TITLE: The Human Papillomavirus Vaccine an=
d its
Implications in Otolaryngology
SOURCE: Grand Rounds Presentation, University of Texas Medical Branch,
Department of Otolaryngology
DATE: Sept 30, 2010
MEDICAL STUDENT: Kathryn Wheat, MSIV
FACULTY PHYSICIANS: Susan D. McCammon, MD and Harold S. Pine, MD
DISCUSSANT: Susan D. McCammon, MD
DISCUSSANT: Vicente A. Resto, MD, PhD
DISCUSSANT: Harold S. Pine, MD
SERIES EDITOR: Francis B. Quinn, Jr., MD
ARCHIVIST: Melinda Stoner Quinn, MSICS
"=
This
material was prepared by resident physicians in partial fulfillment of
educational requirements established for the Postgraduate Training Program =
of
the UTMB Department of Otolaryngology/Head and Neck Surgery and was not
intended for clinical use in its present form. It was prepared for the purp=
ose
of stimulating group discussion in a conference setting. No warrantie, eith=
er
express or implied, are made with respect to its accuracy, completeness, or
timeliness. The material does not necessarily reflect the current or past
opinions of members of the UTMB faculty and should not be used for purposes=
of
diagnosis or treatment without consulting appropriate literature sources and
informed professional opinion."
INTRODUCTION
In =
the
United States, squamous cell carcinoma of the head and neck comprises about=
4%
of all malignancies. This corresponds to an estimated 17 per 100,000 persons
with newly diagnosed squamous cell carcinoma of the head and neck per year.=
During 1998–2003, the incidence rate of Human Papillomavirus (HPV)-as=
sociated
cancers in the United States was 10.6 per 100,000 people. While cancers of =
the
oropharynx, oral cavity, and larynx are attributable to tobacco and alcohol use twice as often =
as
HPV association, there is still an average of 7360 cases of potentially
HPV-associated cancers in the head and neck region occurring annually in the
US, causing significant morbidity and mortality. These cancers, which
predominate in men, are second only to cervical cancer in the number of
HPV-associated cancers in the United States, and the majority of cases are
attributable to HPV16 and 18 infections. Additionally, though rare, recurre=
nt
respiratory papillomatosis (RRP) is a condition caused by HPV6 and 11 and a
source of major morbidity, especially in children. This condition, as well =
as
cancers of the head and neck, requires monitoring and future studies of the
successful prevention of such conditions with the advent of the HPV vaccine=
.
Com= bined with avoidance of tobacco and alcohol use, reducing the risk of HPV infecti= on through vaccination and sexual risk reduction could potentially prevent thousands of cases of head and neck cancer, as well as recurrent respiratory papillomatosis, and the associated morbidity and mortality of these disease= s. However, for such vaccination recommendations to take place, studies must be conducted examining the pathology and activity of HPV infection in these anatomical regions and the relationship to oncogenesis, as co-infection wit= hout oncogenesis can also occur. Further, incidence of these cancers after HPV vaccine administration in the US should be studied, and if possible, trials should be undertaken as in the studies for approval for cervical cancer prevention. Lastly, vaccine recommendation may require cost-effectiveness studies for approval for state funding, and this funding may need to be extended to boys as well as girls, and possibly to adults.
The= goal of this paper is to give background information on the main HPV-associated head and neck pathologies, drawing from findings of the Assessment of the Burden= of HPV-Associated Cancers in the United States (ABHACUS) study, as well as oth= er research articles and reviews. Additionally, it will discuss the need to project research requirements and public health and policy considerations s= uch as socioeconomic distribution, age to vaccinate, and state funding for appr= oval of and use of the HPV vaccine for conditions relevant to the field of Otolaryngology.
INCIDENCE
AND EPIDEMIOLOGY
Oral Cavity and Oropharyngeal
Cancer
According to Surveillance, Epidemiology, and End
Results (SEER) Cancer Statistics Review of the National Cancer Institute, i=
t is
estimated that around 35,000 cases of oropharyngeal cancer will be diagnose=
d in
2010, with an age-adjusted incidence of 10.4 cases per 100,000 persons.
Squamous cell carcinoma of this region is about 3-4 times more common in men
than women and most often develops in or after the fifth decade of life.
According to a study by Ryerson, et al on patient data from 1998–2003, out =
of
this total number, 44,160
cases of potentially HPV-associated cancers of the oropharynx and oral cavi=
ty
were identified, including 19,239 (43.6%) tonsillar, 16,964 (38.4%) base of
tongue, and 7957 (18.0%) =
other[*] oropharyngeal tumors. Over the=
time
period, 35.6% cases of oropharyngeal cancers are HPV+ (87% of these with HP=
V16)
and 23.5% cases of oral cancers are HPV+ (68% of these with HPV16).
The incidence rates for these sites were highest= among blacks, and higher among non-Hispanics and men than among Hispanics and wom= en. The annual incidence rates of potentially HPV-associated cancers of the ton= sil and base of tongue both increased significantly from 1998 through 2003 while the incidence of head and neck squamous cell carcinoma at other sites decli= ned. Also, it has been suggested in several studies that increases in rates of cancer in certain sites of the oropharynx, despite the reduction in tobacco exposure among Americans over recent decades, could be attributable to HPV infections, with some studies pointing to causes such as particular sexual behavior characteristics.
For example, an analy= sis of eight multinational observational studies that compared 5642 cases of head = and neck cancer with 6069 controls found that the risk of developing oropharyng= eal carcinoma was associated with a history of six or more lifetime sexual partners, four or more lifetime oral sex partners, and an earlier age at fi= rst sexual intercourse in men. The implications of this are discussed further l= ater in this paper. However, cancers of the oropharynx found to be associated wi= th HPV have been shown to have a more favorable prognosis than non-HPV related oropharyngeal carcinoma, particularly in non-smokers.
Laryngeal Carcinoma
According to SEER, an estimated 12,720 men and w= omen will be diagnosed with cancer of the larynx in 2010, with an age-adjusted incidence of 3.4 per 100,000 persons. Laryngeal carcinoma is more common in African American than in whites, with a ratio of 3.5:1, and more common in males than females, with a ratio of 5:1. In the 1950s, this ratio was 15:1,= but has since decreased, likely due to the greater number of females using toba= cco. Laryngeal carcinoma most often affects middle-aged or older men, with a peak incidence between 50 and 60 years.
As mentioned above, the greatest risk factor for= the development of laryngeal cancer is tobacco use, the risk of which can decre= ase after smoking cessation. Alcohol use creates a synergistic effect, but it is unknown whether alcohol is an independent risk factor. HPV is among other causes investigated in laryngeal cancer development and researchers in sepa= rate studies have identified HPV DNA in a range of 3.3-50% of biopsies of laryng= eal carcinoma. In a meta-analysis of studies completed on the presence of HPV in non-cervical cancer biopsy samples, Mammas, et al found two studies with <20%, four studies with 20-40% and 3 studies with >40% detection rate= s of HPV through polymerase chain reaction (PCR).
Recurrent Respiratory Papillomatosis
In the United States, between 1500 and 2500 new = cases of childhood-onset recurrent respiratory papillomatosis (RRP) are estimated= to occur every year, making the incidence among children around 4.3 cases per 100,000 persons. Adult incidence is lower, at 1.8 cases per 100,000 persons. RRP has a bimodal distribution, with a peak in childhood years around two to three years old, and a second peak at age 20 to 40 years old. The male-to-female ratio in children is equal, but in adults the male-to-female ratio may be as high as 4:1. Most children with RRP appear to be the first-= born of young mothers and come from families with low economic status.
RRP is more common in children, and is also more aggressive, requiring multiple surgical procedures, averaging 15 in the chi= ld’s lifetime. Childhood-onset RRP presents with hoarseness and stridor, is often mistaken for asthma or chronic bronchitis, and can lead to complete airway obstruction. While RRP is considered a rare disease with variable clinical caliber, the number of surgeries performed each year can add up to around 1= 5,000, costing an estimated $100 million.
While many studies have shown a connection betwe= en exposure of the upper aerodigestive tract of a child to a mother with an HPV infection during vaginal delivery, there have been numerous children born to mothers with active HPV infection that have not acquired RRP. On the other hand, studies have suggested that HPV can be detected in up to 20% of disease-free mucosa in the anogenital area of pregnant women. However, there has also been a report of a child born by cesarean section who later develo= ped RRP. Regardless of the mode of transmission, because RRP is know to be caus= ed by HPV6 and 11, it will become important to control the burden of this dise= ase by controlling HPV infections, whether through vaccination of mothers, and/= or through childhood vaccinations at an early enough age to prevent occurrence= .
CERVICAL CANCER BACKGROUND
Therefore, a pertinent question is, how would th= e HPV vaccine acquire approval for use to prevent cancers that are believed to be associated with HPV? What kind of evidence is needed? To understand this, a brief history of the research and vaccine approval for use to prevent cervi= cal cancer is needed.
Cervical cancer research has been ongoing since = the mid 1990s and it was not until the early 2000s that vaccine trials began. A= fter the beginning phase trials, a benchmark study was completed by the Females United to Unilaterally Reduce Endo/Ectocervical Disease (FUTURE) II Study G= roup in 2006. They published their findings and suggestions in the New England Journal of Medicine in= 2007, where it was explained that their phase 3 trial of the quadrivalent HPV vac= cine (covering HPV6, 11, 16, 18) had an efficacy of 98% of preventing high-grade cervical intraepithelial neoplasia. This study was conducted using 12,167 females (5,305 in the vaccine group and 5,260 in the placebo group) between= the ages of 15 and 26 years over a three-year period.
Both the quadrivalent and bivalent vaccine (cove= ring HPV16 and 18) have been developed and approved by the Food and Drug Adminis= tration (FDA) for females aged nine through 26 years to prevent cervical cancer (HP= V16 and 18) and genital warts (HPV6 and 11). While each vaccine uses a different adjuvant[†], the concept is the same-- virus-like particles (VLPs) are formed from the L1 protein of the outer surface of the virus, acting as antigens to which the = body can form antibodies to fight off and prevent future infections of these particular strains of HPV.
Because of the findings from the vaccine studies= , the Advisory Committee on Immunization Practices (ACIP) of the CDC recommends routine three-dose intramuscular vaccination of females aged 11 or 12 years using either the bivalent or quadrivalent vaccine. It can be started at age nine years and is currently recommended for all females between ages 13 and= 26 years who have not been previously immunized or who have not completed the three-= dose series. These ages are targeted because the ideal time to give the vaccine = is before possible contact with HPV, which is most commonly acquired through sexual contact.
As of May 2010, the FDA approved the use of the = quadrivalent vaccine in males aged nine through 26 years to reduce their likelihood of acquiring genital warts. However, mathematical models suggested that adding male vaccination was not the most cost-effective strategy when >80% of females were being vaccinated, and that improving coverage in females would= be a better use of public health resources. Nonetheless, it is approved for us= e in males, and as with females, is most effective when given before exposure to= HPV through sexual contact.
ASSESSING THE BURDEN OF HPV-ASSOCIATED CANCERS IN THE UN=
ITED
STATES (ABHACUS)
In 2008, the Centers for Disease Control (CDC) published a supplement in the November edition of Cancer entitled “Assessing the Burden of HPV-Associated Cancers= in the United States” (ABHACUS). This supplement was comprised of 18 articles = and data from two cancer registries (the CDC National Program of Cancer Registr= ies [NPRC] and the National Cancer Institute (NCI) Surveillance, Epidemiology a= nd End Results [SEER]) to establish a baseline of HPV disease burden at the ad= vent of the use of the HPV vaccine. The= goals as outlined by ABHACUS are to monitor:
·
Ag=
e-specific
rates of HPV-associated cancers
·
Ag=
e-specific
rates of HPV-associated cancer precursors
· =
Di=
stribution
of associated HPV types in cancers and cancer precursors
·&nb=
sp;
Incidence of carcinoma precur=
sors
and invasive carcinoma along with prevalence of vaccination, and
·&nb=
sp;
Methods of linking screening =
and
risk factor data that are already being collected by other surveillance dat=
a.
ABHACUS not only initiated the monitoring of the impact of the vaccine on cervical pre-cancers and cancer, but also the impa= ct of the vaccine on non-cervical HPV-associated cancers, as well as some of their associated precancerous lesions. A continued effort will require funding an= d an organized national effort led by experts. Baseline incidence of HPV-associa= ted cancers were the following:
· 10,800 HPV-associated cervical cancers
occurred per year.
· Nearly 7,400 potentially HPV-associated
cancers of the oral cavity and oropharynx occurred per year with a
male-to-female ratio of 3.3:1.
· More than 3,000 HPV-associated anal can=
cers
occurred per year.
· About 2,300 new cases of vulvar cancer =
occurred
each year.
· Penile cancer was relatively rare, stri=
king
about 800 men each year.
· About 600 women per year developed vagi=
nal
cancers.
As shown above, oral cavity and oropharyngeal ca= ncers represent the second-most HPV-affected site, drawing attention to the poten= tial that widespread HPV vaccine use could have on decreasing the number of case= s in the United States. However, as ABHACUS and other studies have suggested, HPV presence, activity, and oncogenic potential are different entities, and the mere amplification by PCR of tissue samples does not necessarily equate with HPV as the cause of cancer. Further, the use of the term “HPV-associated” signifies that the researchers of ABHACUS chose these different locations of cancers because of their documented propensity to be sites of cancer direct= ly caused by HPV, but all the cases noted in the SEER and NPRC registries are = not caused by HPV. It is still important to continue these studies, as research= to validate the role of HPV in cervical cancer were ongoing for almost two dec= ades before the vaccine was developed and approved. On a similar note, in the ca= se of RRP (not investigated in ABHACUS), one study concluded that HPV DNA is present in 2% of tonsillectomy patients, whereas the incidence of RRP is on= ly 0.004%, suggesting more than infection is needed to cause RRP, namely, host factors such as increased susceptibility to HPV infection.
Relation to Socioeconomic Status
In order to better understand target populations= and reduce disparities in the distribution of information and resources, ABHACUS also investigated demographic characteristics of the HPV-associated cancers. With regard to oral cavity and oropharyngeal cancer there was an increased incidence with higher education, low-level to mid-level income, and residen= ce in metropolitan or suburban areas. Ten to twenty percent poverty status was associated with decreased oral cavity and oropharyngeal cancer rates.
In females, Hispanic ethnicity, Asian/Pacific Is= lander race, and rural residence were associated with lower rates of oral cavity a= nd oropharyngeal cancer. In counties with high school education rates of 75% to <85%, there was a lower incidence rate than those with 85% high school education. As mentioned above, current smoking was associated with increased incidence rates of oral cavity and oropharyngeal cancer.
In males, Hispanics and those residing in a coun= ty with <85% high school education had decreased rates of oral cavity and oropharyngeal cancer. Higher smoking prevalence and residence in a county w= ith lower median household income were also associated with increased incidence rates.
Concerning ethnicity and rural-urban status, Asian/Pacific Islanders had significantly higher incidence rates in rural a= reas while for whites, the adjusted incidence rate was lower in rural counties compared with metropolitan areas. Overall, blacks had significantly higher incidence rates compared with whites in metropolitan as well as rural areas. Asian/Pacific Islanders had a decreased incidence rate compared with whites= in metropolitan areas.
While the ABHACUS study covers >76% of the Un= ited States population, consistent data collection through the cancer registries must be continued to monitor changes in HPV-associated cancers. Once again, demographics are important in determining allocation of resources and will = be discussed further in the policy section.
Years of Potential Life Lost (YPLL) and
Productivity Costs
ABHACUS conducted studies to estimate the burden= of HPV-associated cancers in terms of years of potential life lost and productivity costs. These values encompass all cervical, anal, vaginal, vul= var, and penile cancers and a subset of oral cavity and oropharyngeal cancers. Of note is the fact that values are derived from the total numbers of cancers = in each of these areas, without taking the percentages of each of these cancers that could be attributed to HPV.
In summary, cancer-specific estimates ranged fro= m 3654 YPLL each year for penile cancer to 45,815 YPLL for oral cavity and oropharyngeal cancer in men and from 5199 YPLL for vaginal cancer to 89,936 YPLL for cervical cancer in women. In women, oral cavity and oropharyngeal HPV-associated cancers caused 17,773 YPLL each year. Oral cavity and oropharyngeal cancer mortality costs were calculated using 2003 data on US mortality, life tables, annual earnings, household services, and labor force participation rate. Among men, oral cavity and oropharyngeal cancer had the highest estimated cost at $1.1 billion ($463,623 per death). Among women, cervical cancer had the highest estimated cost at $1.8 billion ($541,576 per death). In women, oral cavity and oropharyngeal HPV-associated cancers cost $270 million.
Concerning ethnic distribution, in white non-Hispanics, the highest mortality costs were cervical cancer accounting = for 44.2% of the total, oral cavity and oropharyngeal accounting for 40.9%, and anal cancer accounting for 5.8%. The ABHACUS report quantified burdens by race/ethnicity, which, as mentioned above, can be used to assess relative versus overall burdens of cancer, which then can help inform decisions about the location of and audience for cancer prevention programs and services. T= he drawbacks of this study, however, were that information on race-specific earnings was not incorporated, possibly causing an under- or over-estimatio= n of productivity losses; pain, suffering, and psychosocial costs were not accou= nted for; society’s value on an individual cannot be calculated; estimates apply= to HPV-associated cancers and not necessarily the percentage specifically caus= ed by HPV; and direct and indirect medical costs, as well as caregiver costs, = were excluded from the analysis.
Studies on economic burden of a disease and cost-effectiveness of prevention and treatment are generally important in deciding the approach(es) taken against certain diseases and are used in the formulation of healthcare policy. As noted in the ABHACUS study, HPV is pre= sent in oral cavity and oropharyngeal cancers, second only to its presence in cervical cancer. Socioeconomic parameters have been researched and the econ= omic burden is apparent. As incidence studies continue following the use of the = HPV vaccine, and as more studies on the pathophysiology of HPV-associated cancer continues, the evidence most likely will grow, underscoring the need for HPV vaccination, cancer screening, and other effective early detection programs= for HPV-associated cancers.
PUBLIC
POLICY AND PUBLIC HEALTH
Given the studies and evidence above, it would s= eem that the United States is on its way to noticing the potential benefits of = the HPV vaccine beyond preventing cervical cancer. However, several questions n= eed to be addressed before the vaccine is not only recommended by the CDC, but = also before states will fund distribution and coverage of the vaccine as well as mandate education about its scope of beneficial effects. The vaccine would = have to be proven as cost-effective in boys as well as girls, and the decision w= ould have to be made whether or not to mandate coverage for entrance into school= s. The question remains unanswered as to how many years surveillance of HPV-related cancers will have to continue before a significant effect on incidence rates is seen, if any.
With recurrent respiratory papillomatosis, sever= al different questions are asked. Because it is a less common disease, in what manner and how long should incidence be tracked? Should studies be construc= ted to look at mothers who received the vaccine and the incidence of RRP in the= ir children compared to unvaccinated mothers? It would also be difficult to do= any prospective analysis for vaccination for this disease, as it would involve either infants at birth or two months, as RRP has been shown to begin in the first weeks of life, though often not symptomatic until six months at the earliest. If long-term studies of HPV-vaccinated mothers show no change in = the incidence of RRP in children, a study such as this may need to be undertake= n, in a fashion similar to other vaccines that have been approved for administration at birth or two months (Hepatitis B, DTap, Hib, PCV, IPV, Rotavirus.) Further, another facet that would need to be investigated is the cost-effectiveness of the vaccine, and the disease burden that would be relieved through its determined efficacy.
An additional important factor will be determini= ng the socioeconomic characteristics for population targeting to increase early detection and educate public and providers about the burden of disease. Understanding those audiences most in need, while not neglecting others at = the same time, will affect healthy behaviors, health screening, and participati= on in preventive health care. As information is accrued concerning these populations, legislative bodies will have evidence as to the impact that new laws and funding can have on their individual states.
Further, a major priority at this point is furth= er research, specifically on the activity and oncogenesis of HPV in the HPV-associated cancers. True numbers need to be generated as to the percent= age of these cancers actually caused by HPV as opposed to simply being coexiste= nt with HPV infection. As stated by Gillison et al:
“…Laboratory-based assays
should include demonstration of the specificity of the viral DNA in tumor c=
ell
nuclei, detection of viral oncogene expression, demonstration of a clonal a=
ssociation
between virus and tumor (e.g., integration, viral load, variant analysis), =
and
dependence of the malignant phenotype upon viral gene expression.”
A worldwide system=
atic
review did show that HPV16 and HPV18 accounted for almost all oncoge=
nic
HPV types detected in head and neck squamous cell cancer biopsies, suggesti=
ng
that HPV vaccines should also be relevant for this group of cancers. Another
related explanation of the shortcomings of recent studies is that they use
epidemiological surrogates such as anatomic site, age, and histology which =
may
misclassify HPV-associated or unassociated cancers that can alter vaccine
effectiveness estimates derived from pre-vaccine era and vaccine era
comparisons. Therefore, the HPV-etiologic fraction of the population must be
known and followed instead of the HPV-associated fractions for more accurate
results. Studies of this focus should be continued, as this was the route t=
hat
cervical cancers studies took to reach vaccine trials and implementation.
Even if the above concerns are addressed and completely understood, the original HPV vaccine debate of cost, safety, rig= ht to refuse, and moral issues remain. One ethical concern of oral cavity and oropharyngeal cancer is its link to sexual practices. As mentioned earlier,= a history of more than four oral sex partners has been linked to an increased risk of developing these cancers. Also, it has been noted that there is an increased HPV prevalence in cervical tissue compared to male carrier rates, while there is a higher rate of HPV-associated oropharyngeal cancer in men. Further, one study claimed that men had an increased risk of tonsillar canc= er when their wives had documented cervical dysplasia or cancer. However, it a= lso has been shown that this cannot be labeled as the only cause, as some patie= nts with oral cavity/oropharyngeal cancer report few sexual partners and no oral sex partners. Regardless, because at least some claim increased = risk with increased number of partners and oral sex partners, there is a negative stigma placed on the disease that raises similar moral questions as the deb= ate to vaccinate young girls to prevent cervical cancer, which is also linked to number of sexual partners, among other factors. Further, it has to be asked= if certain populations with these more “risky” sexual behaviors should be targ= eted for education or eligibility for vaccines.
Concerning funding, the Advisory Committee on Immunization Practices (ACIP) recommends the HPV vaccine in girls only because administration to females = has been established to be cost-effective. However, risks, benefits, and costs would have to be weighed again should vaccine administration be suggested in boys and/or adults for = oral cavity and oropharyngeal cancer. The same is true in infants if the vaccine were to be approved for prevention of RRP. Currently, the HPV vaccin= e is available through the federal Vaccines for Children (VFC) program in all 50 states, which provides vaccines for children ages nine to 18 who are covere= d by Medicaid, Alaskan-Native or Native American children, and some underinsured= or uninsured children. Reconfiguration of allocation of funds would have to oc= cur should the recommended coverage change, and this would be addressed by the legislature of each state. The issue of funding, whether through Medicaid and/or SCHIP, and for uninsured youth, has to be addressed, as well as deci= ding whether or not to require insurance companies to cover the vaccine.
Despite recommendations by ACIP, school vaccinat= ion requirements are decided by state legislatures, with some state legislatures granting regulatory bodies such as the Health Department the power to requi= re vaccines. In 2007, several states attempted to pass legislation to make the= HPV vaccine a school-entry requirement. While only the bill for Washington, DC = was enacted, from 2007 to the present, 41 other states have introduced legislat= ure to fund or educate the public about the HPV vaccine and at least 19 states[‡] have enacted these bills. Some states, such as New Hampshire, South Dakota,= and Washington, are providing the vaccine at no charge to all girls in the state who request vaccination. This could have interesting outcomes as the incide= nce of oral cavity, oropharyngeal, and laryngeal cancers, as well as recurrent respiratory papillomatosis, are monitored in individual states.
CONCLUSION
In summary, it has been noted that the burdens of HPV-associated oral cavity, oropharyngeal, and laryngeal cancer, as well as recurrent respiratory papillomatosis, are real issues in the United States. With the advent of the HPV vaccine for preventing cervical cancer, it will = be important to monitor changes in the incidence of these diseases, to investi= gate their pathophysiology and causal relationship to HPV infection, and to unde= rstand the distribution of disease in the United States. A dialogue on necessary mathematical modeling and cost-effectiveness studies to determine funding, = as well as anticipation of potentially difficult questions regarding distribut= ion of the vaccine will be important to address as research develops. The HPV vaccine could affect disease burden beyond cervical cancer, and the implications of this possibility should not be overlooked.
___________________________________________________________= _______
DISCUSSIONS:
Susan McCammon, MD;
HPV in Otolaryngology; September. =
30,
2010
Kathryn
has a very fascinating background in Public Health and Public Policy Resear=
ch
from her undergraduate days and we settled on this topic as a way to
investigate the occurrence of this topic in Otolaryngological literature as
well as one that has public health repercussions not necessarily in one whi=
ch
we will wind up doing but the debate and the rhetoric that surrounds the
establishment of vaccination as a potential anti-cancer targeted interventi=
on. This was not just a coy way of how to g=
et her
to say “oral sex” in all of her ENT interviews
In
Texas, the introduction of Gardisil was surrounded by a huge amount of
overblown rhetoric and controversy based on the fact that it was explicitly
casting cervical cancer as a sexually transmitted disease and behavior- or
vice-related disease burden and I remember when that first came out I though
“Hey, I know how to rehabilitate that – we’ll just make sure that everybody
knows that tonsil cancer and oropharyngeal cancer are also related to HPV.<=
span
style=3D'mso-spacerun:yes'> Interestingly, the research has gone the
other way and tarnished head and neck cancer with the same STD
condemnation.
We
as physicians can be open minded, tolerant, all we want but when you look at
the discussions and the controversies of the public policy makers, these are
certainly real issues. I think tha=
t was
a really good summary, Kathryn.
___________________________________________________________= __________
Vicente Resto, MD, PhD, FACS
HPV in Otolaryngology, September 3=
0,
2010
Nice
job, Kathryn. You raised some interesting issues regarding this topic. As physicians and scientists we try to =
come
up with mechanisms that make sense and use them as rational platforms for a=
ll
this policy debate. But those theo=
ries
are numerous and I think we really don’t understand what’s going on. They range all over from the idea that =
women
being exposed to cervical cancer, rather, HPV infection of the cervix which=
in
most cases is overwhelmingly cleared effectively multiple times. There are classic studies done in colle=
ge
that essentially paint a picture of college women being under continuous at=
tack
of HPV infection with successful clearance in most cases. And then you wonder whether that is an
inherent mechanism that then drives systemic immunity that then can explain=
why
women have less oropharyngeal cancer in comparison to men who are married to
women with a history of dysplasia. It
would be reasonable to think that it would be going the other way.
It
is evidently complex. There are ra=
cial
overtones in this as well because we did some work here looking at the
sero-database specifically looking at survival outcomes by race thinking th=
at
no one had looked at Hispanics. Th=
ere
have been studies that looked at outcomes in African-Americans and showed t=
hat
they were worse in general. What he
ended up finding was that the overall results were intermediate for Hispani=
cs,
worse than for Caucasians but better than for African-americans. However, when you case-matched and cont=
rolled
for primary tumor size, therapy, and a number of other variables those
differences completely disappear in a way that Hispanics now came to look j=
ust
like Caucasians did, suggesting that what drove the disparity was lack of
access to care, presentations with more advanced disease, and things of that
nature. Yet the disparity between
Hispanics and African-americans and Caucasians persisted. Interestingly that difference was drive=
n far
and away by disparity in the oropharynx.
Given what we know now, HPV is an immediate topic to consider and he then went a = step further and using known rates of HPV positivity began to do some modeling to actuarily understand whether those rates would explain the drive the dispar= ity and the result was, yes, they did. His actuarial data set which was quite massive, basically you can make a statem= ent that the disparity difference between African-americans and the others that persisted only in the oropharyngeal site is likely accounted for by HPV infection. There is a second study, independently confirming that, which is out of the University of Maryland w= ith a population of no Hispanics, and mostly African-americans where they found that Caucasians in their cohort were mostly positive as opposed to African-americans that were negative and again, that drove the difference.<= span style=3D'mso-spacerun:yes'> So, clearly there are racial components= that are going to come to be important in all this with profound effects on how public policy ultimately gets generated and implemented. So obviously race and socioeconomic sta= tus can be strong drivers in and of themselves within politics and government.<= span style=3D'mso-spacerun:yes'> It’s an interesting topic with much to = be done.
___________________________________________________________=
_
Harold Pine, MD, FAAP, Pediatric Otolaryngologist
HPV in Otolaryngology, September 3=
0,
2010
The
global public health burden attributable to human papilloma viruses is
considerable. Not only is this virus and its many subtypes a major pl=
ayer
in cervical cancer, it now clearly plays a role in certain cancers of the h=
ead
and neck. It makes me wonder for those in the pediatric population who suff=
er
from recurrent respiratory papillomatosis should have their virus sub typed
looking for the more virulent and oncogenic strains, ie 16 and 18. For
those children who require frequent trips to the operating room for debulki=
ng
of their disease, I do think it is a good idea to send off a biopsy every o=
nce
in a while to look for dysplasia or frank malignant transformation.
I
really applaud your interest in public health. It’s encouraging to see
our next generation of otolaryngologists so interested in the global commun=
ity.
From a pediatric perspective, I certainly favor the quadrivalent vaccine wh=
ich
covers not only sub types 16 and 18, but also covers 6 and 11, the players =
in
laryngeal papillomatosis. If this vaccine garners rapid universal support, I
wonder if future pediatric otolaryngologists will see less papillomas.
Perhaps it will be another topic for the history of medicine much like
laryngeal diphtheria. As for my colleagues in head and neck surgery, the
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###
[*] Defined as overlapping lesion of tong= ue; lateral wall of oropharynx; overlapping lesion of oropharynx; oropharynx, N= OS; pharynx, NOS; overlapping lesion of lip, oral cavity and pharynx.
[†] Quadrivalent vaccine contains aluminum hydroxyphsophate sulfate adjuvant, and is produced in yeast, while the bivalent vaccine cont= ains aluminum hydroxide and monophospholipid A and is produced in a baculovirus expression system.
[‡]
Colora=
do,
Indiana, Iowa, Louisiana, Maine, Maryland, Michigan, Minnesota, Nevada, New
Mexico, New York, North Carolina, North Dakota, Rhode Island, South Dakota,
Texas, Utah, Virginia and Washington.
The Human Papillomavirus Vaccine and its Implications in
Otolaryngology