Original ResearchHead and Neck Surgery
Otolaryngology
Laryngeal Papillary Squamous Cell
Carcinoma: A Population-Based Analysis
of Incidence and Survival
Rahul Dutta1, Qasim Husain, MD2,3, David Kam1,
Pariket M. Dubal1, Soly Baredes, MD1,4, and
Jean Anderson Eloy, MD1,4,5
No sponsorships or competing interests have been disclosed for this article.
Abstract
Objective. Papillary squamous cell carcinoma has emerged as
a distinct entity from the more common keratinizing squa-
mous cell carcinoma. The basis behind this distinction
relates not only to its histologic variation but also to its
overall prognosis and survival. The objective of this study
was to demonstrate the incidence, demographics, and long-
term survival of laryngeal papillary squamous cell carcinoma
(LPSCC) and how it relates to other laryngeal malignancies
using a population-based database.
Study Design. Analysis of a population-based tumor registry.
Methods. The United States National Cancer Institutes
Surveillance, Epidemiology, and End Results registry was
used to perform a retrospective analysis. Patients diagnosed
with LPSCC from 1973 to 2011 were identified. Data end-
points extracted included patient demographics, incidence,
and survival.
Results. Three-hundred seventy cases of LPSCC were identi-
fied, corresponding to 0.5% of all laryngeal tumors. There
was a 3:1 male predilection, without a significant racial pre-
ference. Most tumors identified were localized (T1) and at
stage 1. The 1-year, 5-year, and 10-year disease-specific sur-
vival (DSS) for LPSCC was 97.1%, 83.1%, and 73.9%, respec-
tively, compared with 87.9%, 64.5%, and 50.5% for other
laryngeal malignancies (P values \.0001). Surgery was asso-
ciated with a higher overall DSS in both LPSCC (87.4% vs
78.8%) and other laryngeal malignancies (70% vs 59.4%)
when compared with other treatment modalities.
Conclusion. This analysis of the largest sample of LPSCC
demonstrates a better prognosis for this pathology com-
pared with other laryngeal malignancies.
Keywords
laryngeal cancer, papillary squamous cell carcinoma, popula-
tion based analysis, SEER, demographic, incidence, survival,
disease-specific survival, relative survival, laryngeal papillary
squamous cell carcinoma.
Head and Neck Surgery
2015, Vol. 153(1) 5459
American Academy of
OtolaryngologyHead and Neck
Surgery Foundation 2015
Reprints and permission:
sagepub.com/journalsPermissions.nav
DOI: 10.1177/0194599815581613
http://otojournal.org
Received December 1, 2014; revised February 20, 2015; accepted
March 23, 2015.
S
quamous cell carcinoma (SCC) accounts for approxi-
mately 90% of malignant laryngeal neoplasms.1
Papillary squamous cell carcinoma (PSCC) is a sub-
type of SCC first identified in the head and neck region by
Parkhill in 1968.2-4 This differentiation is derived from his-
topathology. Microscopically, these tumors exhibit delicate
frondlike projections.5 The papillae have fibrovascular cores
and are lined by dysplastic squamous epithelium. The cells
are predominantly nonkeratinizing and have a high nuclear-
to-cytoplasmic ratio.6 There are 2 growth patterns: exophy-
tic, which is broad-based with bulbous ends, and papillary,
with long, slender, fingerlike projections. Diagnostic criteria
require a tumor for which the papillary/exophytic compo-
nent is at least 50% to 70%.6
Laryngeal PSCC (LPSCC) is predominantly seen in men
and has a strong association with alcohol and tobacco use.2
These cancers in the larynx present with dysphonia, airway
obstruction, sore throat, cough, dysphagia, and hemoptysis.7
These tumors do not usually arise from a preexisting papil-
loma, except in cases of irradiation.6,8-11
1
Department of OtolaryngologyHead and Neck Surgery, Rutgers New
Jersey Medical School, Newark, New Jersey, USA
2
Department of OtolaryngologyHead and Neck Surgery, Columbia
University Medical Center, New York, New York, USA
3
Department of OtolaryngologyHead and Neck Surgery, Weill Cornell
Medical College, New York, New York, USA
4
Center for Skull Base and Pituitary Surgery, Neurological Institute of New
Jersey, Rutgers New Jersey Medical School, Newark, New Jersey, USA
5
Department of Neurological Surgery, Rutgers New Jersey Medical School,
Newark, New Jersey, USA
Corresponding Author:
Jean Anderson Eloy, MD, Professor and Vice Chairman, Director, Rhinology
and Sinus Surgery, Director, Otolaryngology Research, Co-director,
Endoscopic Skull Base Surgery Program, Department of Otolaryngology
Head and Neck Surgery, Neurological Institute of New Jersey, Rutgers New
Jersey Medical School, 90 Bergen St, Suite 8100, Newark, NJ 07103, USA.
Email: jean.anderson.eloy@gmail.com
Dutta et al
Roughly 33% to 50% of head and neck PSCC cases are
positive for human papillomavirus (HPV), with most being
low-risk HPV type 6.12-14 Tumors with HPV involvement
tend to have a better survival.15 Prognosis for LPSCC is
better than typical keratinizing SCC (KSCC); 5-year sur-
vival is 88% for exophytic and 100% for papillary, but
these values are based on studies that use the more stringent
70% cutoff for diagnosis.2,6
Because of its improved prognosis compared with conven-
tional SCC, PSCC has in recent years gained increasing rec-
ognition as a distinct diagnosis. A comprehensive analysis of
a large population may therefore be of interest to otolaryngol-
ogists. This study examines the Surveillance, Epidemiology,
and End Results (SEER) registry to evaluate the incidence of
LPSCC, organized by patient demographics, treatment mod-
alities, and long-term survival trends.
Materials and Methods
The SEER 18 database is an aggregation of data from 18
cancer registries either from states or metropolitan areas
within the United States. There were no patient identifiers
used, and therefore, institutional review board (IRB)
approval was not necessary per the guidelines of the IRB of
Rutgers New Jersey Medical School (Newark, New Jersey).
The SEER 18 database was used to identify patients with
LPSCC between 1973 and 2011, and incidence and survival
data were extracted. The database was searched for malig-
nancies of the larynx. The results were then filtered by the
International Classification of Diseases and Oncology, third
edition (ICD-O-3) codes corresponding to papillary squa-
mous cell carcinoma (8052/3). Data for every laryngeal
malignancy not belonging to the 8052/3 coding for papillary
squamous cell carcinoma were also aggregated and used as
a comparison against LPSCC. These are referred to as
other laryngeal malignancies in this article and represents laryngeal malignances (70% compared with 59.4%; Table
an average of non-LPSCC malignancies of the larynx.
Statistical Analysis
The SEER*Stat 8.1.2 software (National Cancer Institute,
Bethesda, Maryland) was used for analysis. Patient data for
LPSCC were compared with that from other laryngeal
tumors using 2-proportion z tests and Fisher exact tests
(NCSS Statistical Software, Kaysville, Utah). Survival data
exported from SEER were reorganized in Microsoft Excel
2013 (Microsoft Corporation, Redmond, Washington) and
then analyzed for disease-specific survival (DSS) using log-
rank analysis in JMP Statistical Discovery 11 (SAS Institute,
Cary, North Carolina). Data derived from SEER*Stat 8.1.2
were also used to generate relative survival data. Statistical
significance was indicated by a probability value (P value) of
\.05 for all tests.
Results
Patient Characteristics
Three-hundred seventy patients with LPSCC were identified
from 1973 to 2011 using SEER 18, corresponding to 0.5%
of all laryngeal cancers. Males were significantly more
55
represented than females: more than 3 times more (P \
.05). The most commonly afflicted race was white, followed
by black, although the difference was not statistically signif-
icant (P = .3). The most common locations identified were
the glottis and supraglottis. The mean ages of diagnosis for
LPSCC and other laryngeal malignancies were 65.5 years
and 64.3 years, respectively. A significant incidence trend
could not be established for LPSCC (P = .8056), while inci-
dence was decreasing for other laryngeal malignancies (P =
.0006; Table 1).
Tumor Characteristics/Staging
TNM staging was available in 42.9% of the cases (Table
2). T1 cancers were most commonly identified (48.4% of
cases) among those reporting TNM staging. Nodal metas-
tases were uncommon, with 77.4% of cases being N0.
Distant metastasis was rare, identified in 1.3% of cases.
Overall staging was reported in 39.7% of cases, with stage
1 being the most commonly reported at 42.8% (Table 3).
Treatment
Treatments offered included various types of surgery and
radiotherapy (Table 4). Surgery was used as a treatment
modality in 48.6% of cases. The most common surgery
offered was local excision of lesion. Radiotherapy was used
in 70.7% of cases reported.
Survival Analysis
DSS at 1, 5, and 10 years for LPSCC was significantly
higher in the same time period than for all other laryngeal
malignancies (all P values \.0001; Table 5; Figure 1).
The relative survival demonstrated the same trend. DSS
after surgery was higher than without surgery for both
LPSCC (87.4% compared with 78.8%; Figure 2) and other
5). When stratified by staging (stages I/II being low
grade and III/IV being high grade), 5-year DSS survival
for low-grade LPSCC (89.5%) was significantly higher than
high-grade LPSCC (54.6%; Figure 3). The DSS in those
cases in which surgery was not involved was significantly
different in LPSCC compared with other laryngeal malig-
nancies (78.8% compared with 59.4%, P \ .0001).
Discussion
Laryngeal malignancies, specifically squamous cell carcino-
mas of the larynx, have been extensively studied. The most
common type is KSCC. The treatment paradigms and sur-
vival data have been elucidated in the literature with large
multicenter studies.16,17 This does not hold true for rare var-
iants of laryngeal SCC, such as PSCC. The present analysis
was performed to further understand LPSCC with respect to
incidence, treatment, and survival.
PSCC is a distinct variant of SCC, distinguished by its his-
tologic papillary growth pattern consisting of a fibrovascular
core covered by malignant squamous epithelium.8,12,18 This
differs from the more common KSCC, which is characterized
by abundant cytoplasmic keratin intermediate filaments and/
56 OtolaryngologyHead and Neck Surgery 153(1)

Table 1. Patient Demographics.a

Papillary Squamous Cell Other Laryngeal
Characteristic Carcinoma (n = 370) Malignancies (n = 65,155) P Value

Gender
Male 280 52,512 .0173
Female 90 12,643

All races
White 296 53,847 .3030b
Black 57 8934
Other 15 2120
Unknown 2 254
Location
C32.0-Glottis 189 33,974 .6818
C32.1-Supraglottis 147 21,974 .0147
C32.2-Subglottis 7 1,046 .6599
C32.3-Laryngeal cartilage 1 487 .2891
C32.8-Overlapping lesion of larynx 11 2,101 .7872
C32.9-Larynx, not otherwise specified 15 5,573 .0020
Range 22-92 0-103
Median 67 64
Mean 65.5 64.3
Incidencec 0.0238 3.5549
Annual percentage change (2000-2011)c 0.2333 (P = .8056) 0.09514 (P = .0006)
a
Bolded values indicate significance.
b
P value compares blacks and whites.
c
Rates are per 100,000 and age adjusted to the 2000 US Standard Population (19 age groups, census P25-1130) standard.

Table 2. TNM Staging for Laryngeal Papillary Squamous Cell Table 3. Staging for Laryngeal Papillary Squamous Cell Carcinoma.
Carcinoma.
Stage Number Percentage
TNM Stage Number Percentage
1 68 42.8
T1 77 48.4 2 36 22.6
T2 48 30.2 3 21 13.2
T3 18 11.3 4 22 13.8
T4 9 5.7 Unknown 12 7.5
TX 7 4.4
N0 123 77.4
N1 12 7.5
N2 12 7.5
N3 2 1.3 50% of PSCC.6,12 Interestingly, HPV-positive tumors have
N4 0 0.0 been shown to confer a survival benefit (both overall and dis-
NX 10 6.3 ease specific) compared with HPV-negative SCC.15,19 The
M0 149 93.7 exact role of HPV in the pathogenesis of LPSCC has yet to
M1 2 1.3 be defined, and there are not enough data to make conclusive
MX 8 5.0 comments with regard to any survival benefit at this time.
This study demonstrated that LPSCC represents only 0.5%
of all laryngeal cancers. More than 90% of laryngeal cancers
are KSCC. This study also shows the male predilection of
LPSCC (76% in males compared with 24% in females).
or extracellular keratin material.6 Although not investigated The most common location for these tumors based on
by this analysis, the impact of HPV in head and neck SCC is this analysis is the glottis, followed by the supraglottis.
important to be recognized. HPV appears to be associated in TNM staging was available in 42.9% of cases. While only a
40% of head and neck SCCs and has been found in up to fraction of the total cases reported TNM staging, there were
Dutta et al 57

Table 4. Treatment Information. Table 5. Survival Analysis.

Other Laryngeal Laryngeal Papillary Other
Surgery Type LPSCC, n Malignancies, n P Value Squamous Cell Laryngeal
Carcinoma Malignancies P Valuea
No surgery 189 34,794 .3030a
Local excision 114 10,831 Disease-specific
survival, %
Partial laryngectomy 15 2618 1y 97.1 87.9 \.0001
5y 83.1 64.5 \.0001
Total laryngectomy 10 7161 10 y 73.9 50.5 \.0001
Relative survival, %
Pharyngolaryngectomy 0 376 1y 95.5 86.0
5y 78.6 62.8
Laryngectomy, not 2 340 10 y 68.6 50.2
otherwise specified No surgery, n 119 23,681 .7718
Surgery of lymph nodes only 0 101 Surgery, n 115 22,045
No surgery 78.8 59.4 \.0001
Surgery, not 39 8333 disease-specific
otherwise specified survival, %
Unknown 1 601 Surgery disease-specific 87.4 70.0
survival, %
Radiation treatment a
Bolded values indicate significance.

None 107 16,465 .1499

Radiationb 258 46,368 .2713
Refused 0 485

Unknown 5 1837

a
P value compares surgery versus no surgery.
b
Includes beam, radioactive implants, radioisotopes, combination, and other
types.

enough reports to establish the characteristics of the lesion as

being locally contained with low risk of nodal or regional
spread. It has been established in the study of head and
neck SCC that the status of the lymph nodes in the neck is
the most important indicator of patient outcome.20 In
KSCC, lymph node metastasis at the time of diagnosis
occurs in 40% of cases.21,22 Distant metastases are usually
found in approximately 10% of cases. LPSCCs, on the
other hand, are early staged lesions, with T1 and stage 1
the most commonly described, occurring in 48.4% and
42.8% of cases, respectively. Nodal metastasis occurred in
only 16.3% of cases, and distant metastases were found in
just 1.3% of cases. These data demonstrate the less aggres-
sive nature of LPSCC compared with laryngeal KSCC.
This study validated other case series with respect to
increased survival of LPSCC compared with other laryngeal
malignancies. In this report 1-, 5-, and 10-year DSS was sig-
nificantly higher in LPSCC compared with other laryngeal
malignancies. The reported 5-year DSS of 83.1% in this
study is comparatively higher than the 60% reported in
prior studies for all other laryngeal malignancies.23 The
improved prognosis of PSCC compared with KSCC of the
Figure 1. Five-year disease-specific survival for laryngeal papillary
squamous cell carcinoma compared with other laryngeal malignan-
cies. P \.001 (log-rank).
larynx demonstrates the inherent differences in behavior
that this variant displays.2
Our study also demonstrated that high grade (stage III
and IV) had significantly lower 5-year DSS when compared
with low grade (stage I and II; 54.6% and 89.5%, respec-
tively; Figure 3). Because our sample size was fairly lim-
ited for cases with full staging and survival data (n = 11 for
high grade, n = 39 for low grade), these preliminary data
still warrant further research into the activity of both low-
and high-grade LPSCC.
This study demonstrated that patients who underwent
surgery had a higher DSS compared with those who did not,
in both LPSCC and other laryngeal malignancies (Table 5).
Unfortunately, we were unable to analyze the impact of
58
Figure 2. Five-year disease-specific survival for surgery versus no
surgery in laryngeal papillary squamous cell carcinoma. P = .1104
(log-rank).
Figure 3. Disease-specific survival for low-grade (stages I and II)
and high-grade (stages II and IV) laryngeal papillary squamous cell
carcinoma. Five-year disease-specific survival for low grade is
89.5% and for high grade is 54.6%.
chemotherapy in our cohort, as the SEER database does not
contain this information. Originally, surgical therapy was the
mainstay of treatment for laryngeal cancer. The treatment
algorithm changed in 1991, when the Department of
Veterans Affairs (VA) Laryngeal Cancer Study demonstrated
that chemotherapy and radiotherapy had similar survival rates
compared with surgery and radiotherapy.16 This finding was
supported by other large trials and validated with long-term
follow-up.17,24 However, in the past decade, there has been a
decline in overall survival in laryngeal cancer, which some
have attributed to the increased use of chemoradiation.23,25
Using the SEER database, we can assess a very interesting
trend in laryngeal cancer. The annual percentage change in
incidence for LPSCC does not demonstrate a statistically sig-
nificant change between 2000 and 2011. At the same time,
however, there is a relative decrease for all other laryngeal
cancers, a finding that reaches statistical significance. It is
possible that this trend can be a result of a gradual decrease
OtolaryngologyHead and Neck Surgery 153(1)
in smoking among the US population, therefore decreasing
the percentage of laryngeal malignancies. Is the increase in
HPV in the US population the catalyst to the increase in
LPSCC? Current and future research will answer this ques-
tion as we learn more pertaining to the molecular mechan-
isms underlying these neoplasms and which etiologic factors
are leading to neoplastic transformation.
The limitations of this study are mainly on the inherent
biases that are generated by database analysis. First, the
study period in which the data set was collected spans a
long period of time, from 1973 to 2011. There have been
important changes in diagnosis, treatment, and surveillance
of laryngeal cancers over this 40-year period. Second, data
concerning the HPV status of each patient were unavailable
to us in the SEER database. Third, because of inconsisten-
cies in reporting, most staging was unknown. Fourth, there
is a deficiency in clinical information with respect to spe-
cific surgical therapies, radiotherapy doses, use of che-
motherapy, as well as comorbidities. Last, the nature of data
input into the database across time and space leads to the
introduction of considerable heterogeneity.
Despite these limitations, the benefits of using a database
such as SEER are numerous. The standardization within the
database allows for uniform reporting of data across a wide
geography. This confers on this data set a greater external
validity by overcoming institutional and regional biases. In
addition, it is robust in number and generates better statisti-
cal power with which to draw conclusions, especially when
dealing with rare malignancies.
Conclusions
Laryngeal papillary squamous cell carcinoma is a distinct
entity compared with other laryngeal malignancies. These
tumors are locally invasive and only rarely display local and
distant metastasis. They have a higher DSS compared with
other laryngeal malignancies.
Author Contributions
Rahul Dutta, acquisition of data, analysis, drafting, final approval;
Qasim Husain, acquisition of data, analysis, drafting, final
approval; David Kam, acquisition of data, analysis, revision, final
approval; Pariket M. Dubal, acquisition of data, revision, final
approval; Soly Baredes, conception, revision, final approval; Jean
Anderson Eloy, conception, design, analysis and interpretation of
data, revision, final approval.
Disclosures
Competing interests: None.
Sponsorships: None.
Funding source: None
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