Human papillomavirus in the nasopharynx: A true entity?
The emergence of human papillomavirus (HPV) as a signifi-
cant contributor to the development of oropharyngeal carci-
noma has generated significant interest into patient
populations exposed to the virus and subsequent develop-
ment of oropharyngeal carcinoma. Due to the increased treat-
ment sensitivity and improved survival compared to non-
HPV tumors, the natural progression to investigate the
presence of HPV exposure in nonoropharyngeal sites is cru-
cial in personalizing treatment regimens to these patient
Previous reports have found that HPV has a tropism
toward lymphoepithelial-rich sites in the tonsil and base of
tongue; therefore, the nasopharynx is the most intriguing site
outside the oropharynx to study the prognostic impact of
HPV. Numerous single institution studies have reported on
the presence of HPV in nasopharyngeal carcinoma (NPC).
However, small patient cohorts (5-125 patients) with wide
range of HPV positivity (10%-80%) make conclusions on
such data difficult.
The largest multi-institution cohort of
patients with NPC with HPV data available found 13 of 125
patients (10%) harboring evidence of HPV.
ing publication by Dr Verma and his colleagues attempts to
overcome limitations in patient numbers by using the
National Cancer Database (NCDB) to study the prognostic
impact of HPV in NPC at a population level.
HPV-NPC at the hospital-registry level provides insight into
distribution of this disease to allow for increased awareness
and direct appropriate testing and treatment to affected
The NCDB is a nationwide, facility-based oncology data-
set that currently captures 70% of all newly diagnosed can-
cers in the United States annually reported from
approximately 1500 hospitals with Commission on Cancer-
accredited cancer programs.
Investigators are able to study
cancers that are relatively rare, such as NPC, and provide
information on sociodemographic, tumor, and treatment
details of these cancers. Follow-up data on patients allows
one to calculate overall survival as well. In 2010, the NCDB
provided a site-specific factor with HPV status included
making correlations with head and neck tumors and HPV
status possible. The authors of the accompanying publication
found that HPV-positivity in NPC does not provide a
clinically significant survival benefit compared with the
patients with HPV-negative NPC disease.
Presentation of HPV status using the NCDB has signifi-
cant limitations though, which Dr Verma et al illustrate in
their discussion. First, HPV status was only added to the
NCDB in 2010 and the implementation of such a variable
has lag time before being universally accepted across record-
ing facilities. As the variable is more widely recorded, the
presence of the new variable, in this case HPV, can be misin-
terpreted as increasing in incidence. Liederbach et al
lished on the incidence of HPV-oropharyngeal carcinoma
from 2010 to 2013 and found that the number of HPV-
oropharyngeal carcinoma cases increased over time and was
directly related to a decrease in the number of cases with
unknown HPV status. This result does not reflect a true
increase in incidence but is more representative of improved
data recording. Similarly, the increase in the number of
HPV-NPC diseases seen in Verma’s report likely reflects a
similar increase in HPV test recording and may not represent
a true increase in incidence.
In addition, an oral presentation at the 2017 North Amer-
ican Association of Central Cancer Registries meeting by
Kahl et al found that only 40% of patients with head and
neck cancer in the Surveillance, Epidemiology, and End
Results database reported any HPV testing being done from
2010-2013, of which only 4% of these patients had NPC.
A significant number of patients would have no HPV testing
reported, as evidenced by the Verma et al reporting 11,126/
12,389 (89.8%) of patients not having any HPV testing avail-
able. Drawing any valid conclusion becomes challenging in
Another limitation that may cause reporting error is that
the NCDB does not specify the method for how HPV status
was confirmed. Strategies toward HPV detection vary among
institutions based on available resources, tissue availability,
cost, and laboratory preferences.
The best test for HPV-
specific oropharyngeal carcinoma is identification of direct
E6/E7 mRNA transcripts within tissue samples.
ever, the technical demands and costs in testing specifically
for E6/E7 mRNA limits this assay to a small number of labo-
ratories. Consequently, many institutions use HPV in situ
hybridization when testing for HPV.
Using in situ
hybridization has the limitation of approximately 85%
Head & Neck. 2018;40:707–709. wileyonlinelibrary.com/journal/hed
2018 Wiley Periodicals, Inc.
Received: 19 October 2017
Accepted: 7 November 2017