare favorably to definitive RT or CRT. Expectations are that the results from the next wave of centers to implement TORS as the initial therapy for OPSCC will be forthcoming soon, including outcomes from our institution.
A controversial concept in the treatment of OPSCC (especially HPV-related) is “de-intensification” of therapy. That is, can the toxicities of CRT be reduced by the elimination of chemotherapy and/ or the decrease of radiation doses from definitive to adjuvant levels, without compromising oncologic results? Studies have shown that following minimally invasive surgery, chemotherapy can be avoided in 50% to 74% of cases, depending on the surgical pathology results.
An unresolved question that needs further study is comparison of the oncologic and functional outcomes of TORS plus RT/CRT to definitive CRT. Future avenues of research include the upcoming multicenter randomized trials (RTOG 1221 and ECOG 3311) investigating the use of these strategies.
Like these studies, all future analyses should include not only oncologic outcomes, but also functional and quality-of-life data. With early studies demonstrating what appears to be excellent oncologic efficacy from both the surgical and nonsurgical strategies, treatment decisions will have to take into account the expected functional outcomes and toxicities.