HPV Acquires
Etiological Role in Head-and-Neck
Cancer
by David W. Sharp
Medicine Top Ten
Papers
Rank
Papers
Cites Mar-Apr
09
Rank
Jan-Feb
09
1
The ACCORD Study Group
(H.C. Gerstein, et
al.), "Effects of
intensive glucose
lowering in type 2
diabetes," New
Engl. J. Med.,
358(23): 2545-59, 12
June 2008. [Writing
Group: 10 U.S. and
Canadian institutions]
*311IJ
65
1
2
J. Yu, et al.,
"Induced pluripotent
stem cell lines
derived from human
somatic cells,"
Science,
318(5858): 1917-20, 21
December 2007. [Genome
Ctr. Wisconsin,
Madison; U. Wisconsin,
Madison] *243HE
63
2
3
The ADVANCE
Collaborative Group (A.
Patel, et
al.), "Intensive
blood glucose control
and vascular outcomes
in patients with type 2
diabetes," New
Engl. J. Med.,
358(24): 2560-72, 12
June 2008. [Writing
Group: 18 institutions
worldwide] *311IJ
52
6
4
S.E. Nissen, K. Wolski,
"Effect of
rosiglitazone on the
risk of myocardial
infarction and death
from cardiovascular
causes," New Engl.
J. Med., 356(24):
2457-71, 14 June 2007.
[Cleveland Clinic, OH]
*178DR
48
4
5
T.M. Frayling, et
al., "A common
variant in the
FTO gene is
associated with body
mass index and
predisposes to
childhood and adult
obesity,"
Science,
316(5826): 889-94, 11
May 2007. [19
institutions worldwide]
*166HM
46
5
6
L.J. Scott, et
al., "A
genome-wide association
study of type 2
diabetes in Finns
detects multiple
susceptibility
variants,"
Science,
316(5829): 1341-5, 1
June 2007. [12 U.S. and
Finland institutions]
*173PS
42
3
7
E. Zeggini, et
al., "Replication
of genome-wide
association signals in
UK samples reveals risk
loci for type 2
diabetes,"
Science,
316(5829): 1336-41, 1
June 2007. [10 U.K.
institutions] *173PS
41
7
8
R.R. Holman, et
al., "10-year
follow-up of intensive
glucose control in type
2 diabetes," New
Engl. J. Med.,
359(15): 1577-89, 9
October 2008. [6 U.K.
institutions] *358FS
41
†
9
G. Hudes, et
al.,
"Temsirolimus,
interferon alpha, or
both for advanced
renal-cell carcinoma,"
New Engl. J.
Med., 356(22):
2271-81, 31 May 2007.
[17 institutions
worldwide] *172PO
37
8
10
K. Miller, et
al., "Paclitaxel
plus bevacizumab versus
paclitaxel alone for
metastatic
breast
cancer,"
New Engl. J.
Med., 357(26):
2666-76, 27
December 2007. [9
U.S. and Canadian
institutions]
*245UO
His work on sexually transmitted
human
papilloma virus (HPV) and cancer of the cervix won for
Prof. Harald zür Hausen (Deutsches
Krebsforschungszentrum, Heidelberg, Germany) a share in the
2008 Nobel Prize for medicine. The prevailing notion when
this research began in the 1970s had been that herpes
simplex virus was a probable cause. As with the late F.
Peyton Rous (viral transmissibility of a sarcoma in
chickens demonstrated 1911, Nobel Prize 1966) recognition
took a while. Today, we have two licensed vaccines against
oncogenic HPV so, on paper at least, cancer of the cervix
can now be seen as a potentially preventable disease,
subject to the resolution of issues such as the duration of
the conferred protection and the role of oncogenic HPV
types other than the two in the current vaccines (D.M.
Harper, Lancet, 373[9679]: 1921-2, 2009; G.F.
Sawaya, K. Smith-McCune, New Engl. J. Med.,
356[19]: 1991-3, 2007).
Electron micrograph of
human papillomavirus (HPV).
Courtesy of NCI. 1986.
There are at least 100 types of HPV. Not all are oncogenic.
Most cervical cancers are associated with types 16 and 18,
and this association is strong. Might there be other
cancers for which HPV has a role in causation? The evidence
would come from epidemiology and molecular virology, and
there are several candidates—other gynecological
cancers, esophageal cancer, and cancers of the head and
neck, for example.
A decade ago HPV, in contrast to tobacco and alcohol, would
not have been prominent in a list of known or possible risk
factors for head-and-neck cancer. That has changed. The
past 12 months have seen publication of a couple of dozen
review articles covering HPV and this cancer specifically
(e.g., A. Argiris, et al., Lancet,
371[9625]: 1695-709, 2008) or the virus and cancers more
generally, including one by Prof. zür Hausen himself
(Virology, 384[2]:260-5, 2009). A research paper
that will have been influencing this new thinking is now at
#15 (G. D’Souza, et al., New Engl. J.
Med., 356[19]: 1944-56, 2007; total cites 139, latest
count 33).
When Dr. Gypsyamber D’Souza and her colleagues began
their case-control study (#15), the molecular case for the
involvement of oncogenic HPV in squamous cell carcinomas
(SCC) of the head and neck, and especially for those in the
oropharynx, was stronger than the epidemiological. One
hundred cases of oropharyngeal cancer and 200 cancer-free
controls completed self-administered questionnaires
exploring demographics, personal and family medical
histories, oral hygiene, tobacco and alcohol use, and
sexual behavior. They also underwent oral mucosa sampling
for HPV DNA studies. The main finding was that "Oral HPV
infection is strongly associated with oropharyngeal cancer"
whether or not the risk factors of tobacco and alcohol were
present. Furthermore, and confirming earlier suggestions,
there were significant associations with certain sexual
behaviors—e.g., numbers of vaginal and oral sex
partners and casual partners—after adjustment for
factors such as alcohol and tobacco.
D’Souza et al. speculate that there may be
two different pathways in the development of this cancer,
one driven by tobacco and/or alcohol and the other by HPV.
We cannot yet say for certain that oral HPV infections in
this context are acquired via oral-genital contact. The May
10, 2007 New England Journal of Medicine (something of an
HPV special issue, with no fewer than eight items on this
virus) carries an editorial on #15 by Dr. Stina
Syrjänen (University of Turku, Finland). In a Finnish
study, where participants were recruited via a maternity
unit, there was no association between oral sex and oral
HPV infection (M.Rintala, et al., J. Clin.
Virol., 35[1]: 89-94, 2006), and later work from
D’Souza and colleagues confirms that simple kissing
should not be ignored in this discussion (G. D’Souza,
et al., J. Infect. Dis., 199[9]: 1263-9,
2009; see also editorial comment by A.R. Kreimer, pp.
1253-4).
Despite concerns that HPV-associated head-and-neck cancer
may be on the increase—and a recent Swedish paper
speaks of an "epidemic...with soon practically all
tonsillar SCC being HPV positive, as in cervical cancer"
(A. Näsman, et al., Int. J. Cancer,
125[2]: 362-6, 2009)—it is also too soon to say that
the HPV vaccination program should be extended to try and
deal with cancers of the oropharynx, but if that did happen
the focus would no longer be on girls only.
Meanwhile, fuel for the debate on the management of type 2
diabetes (Science Watch, 20[3]: 5,
May/June 2009) continues to accumulate. The United
Kingdom Prospective Diabetes Study (UKPDS) began as a
randomized trial of intensive glucose control versus
management by diet. The trial interventions stopped 12
years ago, and 10 years of follow-up in the post-trial
phase (equating to 66,000 patient-years) are reported in
#8. The benefits recorded earlier were sustained after the
trial participants left the randomized phase, and
significantly reduced risks of myocardial infarction and
death from any cause emerged for those who had been on
sulfonylurea or insulin. However, this "legacy effect" was
not seen for the subgroup of UKPDS patients randomized to
intensive blood-pressure control (R.R. Holman, et
al., New Engl. J. Med., 359[15]: 1565-76,
2008).
A former deputy editor of The Lancet, Mr.
David W. Sharp, M.A. (Cambridge) is a freelance writer
living in Minchinhampton, U.K.
KEYWORDS: HUMAN PAPILLOMAVIRUS, HPV, HEAD AND NECK CANCER,
OROPHARYNGEAL CANCER, GYPSYAMBER D’SOUZA, STINA
SYRANEN.