Oropharyngeal carcinoma related to human papillomavirus
BMJ 2010; 340 doi: https://doi.org/10.1136/bmj.c1439 (Published 26 March 2010) Cite this as: BMJ 2010;340:c1439All rapid responses
Rapid responses are electronic comments to the editor. They enable our users to debate issues raised in articles published on bmj.com. A rapid response is first posted online. If you need the URL (web address) of an individual response, simply click on the response headline and copy the URL from the browser window. A proportion of responses will, after editing, be published online and in the print journal as letters, which are indexed in PubMed. Rapid responses are not indexed in PubMed and they are not journal articles. The BMJ reserves the right to remove responses which are being wilfully misrepresented as published articles or when it is brought to our attention that a response spreads misinformation.
From March 2022, the word limit for rapid responses will be 600 words not including references and author details. We will no longer post responses that exceed this limit.
The word limit for letters selected from posted responses remains 300 words.
In response to Mehanna and colleagues who identified the need for
data on
the incidence of HPV-related oropharyngeal cancer from Asia, we report
that
Australian data support the changing epidemiology of oropharyngeal cancer
observed in other western countries. Our study of 302 oropharyngeal
cancers
from Sydney Hospitals showed that the incidence of HPV positive (HPV DNA-
positive/p16-positive) oropharyngeal squamous cell cancer increased from
19% in 1987-1990 to 47% in 2001-2005 and to 60% in 2005-2006
(doi:10.1016/j.vaccine.2010.02.098). Based on Australian cancer incidence
data, we estimated that on average 1.56 cases of oropharyngeal squamous
cell cancer per 100,000 males per year were induced by HPV types targeted
by the HPV vaccines over the period 2001-2005. In Australia the
quadrivalent
HPV vaccine has been used in the school-based, government-funded
program for girls 12 to 13 years of age and a two-year catch up program
for
women up to 26 years. The quadrivalent HPV vaccine has been approved for
boys but is not subsidized by the government. Our data inform the debate
on
the merits of extending our vaccination program to boys.
We concur with the authors that it is premature to base treatment on
the HPV
status of tumours pending results of randomised trials designed to
establish
whether less intensive treatment is justified in patients with HPV-
positive
oropharyngeal cancer. Recent data suggest that any modification of
treatment strategies based on HPV status may also need to take account of
the effect of smoking in negating the beneficial effect of HPV on outcome.
Competing interests:
AH and GH hold shares
(predating the availability of
HPV vaccine). AG and SG have
professional associations with
CSL; and SG also with
GlaxoSmith Kline (all unrelated
to this study).
Competing interests: No competing interests
In a recently published article (1), Mehanna et al. described
increasing incidences of oropharyngeal squamous cell carcinomas worldwide
and the involvement of human papillomavirus (HPV) type 16 in oral cancers.
We also found the similar trend of HPV in the etiology of ameloblastoma in
Indian population (2).
Oral cancers ranks eighth in the worldwide and number of cases are
increasing constantly in developing countries, including India (3). Based
on World Health Organization classifications, 1992, a retrospective study,
conducted in India from 1971 - 2006 demonstrated, out of 250-odontogenic
tumor cases, 61.5% cases were due to ameloblastoma (4), which may be an
alarming feature of HPV cases in India. Ameloblastomas are enigmatic group
of true, benign, epithelial tumors of odontogenic origin, which do not
undergo differentiation to the point of enamel formation.
Revelations concerning role of HPV in oral carcinogenesis have
prompted us to ensure whether the virus plays a similar role in the
etiology of ameloblastoma, in India. Our results indicated that the
presence of HPV in all the samples (n=20) and 95% of samples were positive
for HPV type 16. The subjects taken for the study were from both urban and
rural population. The age of the patients ranged from 13 to 67 years
(average age of 27.5 ± 16.05 years) with male to female ratio was 1:0.43.
Average age for male patients was 26.6 ± 14.07 years and for female
patients it was 29.6 ± 20.22 years (2).
A few studies showed that the HPV might be having a role in the
ameloblastoma (5). But none of the studies shown convincing evidences for
the integration of the viral DNA into the tumor cells. Relation between
the oral cancers and ameloblastoma still remains unclear due to the
complex interplay of human behavioral viral and host factors, which are
not clear. To our knowledge, this is the first report, providing evidence
for the role of HPV in the etiology of ameloblastoma in Indian population.
Considering the seriousness of the inconclusive diagnosis of the
etiology of ameloblastoma in Indian population, there is an urgent need
for the proper diagnosis of HPV in ameloblastomas in the developing
countries. Conclusively, the high incidence of HPV-associated
ameloblastomas in men suggests that vaccination of all young people
(irrespective of gender) against HPV may be considered, as well as
ameloblastoma HPV status may strongly help in therapeutic choice, response
and survival.
References:
1. Mehanna H, Jones TM, Gregoire V, Ang KK. Oropharyngeal carcinoma
related to human papillomavirus. BMJ. 2010; 340:c1439. doi:
10.1136/bmj.c1439.
2. Saxena SK et al., (unpublished data) 2010.
3. Petersen PE. The World Oral Health Report 2003: continuous
improvement of oral health in the 21st century--the approach of the WHO
Global Oral Health Programme. Community Dent Oral Epidemiol. 2003; 31
Suppl 1: 3-23.
4. Sriram G, Shetty RP. Odontogenic tumors: a study of 250 cases in
an Indian teaching hospital. Oral Surg Oral Med Oral Pathol Oral Radiol
Endod. 2008; 105(6): e14-21.
5. Namin AK, Azad TM, Eslami B, Sarkarat F, Shahrokhi M, Kashanian F.
A study of the relationship between ameloblastoma and human papilloma
virus. J Oral Maxillofac Surg. 2003; 61(4): 467-70.
Competing interests:
None declared
Competing interests: No competing interests
Hisham Mehanna and colleagues have highlighted the increasing
incidence of oral and oropharyngeal cancer in the UK and its likely
association with sexually transmitted Human Papilloma Virus (HPV).
However by reporting oropharyngeal cancer along with oral cancer the true
rate of increase of oropharyngeal cancer is probably being masked.
Using data from the Scottish Cancer Registry we have found that
oropharyngeal cancer now has the greatest rate of increase of any cancer
in Scotland.
As can be seen from figure 1 it has overtaken both melanoma of the
skin and adenocarcinoma of the oesophagus. In contrast the incidence of
invasive cancer of the cervix is decreasing. Simply using linear
regression to fit a line to age standardised rates between 1987 and 2006
yields an estimated 2.9 fold increase of oropharyngeal cancer in males,
and a 2.4 fold increase in females. When looking at Scottish Cancer
Registry data we grouped Base of Tongue (C01), Palate (C05), Tonsil (C09)
and Oropharynx (C010). These codes were selected because they relate to
the anatomically defined sub sites of the oropharynx enabling analysis of
all registered cases. There was an increase in incidence of each site
within the oropharynx but the greatest was for tonsil and base of tongue.
HPV-associated oropharyngeal cancer appears to have a better
prognosis than non-HPV-related oropharyngeal cancer. Population-based data
from the South East of Scotland showed a 34% difference in 5-year survival
in favour of females in a cohort diagnosed during 1999-2001, but there was
no such difference in survival between males and females in a cohort from
2003-2005. Despite 70% of patients presenting with stage IV disease, the 5
-year survival for males in SE Scotland is now 68%. It is as yet unknown
if this change in survival relates to HPV status. However with increasing
numbers of younger patients surviving, the morbidity from treatment for
individuals and the health care burden to the NHS will be significant.
Perhaps vaccination for boys should be re-evaluated.
Competing interests:
None declared
Competing interests: No competing interests
My thanks go to the editorial team of the BMJ for publishing the article by
Hisham Mehanna and colleagues. There has evidently been an increase in risk
associated with orogenital sexual intercourse in many areas across the world,
including Australia. The associated increase in oropharyngeal cancer in a
younger population who do not have the normal risk factors for Upper
Aerodigestive Tract Squamous Cell Cancer has been noted by clinicians for
the last 2 decades or more. We face an increasing number of younger patients
with this disease. Perhaps fortunately, current modes of treatment appear to
be effective in curing the cancer, but at great cost of lifelong morbidity. The
personal toll of chronic ill health and reduction in financial contribution to
society bring attendant increase in cost, physical, psychological and
monetary.
We do have an effective vaccine for the HPV subtypes associated with this
cancer, and potentially could see eradication of this aetiologic agent and
subsequent reduction in disease toll on life and health.
Current cost effectiveness of vaccination in terms of lives saved from
reduction in oropharyngeal cancer incidence has been based on old data. If
we progress to more than 90% of oropharyngeal cancers being associated
with HPV, as the Stockholm group has already seen, and factor in the rising
incidence in a younger population, it is quite likely that we will get closer to
what ever figure politicians have in mind when valuing a human life.
I strongly support the roll out of free vaccination to all members of the
population a risk of infection. In addition, primary health carers and medical
educationalists should be aware that orogenital sex has a significant health
impact, and that this message should form part of all sex education to young
people.
Competing interests:
None declared
Competing interests: No competing interests
I was surprised to read that oesophageal squamous cell carcinoma
would occur in the middle throat. Is this a mis-print? Perhaps it should
be 'oropharyngeal?'
Competing interests:
None declared
Competing interests: No competing interests
Re: Oropharyngeal carcinoma related to human papillomavirus
Dear Editors,
HPV infections are also associated with breast cancers. [references below]
References
http://www.ncbi.nlm.nih.gov/pubmed/19851859
http://www.ncbi.nlm.nih.gov/pubmed/19773762
http://www.ncbi.nlm.nih.gov/pubmed/19724278
http://www.ncbi.nlm.nih.gov/pubmed/18936692
http://www.ncbi.nlm.nih.gov/pubmed/18427947
http://www.ncbi.nlm.nih.gov/pubmed/16865407
http://www.ncbi.nlm.nih.gov/pubmed/23183846
http://www.ncbi.nlm.nih.gov/pubmed/23011481
http://www.ncbi.nlm.nih.gov/pubmed/22566779
http://www.ncbi.nlm.nih.gov/pubmed/22214962
http://www.ncbi.nlm.nih.gov/pubmed/22012724
http://www.ncbi.nlm.nih.gov/pubmed/18648363
http://www.ncbi.nlm.nih.gov/pubmed/18413729
http://www.ncbi.nlm.nih.gov/pubmed/17310842
http://www.ncbi.nlm.nih.gov/pubmed/16780823
http://www.ncbi.nlm.nih.gov/pubmed/16222323
http://www.ncbi.nlm.nih.gov/pubmed/15642157
http://www.ncbi.nlm.nih.gov/pubmed/15494272
Competing interests: No competing interests