2017 Section 7 Green Book

HPV-negative and HPV-positive patients had distinct

independent predictors of survival. The most important

predictor of survival in HPV-negative patients was the

presence of ECS. On the other hand, survival in HPV-

positive patients was associated with the surgical

approach (transoral vs open), and whether or not negative

margins were achieved. Specifically, in the HPV-positive

cohort, those with transoral resection tended to have more

favorable outcomes; patients resected via the open

approach were over 3 times more likely to die than those

treated transorally. When controlling for all factors,

including T classification, smoking status, etc., patients

who underwent transoral resection had improved survival.

Our multivariable analysis confirmed that the surgical

approach was a significant independent predictor of over-

all survival and not simply a surrogate marker for

advanced disease. This finding may reflect the greater

morbidity and swallowing dysfunction associated with

open approaches, placing these patients at greater risk of

postoperative aspiration pneumonia. Without randomiza-

tion to surgical approach, however, potential unidentified

confounders cannot be ruled out.

RPA of the entire patient population revealed that HPV

status was the major determinant of overall survival. In

HPV-positive patients, the next most important determi-

nant of survival was the surgical approach utilized fol-

lowed by the pathologic factors of margin status and

perineural invasion. In the HPV-negative patient popula-

tion, the surgical approach was not a significant predictor

of outcome, but rather the presence of ECS, followed by

the T classification of the primary tumor. If the RPA trees

are pruned further, 3 survival outcome groups emerge

that may be deemed: low-, intermediate-, and high-risk

(see Figure 2). HPV-positive patients who are resected

transorally have the lowest risk of death (15 deaths out of

124 patients; 87.9% survival). For HPV-positive patients

undergoing transoral resection, the presence of perineural

invasion was a significant prognostic factor, as shown in

Figure 2A, which is contrary to the study by Haughey

and Sinha,

who did not find perineural invasion to be a

significant prognostic factor in surgically treated p16-

positive patients. The intermediate-risk group consists of

those patients who are HPV-positive and resected with an

open approach and negative margins (60.3% survival),

HPV-negative patients with no ECS (58.2% survival), or

HPV-negative T1/T2 tumors with ECS (45.5% survival).

Finally, the high-risk group consists of HPV-positive

tumors resected with an open approach and positive mar-

gins (25.0% survival) and HPV-negative T3/T4 tumors

with ECS (13.8% survival).

To complement the survival data, functional outcomes

were also investigated. As shown in Table 4, patients

undergoing an open approach had much higher rates of

gastrostomy tube dependence compared with patients

undergoing a transoral approach. Patients with T1 and T2

tumors who underwent a transoral resection had a gastros-

tomy tube present at 1 year in 7.84% of the cases, regard-

less of HPV status. These numbers are remarkably similar

to other surgical trials and reinforce that higher rates of

gastrostomy tube presence are primarily seen with T3 and

T4 tumors (9.52% for the transoral approach and 33.33%

for the open approach). This number compares favorably

to gastrostomy tube and dysphagia rates in chemoradia-

tion trials. Best et al

reported a 19% rate of stricture

and Shiley et al

reported that 47% of patients continue

to require gastrostomy tube feedings even 1 year after

chemoradiotherapy. Even in studies evaluating the use of

intensity-modulated radiotherapy, sparing pharyngeal con-

strictors, 4 of 73 patients (5.6%) report significant change

in diet and 1 of 73 patients (1.3%) was exclusively gas-

trostomy tube dependent. In quality of life surveys, a

sharp deterioration of swallowing is seen postchemoradio-

therapy treatment and this improves slightly between 3

and 12 months posttherapy. Only 15.6% of patients

reported a normal diet at 1 year postchemoradiotherapy,

57% have objective swallowing impairment, and 23%

exhibit silent aspiration on modified barium swallowing

studies.

In this patient cohort, postoperative concurrent chemo-

radiotherapy was delivered for “high-risk patients” as

defined by the paired

New England Journal of Medicine

manuscripts published in 2004.

34,41

Based on our analysis,

when controlling for other variables, there was no signifi-

cant difference in survival between patients treated with

postoperative radiation versus those treated with concur-

rent chemoradiation. With the recent emphasis on treat-

ment deintensification for HPV-positive patients, transoral

surgery with postoperative radiotherapy alone may be an

effective strategy to pursue based on these results. On the

other hand, patients with HPV-negative tumors, T3/T4

primary, and ECS have unusually poor outcomes from

both a survival and functional perspective. Intensification

of nonsurgical therapy may be the best treatment options

to consider in this group of patients.

The retrospective nature of this study could lend to

selection biases, such as changing treatment patterns and

techniques. Another weakness of this study was the lack

of data on disease-specific, progression-free, and disease-

free survival. However, this study is the largest analysis

of primary surgical therapy for oropharyngeal SCC. We

were able to control for many factors to arrive at the sig-

nificant results of this study, demonstrating excellent sur-

vival and functional outcomes for selected populations

and treatment modalities of oropharyngeal SCC. This

analysis further supports the future use and study of pri-

mary surgical therapy for certain cohorts of oropharyngeal

SCC, particularly in our attempts at deintensifying ther-

apy for HPV-positive patients.

REFERENCES

1. Chaturvedi AK, Anderson WF, Lortet–Tieulent J, et al. Worldwide trends

in incidence rates for oral cavity and oropharyngeal cancers.

J Clin Oncol

2013;31:4550–4559.

2. Gillison ML, D’Souza G, Westra W, et al. Distinct risk factor profiles for

human papillomavirus type 16-positive and human papillomavirus type 16-

negative head and neck cancers.

J Natl Cancer Inst

2008;100:407–420.

TABLE 4. Percentage of patients with gastrostomy tube present at 12

months postsurgery.

Surgical approach

T1/T2

T3/T4

Transoral

7.84%

9.52%

Open

34.0%

33.33%

URGICAL MANAGEMENT OF OROPHARYNGEAL

SCC

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