Adjuvant Treatment Deintensification After Transoral Surgery for Human Papillomavirus-Positive Squamous Cell Carcinoma of the Oropharynx

Oropharyngeal squamous cell carcinoma (OPSCC) has seen a dramatic rise in incidence over the last two decades. This is largely due to the increased incidence of human papillomavirus-positive (HPV+) malignancy within the oropharynx. In fact, HPV-positive (HPV+) OPSCC has surpassed cervical cancer as the most common HPV related malignancy in the United States. Thus, with the current widespread prevalence of HPV infection, OPSCC will continue to be a major factor in cancer treatment in the national healthcare landscape for years to come.

Fortunately, patients with HPV+ OPSCC have substantially improved treatment response and overall survival (OS) compared to those with HPV-negative malignancy. Prior surgical procedures to remove tumors within the oropharynx were very invasive and highly morbid, requiring face and neck incisions along with mandibulotomy and pharyngotomy approaches. Therefore, treatment paradigms shifted to favor concurrent chemoradiation as the primary treatment modality over primary surgery. However, the acute and long-term toxicity of chemoradiation can be significant, including swallow dysfunction, speech disturbance, taste disturbance, mucositis, xerostomia, fibrosis, osteoradionecrosis, neutropenia, neurotoxicity, and dental disease. With improved survival rates associated with HPV+ OPSCC, more patients are surviving their disease and experiencing these side effects, negatively impacting quality of life (QOL).

With early studies establishing the more favorable prognosis associated with HPV+ OPSCC9, the staging system for OPSCC was completely changed, with HPV+ OPSCC given its own separate system from its HPV negative counterpart. Even with higher nodal burden, HPV+ OPSCC has lower stages, reflecting improved treatment response of this disease. Notably, this reclassification omitted extranodal extension (ENE) as a component of the N staging.

The advent of transoral robotic surgery (TORS) via the da Vinci Surgical System, and other minimally invasive techniques, has reaffirmed surgical therapy as a primary treatment option, as these approaches provide quicker recovery times and confer less morbidity to patients. The safety and oncologic efficacy of TORS has been well-established for the treatment of OPSCC. For example, in one large multi-institutional study of 410 patients undergoing TORS, the 2-year locoregional control rate was 91.8%, disease-specific survival rate 94.5%, and overall survival 91%13. Now, the majority of patients undergo surgery for T1-T2 disease (82%) in the United States according to an analysis of the National Cancer Data Base.

The goal of primary surgical therapy is to minimize long term toxicity by eliminating the need for chemotherapy, decreasing radiation intensity to adjuvant doses, and in some cases, obviating the need for adjuvant therapy altogether while still providing equivalent or even superior oncologic results compared to standard chemoradiation. The resulting effects are improvement in functional outcomes and QOL for patients surviving their disease. The prevailing treatment philosophy within head and neck oncology is that further deintensifying treatment could still provide equivalent oncologic outcomes, while further lowering toxicity profiles and improving functional outcomes even more. There are now numerous trials investigating deintensification in an attempt to minimize the morbidity incurred by patients, and strategies have varied greatly. But still, there is no level I evidence for deintensification, and certainly, no consensus on the best strategies for treatment moving forward in the near future.