Research Article, J Otol Rhinol Vol: 7 Issue: 2
The Role of Transoral Oropharyngectomy in the Management of Oropharyngeal Cancers
*Corresponding Author : Giridharan Wijayasingam
Locum Consultant ENT Surgeon, Russels Hall Hospital, West Midlands, Address, 102, Kingston Avenue, North Cheam, Surrey, SM3 9UF, UK
E-mail: [email protected]
Received: November 09, 2017 Accepted: February 09, 2018 Published: February 13, 2018
Citation: Wijayasingam G, Gan RWC, Ubayasiri K, Jolly K, Mortimore S, De M, et al. (2018) The Role of Transoral Oropharyngectomy in the Management of Oropharyngeal Cancers. J Otol Rhinol 7:2. doi: 10.4172/2324-8785.1000342
The incidence of oropharyngeal carcinoma is increasing as a result of increasing Human Papilloma Virus (HPV subtypes 16 and 18) infection of the oropharynx. 31 patients with oropharyngeal squamous cell carcinoma were treated in a university teaching hospital. The primary cancer was resected by either transoral laser microsurgery or transoral robotic surgery. Patients underwent simultaneous neck dissection when indicated. The Multidisciplinary Team (MDT) decided whether patients required postoperative radiotherapy/ chemoradiotherapy depending on tumour and patient factors. Survival was analyzed using a Kaplan-Meier estimator. The results were discussed alongside a literature search on oropharyngeal carcinoma management. 87.4% patients were disease free at 1 year, and 77.2 % at both 3 and 5 years. Overall survival at 1 year was 92% and 76.4% at both 3 and 5 years.
Keywords: Oropharyngeal carcinoma; Human Papilloma virus type 16; Transoral laser microsurgery (TLM); Transoral robotic surgery (TORS)
There is an increasing incidence of oropharyngeal carcinoma (OPC) globally, which is due to increase in HPV infection [1,2]. OPC includes malignant neoplasms occurring in the base of tongue, lingual tonsil, soft palate, uvula, palatine tonsils and posterior pharyngeal wall [3,4]. OPCs are most commonly squamous cell carcinomas and can be broadly divided into HPV positive and negative tumours.
Risk factors for OPC include smoking and high alcohol consumption. Human papilloma virus HPV16 causes HPV-positive (p16-positive) oral and oropharyngeal cancers . p16, itself, is a tumour suppressor protein, which is upregulated in HPV positive oropharyngeal carcinoma. HPV positivity of an oropharyngeal tumour is conferred by testing for upregulated levels of p16. Sexual behaviour is the risk factor in HPV positive cases but not smoking or alcohol consumption [6,7]. The population attributable fraction (PAF) of HPV in OPC is about 26% worldwide but appears to be higher, about 50% in North America, Japan and Australia [8,9]. Men have a greater proportion of HPV-positive OPCs compared to women .
Over the last 20 years, there has been a shift in the treatments offered for OPC . Surgical treatment used to involve open resection requiring lip split and mandibulotomy and was associated with significant morbidity, from the year 2000, there was a shift towards chemoradiotherapy instead of surgery . Chemoradiotherapy, however, had its own side effects. Over the past 10 years transoral surgery with the laser or robot has gained popularity as good clearance rates are now achievable whilst avoiding the morbidity of open surgery or primary chemoradiotherapy . Increased survival rate from OPC is due to the increase in the proportion of p16-positive OPC as it carries a better prognosis [2,11].
The aim of this study was to analyze the oncologic and survival outcomes of patients who had undergone transoral surgery for OPC.
Retrospective studies of all cases of OPC treated with primary transoral partial oropharyngectomy performed by 2 consultant surgeons were undertaken. Information was obtained from operating theatre records, electronic and paper patient case notes.
Ethical approval was not required as transoral laser microsurgery (TLM), and transoral robotic surgery (TORS) are established treatments for oropharyngeal cancer at our institution.
All patients were staged via panendoscopy (thorough examination under general anaesthesia of upper aero digestive tract) and CT imaging. Management was discussed in in the MDT setting prior to surgical treatment. Where TLM or TORS was recommended, this was always with curative intent. Palliative patients were excluded from the study.
As for the operative procedure, TLM was performed using the Acublade CO2 laser using the Steiner technique  with a transtumoural approach to cancer resection. For TORS, the Da Vinci robot was used with resection of the cancer en bloc using monopolar diathermy. HPV status was determined from histopathological specimens by p16 immunohistochemistry .
Analysis of locoregional control, disease-free survival and diseasespecific survival were performed using Kaplan-Meier analysis.
31 patients underwent primary transoral resection of oropharyngeal cancer. Subsite location is shown in Table 1. Of these, 39% (n=12) were HPV 16 positive (Table 2).
|Tumour subsite||Number of patients (%)|
|Palatine tonsil||12 (39)|
|Tongue base||11 (36)|
|Posterior pharyngeal wall||4 (13)|
|Soft palate||1 (3)|
|Tongue base & soft palate||1 (3)|
|Palatine tonsil and posterior pharyngeal wall||1 (3)|
|Palatine tonsil and uvula(2 primaries)||1 (3)|
Table 1: Oropharyngeal cancer subsites.
Table 2: T and N classification and HPV16 status of patients.
10 patients were smokers, 5 never smoked and 16 patients had no smoking history recorded in their medical notes. 6 patients were heavy drinkers (more than 42 units of alcohol per week), 6 patients drank between 1 and 42 units weekly, 5 patients did not drink alcohol and 14 patients had no alcohol history documented in their notes. Of the 31 patients, 7 (22.6%) had stage I disease, 3 (9.7%) stage II, 6 (19.4%) stage III, and 15 (48.3%) stage IV (Table 2). 25 patients were treated with transoral laser microsurgery (TLM), of which 1 patient underwent TLM alone, 4 underwent TLM with neck dissection, 2 underwent TLM with chemoradiotherapy, 10 underwent TLM with both neck dissection and chemoradiotherapy and 8 underwent TLM with neck dissection and radiotherapy (Table 3).
|Transoral laser microsurgery (TLM) only||1||0||0||0|
|TLM+ neck dissection||2||2||0||0|
|TLM+chemotherapy and/or radiotherapy||0||0||0||2|
|TLMS+neck dissection+ chemo and/or radiotherapy||6||6||6||0|
|Transoral robotic surgery (TORS) only||1||0||0||0|
|TORS+ chemotherapy and/or radiotherapy||0||1||0||0|
|TORS+neck dissection +chemotherapy and/or radiotherapy||1||0||0||0|
Table 3: Treatment of 31 patients with oropharyngeal cancer.
6 patients were treated with transoral robotic surgery (TORS). 1 patient had TORS alone, 3 patients had TORS with neck dissection, 1 had TORS with chemoradiotherapy and 1 had TORS with bilateral neck dissection and chemoradiotherapy (Table 3).
5 patients required gastrostomy feeding at some point postsurgery and 3 patients had temporary tracheostomies inserted at the time of primary surgery.
19% (n=6) of these resections had positive margins after initial surgery. All these patients went on to have further resection which yielded negative margins.
The percentage of patients disease free at 1 year was 87% (standard error (SE) 7%) and 77% (SE 9%) at both 3 and 5 years (Figure 1). 4 patients had recurrence, among them 1 died prior to MDT discussion, 1 underwent palliative treatment, 1 was treated with chemoradiotherapy and 1 underwent neck dissection followed by chemoradiotherapy. Overall survival of patients at 1 year was 92% (SE 6%) and 76.3% (SE 9.4%) at both 3 years and 5 years post primary surgery (Figure 2). Disease specific survival at 1 year was 95% (SE 4.9%) and 83.5% (SE 8.8%) at both 3 yrs and 5 yrs (Figure 3).
16% (n=5) patients developed postoperative complications. 1 patient developed secondary bleeding and aspiration pneumonia post TORS resection of tonsillar carcinoma. 1 patient had reactionary bleeding post TORS resection of tonsillar carcinoma. 2 patients developed hospital acquired pneumonia post operatively, one having had TLM resection of a tongue base tumour with temperory tracheostomy and the other having had TLM resection of tonsillar tumour and ipsilateral modified neck dissection. 1 patient developed regional lymphoedema post transoral endoscopic laser resection of the left tonsil and soft palate.
Mean patient follow up was 5 years, during which 7 (23%) patients died. 4 of these patients had locoregional recurrences and subsequently died from their disease. 1 patient had a synchronous lung primary and died from this. 1 patient died from a myocardial infarction and 1 patient from post-operative secondary bleeding who was found to have significant cardiac disease.
Samuel et al.  discussed several studies with similar outcomes. They have highlighted a multicentre study of Haughey et al.  consisting of 204 patients treated with transoral laser microsurgery alone or with neck dissection and adjuvant radiotherapy having a 3-year overall survival of 86%, disease specific 88%, disease free 82% .
There is evidence to suggest that transoral surgery offers benefit over chemoradiotherapy in terms of post treatment morbidity. There is preliminary evidence showing that transoral surgery is associated with good early swallowing outcomes at 3 months compared to patients treated with chemoradiotherapy . There is a clinical and cost benefit in TORS for partial pharyngectomy and posterior partial glossectomy . Unfortunately, in our study 20 out of 25 (80%) patients treated with transoral laser surgery (TLM) and 2 out of 6 (33.3%) patients who underwent transoral robotic surgery (TORS) still needed postoperative adjunctive non-surgical treatment in the form of radiotherapy or chemotherapy. However, with further experience of these techniques in our centre, it is hoped that this number can be significantly reduced. We also recognize the incomplete smoking and alcohol histories gathered in the medical notes.
In the RTOG trial (Multi-institutional Trial of Accelerated Hypofractionated Intensity-Modulated Radiation Therapy for Early Stage Oropharyngeal Cancer (RTOG 00-22)) T1 and T2, N0-N1 M0 oropharyngeal cancers were treated with moderately accelerated hypofractionated IMRT (Intensity-Modulated Radiation Therapy) without chemotherapy. High tumour control rates and reduced salivary toxicity were observed compared with similar patients in previous RTOG studies. Major target under-dose deviations were associated with lower loco regional control . Current chemoradiotherapy regimens lead to good long term survival but have long term toxicity, especially affecting swallowing function. Post-operative Adjuvant Treatment for HPV-positive Tumours (PATHOS) is a phase II/III trial looking at reducing the intensity of adjuvant therapy after minimally invasive transoral surgery for oropharyngeal cancer (T1-T3, N0-N2b). The hope is that this will result in improved long term swallowing function whilst maintaining improved long term disease free survival . Once the trial is completed it may lead to treatment with reduced morbidity in patents with HPV positive oropharyngeal carcinoma.
The De-ESCALaTE (Determination of Cetuximab Versus Cisplatin Early and Late Toxicity Events in HPV+ OPSCC) randomised control trial examined less toxic therapy for low risk oropharyngeal carcinoma patients. It compared early and late toxic events in low-risk HPV positive oropharyngeal cancer patients treated with cetuximab versus cisplatin. Though the result of this study may take some time yet, it may lead to a change in treatment protocols, with decreased morbidity .
Transoral robotic assisted surgery (TORS) carries a small, but significant, risk of life-threatening postoperative hemorrhage. In a retrospective review, Mandal et al.  reported 9.8% of 224 patients suffering varying degrees of postoperative haemorrhage. While prophylactic transcervical arterial ligation did not reduce the incidence of postoperative haemorrhage, it did reduce the severity of the bleed.
In a selected group of patients with OPC, transoral laser or robotic surgery is a valid treatment with low morbidity and comparable outcomes compared to chemoradiotherapy.
This retrospective study, although relatively small, suggests that in selected OPC P16-positive patients, transoral laser or robotic surgery can often eliminate the need for adjuvant therapy and its associated toxicity. Current ongoing research on adjuvant therapy may also lead to similar outcomes.
This article does not contain any studies with human participants performed by any of the authors.
Ethical approval was not required as transoral laser microsurgery (TOLMS), transoral endoscopic surgery (TOLES) and transoral robotic surgery (TORS) are established treatments for oropharyngeal cancer at our institution. Written informed consent for each procedure was obtained from patients.
- Chaturvedi AK, Anderson WF, Lortet-Tieulent J, Curado MP, Ferlay J, et al. (2013) Worldwide trends in incidence rates for oral cavity and oropharyngeal cancers. J Clin Oncol 31: 4550-4559.
- Chaturvedi AK, Engels EA, Pfeiffer RM, Hernandez BY, Xiao W, et al. (2011) Human papillomavirus and rising oropharyngeal cancer incidence in the United States. J Clin Oncol 29: 4294-4301.
- Barnes L (2005) Pathology and genetics of head and neck tumours, IARC, USA.
- Combes JD, Franceschi S (2014) Role of human papillomavirus in non-oropharyngeal head and neck cancers. Oral Oncol 50: 370-379.
- Herrero R, Castellsagué X, Pawlita M, Lissowska J, Kee F, et al. (2003) Human papillomavirus and oral cancer: the International Agency for Research on Cancer multicenter study. J Natl Cancer Inst 95: 1772-1783.
- Applebaum KM, Furniss CS, Zeka A, Posner MR, Smith JF, et al. (2007) Lack of association of alcohol and tobacco with HPV16-associated head and neck cancer. J Natl Cancer Inst 99: 1801-1810.
- Schwartz SM, Daling JR, Doody DR, Wipf GC, Carter JJ, et al. (1998) Oral cancer risk in relation to sexual history and evidence of human papillomavirus infection. J Natl Cancer Inst 90: 1626-1636.
- de Martel C, Ferlay J, Franceschi S, Vignat J, Bray F, et al. (2012) Global burden of cancers attributable to infections in 2008: a review and synthetic analysis. Lancet Oncol 13: 607-615.
- Giuliano AR, Nyitray AG, Kreimer AR, Pierce Campbell CM, Goodman MT, et al. (2015) EUROGIN 2014 roadmap: Differences in human papillomavirus infection natural history, transmission and human papillomavirus‐related cancer incidence by gender and anatomic site of infection. Int J Cancer 136: 2752-2760.
- Sheahan P (2015) Changing paradigms for oropharynx cancer: swinging of pendulum back towards surgery. Irish medical journal.
- Ang KK, Harris J, Wheeler R, Weber R, Rosenthal DI, et al. (2010) Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med 363: 24-35.
- Steiner W (1993) Results of curative laser microsurgery of laryngeal carcinomas. Am J Otolaryngol 14: 116-121.
- Girard N (2014) Evidence appraisal of Zhang W, Li N, Chen S, Tan Y, Al-Aidaros M, Chen L. The effects of a tourniquet used in total knee arthroplasty: a meta-analysis. J Orthop Surg Res. 2014;9(1):13. AORN J 100: 224-228.
- Helman SN, Schwedhelm T, Kadakia S, Wang Y, Schiff BA, et al. (2015) Transoral Robotic Surgery in Oropharyngeal Carcinoma. Arch Pathol Lab Med 139: 1389-1397.
- Haughey BH, Hinni ML, Salassa JR, Hayden RE, Grant DG, et al. (2011) Transoral laser microsurgery as primary treatment for advanced-stage oropharyngeal cancer: a United States multicenter study. Head Neck 33: 1683-1694.
- O'Hara J, Cosway B, Muirhead C, Leonard N, Goff D, ver O’Hara, et al. (2015) Transoral laser microsurgery ± adjuvant therapy versus chemoradiotherapy for stage III and IVA oropharyngeal squamous cell carcinoma: Preliminary comparison of early swallowing outcomes. Head Neck 37: 1488-1494.
- Chung TK, Rosenthal EL, Magnuson JS, Carroll WR (2015) Transoral robotic surgery for oropharyngeal and tongue cancer in the United States. Laryngoscope 125: 140-145.
- Eisbruch A, Harris J, Garden AS, Chao CK, Straube W, et al. (2010) Multi-institutional trial of accelerated hypofractionated intensity-modulated radiation therapy for early-stage oropharyngeal cancer (RTOG 00-22). Int J Radiat Oncol Biol Phys 76: 1333-1338.
- Owadally W, Hurt C, Timmins H, Parsons E, Townsend S, et al. (2015) PATHOS: a phase II/III trial of risk-stratified, reduced intensity adjuvant treatment in patients undergoing transoral surgery for Human papillomavirus (HPV) positive oropharyngeal cancer. BMC Cancer 15: 602.
- Mehanna HM, McConkey CC, Hartley AG, Fulton-Lieuw MT, Grumett J, et al. (2016) De-ESCALaTE: Comparison of early and late toxic events in low-risk HPV positive oropharyngeal carcinoma patients treated with chemoradiotherapy, cetuximab versus cisplatin. 2016: TPS6103-TPS6103.
- Mandal R, Duvvuri U, Ferris RL, Kaffenberger TM, Choby GW, et al. (2016) Analysis of post–transoral robotic-assisted surgery hemorrhage: Frequency, outcomes, and prevention. Head Neck 38: E776–E782.