Received: 14 December 2016

| Revised: 21 April 2017

| Accepted: 15 June 2017
DOI: 10.1002/hed.24887

ORIGINAL ARTICLE

Transoral robotic surgery for tonsillar cancer: Addressing the

contralateral tonsil

Peter T. Dziegielewski, MD, FRCSC1,2 | Brian J. Boyce, MD1 | Matthew Old, MD3,4 |
Theodoros N. Teknos, MD3,4 | Amit Agrawal, MD3,4 | Hafiz Patwa, MD3 |
Enver Ozer, MD3,4

1
Department of Otolaryngology,
Abstract
University of Florida, Gainesville, Florida
2
University of Florida Health Cancer Background: The purpose of this study is to determine the incidence and risk fac-
Center, University of Florida, Gainesville, tors for bilateral tonsillar cancers treated with transoral robotic surgery (TORS) and
Florida to determine the morbidity of the procedure.
3
Department of Otolaryngology - Head
Methods: Patients undergoing TORS for known tonsillar cancer were retrospectively
and Neck Surgery, The Ohio State
University Wexner Medical Center, reviewed. Perioperative variables and surgical outcomes were analyzed to determine
Columbus, Ohio predictive factors for bilateral disease and morbidity rates.
4
Comprehensive Cancer Center, Arthur G. Results: Seventy-nine consecutive patients with tonsillar cancers underwent primary
James Cancer Hospital and Richard J. TORS radical tonsillectomy. Thirty of these patients also underwent contralateral ton-
Solove Research Institute, Columbus,
sillectomy. Three patients (10%) were found to have contralateral tonsillar cancers on
Ohio
final pathology. These were not identified on preoperative positron emission tomog-
Correspondence raphy (PET)-CT or clinical examination. There were no differences in complications,
Peter T. Dziegielewski, Department of gastrostomy tube (G-tube) rates, or length of stay (P > .05). Blood loss was 11.5 cc
Otolaryngology, University of Florida, more in the contralateral tonsillectomy group (P 5 .001).
Room MSB M2-228, 1600 SW Archer
Road, Gainesville, FL 32610.
Conclusion: All patients undergoing primary TORS for tonsillar cancers should also
Email: peter.t.dz@gmail.com undergo contralateral tonsillectomy to optimize oncologic outcomes with no increase
in morbidity.

KEYWORDS
bilateral tonsillar cancer, contralateral tonsillar cancer, tonsillar cancer, transoral robotic surgery (TORS)

1 | INTRODUCTION
“Field cancerization,” a concept dating back to 1953,1 has
withstood the test of time. The theory postulates that multiple
cancers may arise independently in the upper aerodigestive
tract (UADT) because of prolonged exposure to carcinogens,
such as tobacco smoke and alcohol. Second primary malignan-
cies are present in up to 36% of patients with UADT cancer
within 20 years of their original diagnosis.2,3 Synchronous
This work was presented at the International Federation of Head and
Neck Oncologic Societies (IFHNOS) meeting, New York, NY, July 26,
2014.
tumors occur simultaneously with the index cancer and are
present in approximately 4% of cases.4 The oropharynx is one
of the most common sites of synchronous UADT cancers,
with the tonsils being the most common site affected. Over the
past decade, the etiology of oropharyngeal cancers has shifted
toward human papillomavirus (HPV) infection; thus, begging
the question: does field cancerization apply to this new UADT
cancer demographic?
Synchronous primary oropharyngeal cancers are an
emerging observation. Koch et al21 reported a 10% incidence
of bilateral cancers found in the workup of carcinoma of
unknown primary (CUP), which included panendoscopy and
directed biopsies/tonsillectomies. Others have also reported

Head & Neck. 2017;1–8. wileyonlinelibrary.com/journal/hed V

C 2017 Wiley Periodicals, Inc. | 1
2 |
cases of bilateral tonsillar cancers with mechanisms of viral
field cancerization proposed.5 However, the incidence of
bilateral tonsillar cancers in the case of a known tonsillar
cancer is to be determined.
In the era of transoral robotic surgery (TORS), the oppor-
tunity for identifying the source of a CUP6 has increased to
at least 75%. Moreover, using TORS, an increasing amount
of synchronous oropharyngeal cancers may be found.
The purpose of this study is to determine the rate of con-
tralateral tonsillar cancers, when the primary tonsillar cancer
is treated with TORS. Secondary outcomes include measure-
ments of morbidity associated with addressing the contralat-
eral tonsil.
2 | MATERIALS AND METHODS
Institutional review board research ethics approval was
obtained from the Ohio State University Office of Responsi-
ble Research Practices (OSU-07061). The study was con-
ducted at a tertiary care academic comprehensive cancer
center with National Cancer Institute designation.
2.1 | Setting and study design
Patients were enrolled at the Head and Neck Cancer Clinic at
The Ohio State University/Arthur G. James Cancer Hospital
at their first new-patient consultation with a head and neck
surgical oncologist. If the patient had chosen to proceed with
TORS, a study coordinator explained the study, obtained
written informed consent, and registered the patient for the
clinical trial. Baseline data were then collected. All potential
TORS cases were reviewed at a weekly head and neck can-
cer multidisciplinary tumor board before finalizing treatment
plans. The design was a retrospective review of prospectively
collected data from April 2008 to June 2013.
2.2 | Patient selection
The inclusion criteria were: (1) biopsy proven tonsillar squa-
mous cell carcinoma; (2) bilateral tonsils present; (3) clinical
T1-T3 disease; and (4) scheduled for TORS with unilateral
or bilateral tonsillectomy.
The exclusion criteria were: (1) inadequate transoral
exposure to allow for TORS instrumentation; (2) preopera-
tive positron emission tomography (PET)-CT demonstrating
distant metastases; and (3) panendoscopy demonstrating an
unresectable primary tumor or a synchronous second primary
tumor.
The research questions were: (1) What is the rate of syn-
chronous bilateral tonsillar cancer in patients undergoing
TORS for tonsillar cancer?; (2) What factors predict synchro-
nous bilateral tonsillar cancer?; and (3) How do the
DZIEGIELEWSKI ET AL.
perioperative and functional outcomes compare between uni-
lateral radical tonsillectomy (group 1) and unilateral radical
tonsillectomy with contralateral tonsillectomy (group 2)?
2.3 | Treatment
All new patients with head and neck cancer at the Ohio State
University underwent a standard metastatic workup, includ-
ing a CT neck and chest or full body PET-CT and panendo-
scopy.7 Those who chose TORS as a primary treatment for
tonsillar cancer were scheduled for a single-staged proce-
dure, including panendoscopy, TORS radical tonsillectomy,
and neck dissection. A subset of patients underwent contra-
lateral tonsillectomy by 1 of 2 surgeons. It was the prefer-
ence and standard of care for these 2 surgeons to perform
contralateral tonsillectomy in each case. This protocol was
based on experience with locoregional recurrences in contra-
lateral tonsils in several patients as well as a perceived low
morbidity of adding the contralateral tonsillectomy. Thus, for
these surgeons, all patients undergoing a TORS radical ton-
sillectomy for a known tonsillar cancer also underwent a
contralateral tonsillectomy. The indication for the contralat-
eral tonsillectomy was the presence of a contralateral tonsil.
No other patients underwent contralateral tonsillectomy. No
patients were suspected to have cancer in the contralateral
tonsil preoperatively. TORS was performed with the da
Vinci Surgical System (Intuitive Surgical, Sunnyvale, CA)
after panendoscopy.8–10 After radical tonsillectomy, frozen
section margins were sent from all 4 quadrants of the muco-
sal defect and from the deep aspect of the defect. While wait-
ing for pathological reading of the margins, the contralateral
tonsillectomy was performed (if planned). The robot was
then removed from the field and neck dissection was con-
ducted. Ipsilateral neck dissection was performed in all cases.
Contralateral neck dissection was performed when preopera-
tive clinical or radiological suspicion for positive contralat-
eral neck metastases was suspected.
2.4 | Data collection
A clinical trial coordinator collected clinicopathologic data
prospectively as it became available. Preoperative data
included: age at surgery, sex, race, tissue diagnosis, site of
tumor, Charlson Comorbidity Index (CCI), and smoking sta-
tus/pack-year history. Postoperative data included: intraoper-
ative blood loss, histopathological data, adjuvant treatment,
HPV status, protein p16INKa (p16) status, nodal status,
TNM classification, perineural invasion, lymphovascular
invasion, margin status (negative 2 mm), extracapsular
spread, American Joint Committee on Cancer staging,11 peri-
operative complications, hospital length of stay (LOS),
follow-up time, and gastrostomy tube (G-tube) dependence.
DZIEGIELEWSKI ET AL.
All data were retrospectively reviewed via the prospective
database and cross-verified with a medical records review.
The PET scans were reviewed for patients with available
data, and standardized uptake values (SUVs) were deter-
mined for both tonsils.
2.5 | Outcome measures
The primary outcome was rate of bilateral synchronous ton-
sillar cancers in patients undergoing radical tonsillectomy
and contralateral tonsillectomy.
The study population was divided into 2 groups for mor-
bidity analysis: (1) the ipsilateral radical tonsillectomy and
contralateral tonsillectomy group; and (2) the ipsilateral radi-
cal tonsillectomy group.
Secondary outcomes included a comparison of periopera-
tive outcomes (LOS, estimate blood loss, and perioperative
complications) and functional outcomes (need for G-tube
feeding and need for tracheostomy).
2.6 | Statistical analysis
The SPSS 24.0 software package (SPSS, Chicago, IL) was
used for analyses. Continuous variables were compared
using the Mann-Whitney U test, and categorical variables
with a chi-square test. Logistic regression analysis was per-
formed to determine patient and tumor variables that may be
predictive of bilateral tonsillar cancers. All comparisons
were 2-tailed and statistical significance was set as P < .05.
3 | RESULTS
Seventy-nine consecutive patients with tonsillar cancers were
treated with TORS. All patients underwent ipsilateral radical
tonsillectomy and 30 also underwent contralateral tonsillec-
tomy. A summary of patient and pathology characteristics is
shown in Table 1. The median age of patients was 55.6 years
(range 39.2-78.5 years). The median CCI score was 4.0
(range 2-12). Smokers had a median history of 37.5 pack-
years (range 8-100 pack-years). The median number of
lymph nodes in neck dissection specimens was 33.0 nodes
per side (range 11-87 nodes). The median number of positive
nodes was 1.0 (range 0-9 nodes). No patients received head
and neck radiotherapy (RT) before surgery. Sixty-six patients
(83%) received postoperative RT and 42 (53%) received
postoperative chemoradiotherapy. Patients were followed for
a median of 10.5 months (range 0-42.3 months).
Of these 30 patients who underwent bilateral tonsillec-
tomy, 3 were found to have bilateral tonsillar cancers. Their
case specifics are shown in Table 2. All patients with bilat-
eral cancers underwent ipsilateral neck dissection and RT to
both sides of the neck postoperatively. The radiation fields
| 3
included both tonsils and both sides of the neck with doses
of 60-66 Gy to the tonsils and 54-60 Gy to the neck. Case 1
had a low volume pT2 contralateral cancer measuring 2.3 3
0.8 3 0.5 cm, which was confined to the tonsillar tissue.
There was no invasion of adjacent muscles. This cancer was
not picked up on panendoscopy as the tonsil was endophytic
and minimally firm. Preoperative imaging did not show any
anatomic signs of cancer in this tonsil and the SUV was 3.8
lower than the ipsilateral side.
Table 3 demonstrated the clinical and functional out-
comes of both groups of patients. The median hospital LOS
for all patients was 4.0 days (range 1-30 days). Figure 1
shows an example of a PET-CT for case 1. All contralateral
tonsils did not show any clinical or radiologic suspicion for
invasive carcinoma. Case 1 was particularly peculiar as the
tumor was endophytic and soft. The tumor measured 2.3 cm
in the greatest dimension and was confined within the tonsil-
lar tissue; thus, it could not be easily detected before patho-
logic analysis. The complications encountered included 1
postoperative hemorrhage in each group; both occurred on
the radical tonsil side and required a trip back to the operat-
ing room for cautery. Two cases of aspiration pneumonia
occurred in each group. There were no instances of circum-
ferential oropharyngeal scarring in either group. Seven
patients required a G-tube at some point during their treat-
ment. One patient in each group was using a G-tube at last
follow-up. All other G-tube users had their tubes removed
before the last follow-up.
Preoperative CT scans were available for all patients. No
scans showed any suspicious findings in the contralateral
tonsils. The PET-CT scans were available for 19 patients.
The median SUV for ipsilateral tonsils was 9.4 (range 3.7-
21.3) and for contralateral tonsils was 6.4 (range 3.5-11.7).
There was no significant difference in these values (P 5
.25). The median SUV for positive contralateral tonsils was
3.8 (range 3.5-10.8).
Univariate and multivariate regression analyses were per-
formed on all variables collected to identify predictors of
contralateral tonsillar cancer (Table 4). No variables were
significant predictors of bilateral tonsillar cancers (P > .05).
4 | DISCUSSION
Approximately 16 cases of bilateral tonsillar cancers have
been reported in the literature.12–19 The vast majority of these
have been CUP scenarios. To date, no prior study has
described the incidence of bilateral tonsillar cancers in the
scenario of a known tonsillar cancer. The incidence of syn-
chronous UADT cancer has been estimated to be under
5%20; however, this figure has been postulated to be higher
for oropharyngeal cancers.21 The rational is 2-fold: (1) the
higher percentage of CUP with synchronous tumors,15,21 as
4 | DZIEGIELEWSKI ET AL.

T A BL E 1 Patient characteristics

Group 1
Ipsilateral radical tonsillectomy Group 2
1 contralateral tonsillectomy Ipsilateral radical tonsillectomy
Variables No. of patients (%) No. of patients (%) P value

No. of pa- 49 30
tients

Sex .93
Male 23 (77) 38 (78)
Female 7 (23) 11 (22)

Age, years .34

55 17 (57) 33 (67)
<55 13 (43) 16 (33)

Race .02
White 27 (90) 49 (100)
African 3 (10) 0 (0)
American

CCI .002
4 20 (67) 46 (94)
<4 10 (33) 3 (6)

Smokers .03
Yes 22 (73) 45 (92)
No 8 (27) 4 (8)

Tumor site .29

Tonsils 27 (90) 47 (96)
Glosso- 3 (10) 2 (4)
tonsillar
sulcus

pT .63
T1 14 (17) 17 (22)
T2 14 (17) 27 (34)
T3 1 (1) 4 (5)
T4 1 (1) 1 (2)

pN .89
Nx 0 (0) 1 (2)
N0 2 (7) 3 (6)
N1 6 (20) 5 (10)
N2a 6 (20) 13 (27)
N2b 13 (43) 22 (45)
N2c 1 (3) 2 (4)
N3 2 (7) 3 (6)

Overall .63
stage
I 1 (3) 2 (4)
II 1 (3) 0 (0)
III 5 (17) 5 (10)
(Continues)
DZIEGIELEWSKI ET AL.
| 5

T A BL E 1 (Continued)

Group 1
Ipsilateral radical tonsillectomy Group 2
1 contralateral tonsillectomy Ipsilateral radical tonsillectomy
Variables No. of patients (%) No. of patients (%) P value
IV 23 (77) 41 (86)

PNI .89
Present 10 (33) 15 (32)
Absent 20 (67) 32 (68)

LVI .80
Present 13 (43) 19 (40)
Absent 17 (57) 28 (60)

ECS .81
Present 11 (37) 16 (34)
Absent 19 (63) 31 (66)

Margin sta- .18

tus
Positive 6 (12) 1 (3)
Negative 43 (8) 29 (97)

p16 status .88

Positive 26 (87) 35 (85)
Negative 4 (13) 6 (15)

HPV status .29

Positive 20 (67) 32 (78)
Negative 10 (33) 9 (22)

Abbreviations: CCI, Charlson Comorbidity; ECS, extracapsular spread; HPV, human papillomavirus; LVI, lymphovascular invasion; p16, protein cyclin-dependent
kinase inhibitor 2A / protein p16INKa; pN, pathological neck node classification; PNI, perineural invasion; pT, pathological tumor classification of ipsilateral
cancer.
Figures in boldface indicate statistical significance.

well as (2) the oropharynx being a broad based, high
surface-area contact point for carcinogens, such as tobacco
smoke and HPV. This study has shown that 10% of known
tonsillar cancers will have a sister cancer in the contralateral
tonsil.
All 3 patients with bilateral tonsillar cancer were fairly
young white men with early tonsillar squamous cell carcino-
mas. Two of three cases were p16-positive. This is consistent
with previous case reports of similar patients.12–19 The risk
factor profiles suggest that both smoking and HPV infection
may predispose patients with tonsillar cancer to bilateral dis-
ease. The carcinogenesis mechanism of tobacco smoke is
well known and has been shown to increase the odds of
developing a second primary UADT cancer by 2.9-fold.2,22
The mechanism of HPV-induced synchronous cancers is
hypothesized to occur by one of 3 models: (1) a single HPV
infection transforms multiple cells at neighboring locations;
(2) multiple HPV infections occur simultaneously, and (3)
aberrant oncogene expression in one tumor results in trans-
formation of a clone, which migrates to a neighboring loca-
tion to form a second cancer.5 The odds of developing
concurrent HPV-related tonsillar cancers are difficult to dis-
cern, as the exposure to the virus is not always known.
Identifying a synchronous tonsillar cancer can dramati-
cally alter treatment. Consideration of treating the contralat-
eral tonsil and neck must be taken into account when this
scenario is encountered. In the current series, both patients
with HPV-positive disease required adjuvant RT to the con-
tralateral oropharynx and neck, which was not planned
based on preoperative clinical examination and imaging. In
these cases, bilateral TORS proved valuable in prescribing
the correct treatment. Patients undergoing only an ipsilateral
radical tonsillectomy did not receive RT to the contralateral
tonsil. It is possible that not knowing the oncologic status of
both tonsils may undertreat patients with occult contralateral
disease.
6 | DZIEGIELEWSKI ET AL.

T A BL E 2 Patients with bilateral tonsillar cancers seen in the tonsils, with physiologic values in the range of
1.5-4.0.25 Tonsils with cancer have higher values of 9.36 6
Characteristics Case 1 Case 2 Case 3
4.5425 in previous studies and 9.40 6 5.41 in this study.
Age, years 54.6 49.0 46.7 Although, negative tonsils tend to have lower SUVs com-
Sex Male Male Male
pared with positive ipsilateral ones in this study and previous
data,25 the positive contralateral tonsils were found have a
Race White White White lower median SUV of 3.8. This is counterintuitive and dem-
CCI 3 3 2 onstrates that the contralateral tonsil may exhibit metabolic
activity at physiologic levels. This second cancer may be
Smoking history, 40 53 0 more indolent and could be missed on imaging and clinical
pack-years
examination. This is particularly true for endophytic cancers
HPV status Negative Positive Positive confined to the tonsils. Only pathological analysis will iden-
tify these second cancers.
p16 status Negative Positive Positive
Unfortunately, no predictive factors were found on
PET SUV, 14.2 / 10.8 3.7 / 3.5 7.1 / 3.8 regression analysis for bilateral tonsillar cancer. Thus, it is
ipsilateral tonsil / argued that contralateral disease should be suspected in all
contralateral tonsil
tonsillar cancers until proven otherwise.
pT, ipsilateral 2 1 2 When performing a radical tonsillectomy using TORS,
some surgeons may avoid a contralateral tonsillectomy for
pT, contralateral 2 1 1
fear of increased complications. Fear of increased pain,
pN, ipsilateral 2a 0 2b bleeding, circumferential scarring, and functional impairment
have all been cited as reasons to avoid contralateral tonsillec-
cN, contralateral 0 0 0
tomy in these cases.26 In this study, it was shown that the
PNI 1 1 0 surgical outcome in patients undergoing TORS radical tonsil-
LVI 0 1 1 lectomy, with or without contralateral tonsillectomy, are
equally good. The hospital LOS, complication rates, and G-
ECS 0 1 0 tube rates are low and similar to the results of previous stud-
Margins ies looking at TORS radical tonsillectomy.27 The only out-
come, which differed between the groups, was blood loss,
Ipsilateral tonsil Negative 1 mm Negative
which was, on average, 11.5 cc more in the contralateral ton-
Contralateral tonsil Negative Negative Negative sillectomy group. Although this difference was statistically
significant (P 5 .001), it is not considered clinically
Adjuvant treatment XRT CRT XRT
significant.
Hospital LOS, days 4 4 4 The limitations of this study are within its retrospective
Complications None None None
nature. Only 30 patients underwent bilateral tonsillectomy;

G-tube None None None

T A BL E 3 Clinical and functional outcomes
Follow-up time, mo 21.4 14.8 10.7

Abbreviations: CCI, Charlson Comorbidity Index; CRT, chemoradiotherapy; Ipsilateral radical

ECS, extracapsular spread; G-tube, gastrostomy tube; HPV, human papilloma- tonsillectomy 1 Ipsilateral
virus; LOS, length of stay; LVI, lymphovascular invasion; PET, positron emis- contralateral radical
sion tomography; pN, pathological neck node classification; PNI, perineural Variables tonsillectomy tonsillectomy P value
invasion; pT, pathological tumor classification of ipsilateral cancer; SUV,
standardized uptake value; XRT, external beam radiotherapy. Median EBL, 25 (3-100) 13.5 (2-200) .001
mL (range)

Median LOS, 4.0 (1-30) 4.0 (1-8) .12

It would be ideal to identify bilateral tonsillar tumors in days (range)
the pretreatment setting. The PET-CT scans can identify Complications 3 (10%) 3 (6%) .53
CUP in over 50% of patients.23 However, the tonsils pose a
particular challenge. Because the tonsils are located at the G-tube 7 (23%) 10 (21%) .59

junction between the digestive and respiratory tracts, they are Abbreviations: EBL, estimated blood loss; G-tube, need for a gastrostomy at
constantly exposed to inflammatory antigens, leading to some point during treatment; LOS, length of hospital stay.
Figures in boldface indicate statistical significance.
increased cellular metabolism.24 Increased SUVs are often
DZIEGIELEWSKI ET AL.
| 7

bias. However, no patient was suspected to have contralateral

disease. By including the contralateral tonsillectomy in all
patients undergoing TORS for tonsillar cancers, a more accu-
rate rate of bilateral disease will be determined. A final point
to consider would be the concept of a “condemned Wal-
deyer’s Ring” in HPV-positive oropharyngeal cancers. If
there is a high incidence of bilateral tonsillar disease, perhaps
the lingual tonsils could also be harboring cancers? This idea
was not tested here, but certainly warrants future
consideration.

5 | CONCLUSION

Ten percent of known tonsillar cancers may harbor contralat-

eral tonsillar carcinoma. Clinical examinations and PET-CT
scans are not reliable in detecting occult contralateral tonsil-
F I G U R E 1 Axial positron emission tomography-CT image of a lar cancers. To improve outcomes with minimal morbidity, it
patient (case 1) with bilateral tonsillar cancers [Color figure can be viewed is recommended that all patients undergoing TORS for
at wileyonlinelibrary.com] known tonsillar cancers also undergo contralateral
tonsillectomy.
however, this is the largest series of patients with known ton-
sillar cancers undergoing such treatment. It is possible that C O NFL IC T O F IN T E RE S T
the number of bilateral tonsillar cancers could be underrepre-
Dr Enver Ozer is a surgical proctor for Intuitive Surgical.
sented. The decision to proceed with contralateral tonsillec-
tomy was based on surgeon preference, which could carry a
R EFE RE NC ES
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How to cite this article: Dziegielewski PT, Boyce BJ,
Old M, et al. Transoral robotic surgery for tonsillar can-
cer: Addressing the contralateral tonsil. Head & Neck.
2017;00:1–8. https://doi.org/10.1002/hed.24887