The objective of this trial is to study the efficacy of treatment of human papilloma virus (HPV) related oropharyngeal cancer with chemotherapy followed by Transoral Robotic Surgery (TORS) as definitive treatment. Current treatment of oropharyngeal cancer are chemo-radiotherapy. There is significant lifelong side effects associated with this approach related to tissue effects of radiotherapy. The side effects results in significant quality of life deterioration among the patients. Overall there is 20% failure rate with this treatment approach. The study hypothesis is that treatment with upfront (neoadjuvant) chemotherapy followed by transoral surgery and neck dissection is highly effective treatment allowing competitive cure rate compared to chemo-radiotherapy with less than 10% failure rate, while avoiding radiotherapy in majority of cases. It is also hypothesized that better functional and quality of life outcome maybe achieved with this approach.

The current standard of care for advanced (AJCC-7 edition stage III and IV) oropharyngeal squamous cell carcinoma are concomitant chemoradiation, or surgery followed by adjuvant radiation therapy with or without concomitant chemotherapy. These approaches have persistent and significant lifelong side effects and sequelae related to treatment, and in particular related to radiotherapy. The side effects of radiotherapy (augmented with concomitant chemotherapy) include soft tissue fibrosis, loss of salivary function, dry mouth, life long disturbed taste function, poor dental health with rapidly decaying teeth, dysfunction of swallowing, significant loss of the mobility of the base of tongue and pharyngeal constrictors, loss of laryngeal elevation, esophageal stricture, and at times severe side effects such as soft tissue necrosis or osteoradionecrosis of the mandible. About 10% of the patients undergoing chemoradiation for oropharyngeal cancer develop long term swallowing dysfunction with feeding tube dependency. As a result , patient's quality of life (QOL) is adversely affected. Improvements in the side effect profile of treatment, the functional outcome, and the QOL remain very important areas of advancement in treating this patient population. Improvements in functional outcome need to be achieved while maintaining or improving the oncologic outcome and cure rates for cancer, compared to the standard of care.

Use of Taxane based chemotherapy along with Platinum drugs (Cisplatin and Carboplatin) in high dose neoadjuvant setting, coupled with Transoral Laser Microsurgery (TLM) or Transoral Robotic Assisted Surgery (TORS), allows potential for improved oncologic outcome as well as avoidance of long term sequelae of high dose radiation therapy to head and neck. These transoral surgical approaches (TLM and TORS) provide improved functional outcome compared with traditional open composite resections and complex reconstructive algorithms for oropharynx. TLM and TORS are currently in clinical use for early (stage T1 and T2 with N0 or N+ve) oropharyngeal cancer.

De-escalation treatment strategies of TORS followed by adjuvant radiotherapy are being investigated currently. However even without de-escalation there is overall 18-20% rate of treatment failure and half of failures are due to distant metastasis in the absence of loco-regional recurrence. In this study the investigators propose systemic escalation of treatment with neoadjuvant chemotherapy (docetaxel and cisplatin) followed by de-escalated locoregional treatment with transoral surgery and neck dissection reserving radiotherapy for salvage.

This approach has the potential for improved functional outcome by avoiding short and more importantly long term and permanent sequelae of radiation therapy in oropharyngeal cancer treatment. This approach is a new paradigm in treatment of oropharyngeal cancer, and can significantly improve the functional outcome of cancer treatment.

Inclusion Criteria:

• Squamous cell cancer of oropharynx, p 16 positive
• American Joint Commission on Cancer version-7 (AJCC-7) Stage III (T1N1, T2N1, T3N0, T3N1) and stage IVa (T1N2, T2N2, T3N2)
• Treatment Naive
• No evidence of distant metastatic disease
• Fit for surgery, and primary tumor assessed surgically resectable with negative margins via transoral approach
• Age > 18 years
• Karnofsky performance status > 60% or Eastern Cooperative Oncology Group (ECOG) < 2
• Absolute neutrophil count (ANC) > 2,000, platelets > 100,000 and calculated creatinine clearance > 50 cc/min
• Signed study specific consent form
• No other malignancies except cutaneous basal cell carcinoma (BCC) or squamous cell carcinoma (SCC) within the last 5 years
• Agree to use effective contraception while on the study. Women of child bearing potential must have a negative pregnancy test, and not be lactating.

Exclusion Criteria:

• Patients with advanced T4 cancer unresectable without organ preservation
• P16 negative tumor
• N3 disease (Stage IVB AJCC-7)
• 5 or more positive cervical lymph nodes at presentation
• Distant metastatic disease (Stage IVC)
• Radiological evidence of gross extracapsular nodal tumor invasion
• Anatomy not allowing transoral access and exposure
• Prior head and neck cancer at any time (Other than BCC or SCC of skin)
• Coexistent second malignancy or history within 5 years of prior malignancy (other than BCC or early SCC skin or curatively treated Stage I carcinoma of cervix)
• Peripheral neuropathy >/= grade 1
• Have had prior Taxanes or Cisplatin
• Concurrent infection
• Coexisting medical illness of a severity that might interfere with treatment or follow-up, or who do not have the ability to give informed consent.
• Receiving any other investigational agent while on the study