October 5, 2011 — The sharp rise in oropharyngeal cancer associated with human papillomavirus (HPV) and its association with oral sex have been highlighted again, and this time has gained widespread media attention.
This new epidemic of HPV-positive oropharyngeal cancer has been brewing for a while now, as previously reported by Medscape Medical News.
The growing disease burden has reignited interest in whether HPV vaccination, currently directed at preventing cervical cancer, will be useful here, and reopened the debate about vaccinating boys as well as girls.
The latest findings were published online October 3 in the Journal of Clinical Oncology, and were highlighted in a press release issued by the American Society of Clinical Oncology (ASCO).
The researchers, headed by Maura Gillison MD, PhD, professor of medicine and Jeg Coughlin Chair of Cancer Research at The Ohio State University Comprehensive Cancer Center in Columbus, report that there has been a dramatic increase in the incidence of oropharyngeal cancer since 1984.
A growing majority of new cases (70%) are associated with HPV, and the vast majority of patients are male.
If the current trends continue, HPV-related oropharyngeal cancer will become the major form of head and neck cancer by 2020, and will become the leading HPV-associated cancer in the United States, surpassing cervical cancer, Dr. Gillison said in a statement.
"The increase may reflect increases in sexual behavior, including increases in oral sex," she added.
Legacy of Sexual Revolution?
Dr. Gillison previously told Medscape Medical News that the dramatic increase in HPV-related oropharyngeal cancer seen in recent years is a legacy of the sexual revolution in the 1960s.
"Our own work, using the SEER [Surveillance, Epidemiology, and End Results] database, shows a strong cohort effect, which means the greatest determinant of risk in any age group is the year in which you were born," Dr. Gillison pointed out.
"These cohort effects are largely driven by societal changes, and they tend to affect people first who are younger, because they are the people leading the behavioral changes," she explained.
During the 1960s, teenagers and young adults were more active sexually than previous generations, and having multiple sexual partners became more acceptable. "The more sexual partners you have, the greater the risk of contracting any sexually transmitted disease, including HPV," Dr. Gillison noted.
The time lag between an oral HPV infection and the development of HPV-related oropharyngeal cancer is between 15 and 30 years, and the age at which this cancer is usually diagnosed is 50 years or older.
The increase in this cancer that was seen in the 1990s and the 2000s is likely the result of young people participating in increased sexual activity in the 1960s and 1970s, Dr. Gillison reported.
Opportunity for HPV Vaccines?
The majority (90% to 95%) of the HPV-oropharyngeal cancer samples examined in this study were associated with one subtype of the virus, HPV-16.
This is one of the HPV subtypes that is targeted by both of the currently available HPV vaccines used for cervical cancer prevention (Gardasil from Merck & Co, which protects against HPV subtypes 6, 11, 16, and 18; and Ceravix,from GlaxoSmithKline, which protects against HPV subtypes 16 and 18).
"With HPV vaccines, we have a great opportunity to potentially prevent oropharynx cancers in future generations — including in boys and men," Dr. Gillison said. However, she pointed out that studies to assess the efficacy of these vaccines in preventing oral HPV infections will be needed, and so far these have not been carried out. Such a trial was planned, but the pharmaceutical manufacturers pulled out, she said.
The potential for a role for HPV vaccines is highlighted in the press release from ASCO, and in an editorial accompanying the study.
"The findings could have particular relevance for the HPV vaccine administration policy," said Gregory Masters MD, FACP, a head and neck specialist in Newark, New Jersey, and a member of the ASCO Cancer Communications Committee. "We are encouraged by what the availability of HPV vaccines may be able to do to prevent these cancers now that we have a clearer understanding of causation".
The editorial, by James Rocco, MD, PhD, and Edmund Mroz, PhD, from the Massachusetts General Hospital in Boston, and Arlene Forastiere, MD, from the Johns Hopkins Medical Institutions in Baltimore, Maryland, notes that it is "expected" that HPV vaccination will reduce the incidence of HPV infections and oropharyngeal cancer, but this is "not yet documented."
"Direct tests of this efficacy are needed, given that prevention through vaccination will almost certainly be the ultimate solution to HPV-positive oropharyngeal cancer," they declare.
Current HPV vaccines are approved for use in girls for cervical cancer prevention, although the quadrivalent vaccine Gardasil is also approved for use in males and females to offer protection against genital warts and anal cancer (associated with HPV subtypes 6 and 11). However, there has not been any wholesale recommendation for the use of HPV vaccines in boys, even though some experts have argued that such a use would improve the overall efficacy of protecting against HPV genital infections.
Now that HPV-associated oral cancers have been added to the mix, the argument for using HPV vaccines in boys becomes more forceful. Current recommendations for vaccinating males "must be reconsidered in light of the growing incidence of male HPV-positive oropharyngeal cancer demonstrated in the current report," the editorialists write.
Because HPV cancers are now known to affect both men and women, and because current HPV vaccines are only effective before infection is established, the editorialists recommend that primary care providers inform parents of both boys and girls "about the risks of HPV-associated tumors and the likely reduction in risk provided by the vaccination."
Implications for Clinical Practice
In addition to the potential of HPV vaccination, the editorialists highlight 2 important implications for clinical practice from the latest study.
Now that significant risk factors for both HPV-positive and HPV-negative oropharyngeal cancer are well known, clinicians should encourage patients to "minimize behaviors that put them at risk from either form," they write.
"Third, oncologists should routinely test all patients with oropharyngeal cancer for HPV status, if for no other reason than to refine prognosis," the editorialists recommend. Such testing is already part of clinical trial design, and there is hope that the distinction between HPV-positive and HPV-negative cancers "may soon assist in selecting treatments," they add.
The 2 forms of this cancer have major differences in outcomes, they point out. HPV-positive oropharyngeal cancer is diagnosed at a younger age and has a good prognosis, with "substantial long-term survival," they note. This presents an urgent need for a lower-intensity therapy that maintains control of the disease while avoiding the significant short- and long-term morbidity of current therapy.
Small Sample Size
The study that provoked all of this commentary, and that reconstructs the recent history of oropharyngeal cancer in the United States, is based on only 271 cancer samples, the editorialist point out. But they add that "we are unlikely to get a better picture," because this study used all the samples that were available.
The samples came from 3 states — California (Los Angeles), Hawaii, and Iowa — from SEER registries that participate in the Residual Tissue Repositories program. Samples were only available for less than 5% of patients in these registries, the editorialists point out, and they estimate that during the 2-decade study (1984 to 2004), there were around 200,000 patients with oropharyngeal cancer in the United States.
In their analysis, the researchers used 69 samples of cervical cancer as positive controls and samples of 27 gastric cancers as negative controls.
The prevalence of HPV-associated oropharyngeal cancer increased significantly over the course of the study. HPV prevalence increased from 16.3% during the period from 1984 to 1989, to 71.1% during the period from 2000 to 2004.
First author Anil Chatrurvedi, PhD, from the National Cancer Institutes, and colleagues used these findings to estimate that the population-level incidence of HPV-positive oropharyngeal cancers increased by 22% from 1998 to 2004 (from 0.8 to 2.6 per 100,000 individuals), whereas the incidence of HPV-negative cancer declined by 50% (from 2.0 to 1.0 per 100,000 individuals).
The decline in HPV-negative oropharyngeal cancer parallels a decline in smoking in the United States; the increasing incidence of HPV-positive cancer "perhaps arises from increased oral sex and oral HPV exposure over time," the researchers note. In support of this theory, they cite data showing an increase in the prevalence of genital herpes simplex virus (HSV), both type 1 and type 2, and genital warts among recent birth cohorts in the United States, and note that all 3 are "accepted surrogates" for oral sex (HSV1), risky sexual behavior (HSV2), and HPV exposure (genital warts). The predominant rise in oropharyngeal cancer among the young is consistent with this scenario, they add.
However, the reason the increase in HPV-positive oropharyngeal cancer is so pronounced among males and whites "remains unexplained," they add.
Burden of Disease
On the basis of their findings, the researchers estimate that by the year 2020, the annual number of HPV-positive oropharyngeal cancers (approximately 8700 patients, with the majority of these — around 7400 — occurring in men) will surpass the annual number of cervical cancers (approximately 7700 patients).
This is based on a conservative assumption of 70% of oropharyngeal cancer being HPV-positive (which was the case in 2004, but because the trend is increasing, it might be even higher now).
So far, cervical cancer has been the focus of prophylactic HPV vaccination; this is justified, the researchers note, because of the substantially higher burden of cervical precancers, compared with invasive cervical cancers or oropharyngeal cancers, in the United States.
However, the rising burden of HPV-positive oropharyngeal cancer requires that attention focus on vaccination to prevent oral HPV infection, especially because there is no screening currently available for oropharyngeal cancer. "The high efficacy of HPV vaccines in preventing extracervical infections among women (e.g., vagina and vulva) and penile and anal infections among men implies that efficacy may be comparable against oral HPV infections," they write.
Dr. Gillison reports serving as a consultant for Merck & Co, GlaxoSmithKline, Amgen, and Bristol-Myers Squibb. The editorialists disclosed no relevant financial relationships.
J Clin Oncol. Published online October 3, 2011. Abstract, Editorial
This new epidemic of HPV-positive oropharyngeal cancer has been brewing for a while now, as previously reported by Medscape Medical News.
The growing disease burden has reignited interest in whether HPV vaccination, currently directed at preventing cervical cancer, will be useful here, and reopened the debate about vaccinating boys as well as girls.
The latest findings were published online October 3 in the Journal of Clinical Oncology, and were highlighted in a press release issued by the American Society of Clinical Oncology (ASCO).
The researchers, headed by Maura Gillison MD, PhD, professor of medicine and Jeg Coughlin Chair of Cancer Research at The Ohio State University Comprehensive Cancer Center in Columbus, report that there has been a dramatic increase in the incidence of oropharyngeal cancer since 1984.
A growing majority of new cases (70%) are associated with HPV, and the vast majority of patients are male.
If the current trends continue, HPV-related oropharyngeal cancer will become the major form of head and neck cancer by 2020, and will become the leading HPV-associated cancer in the United States, surpassing cervical cancer, Dr. Gillison said in a statement.
"The increase may reflect increases in sexual behavior, including increases in oral sex," she added.
Legacy of Sexual Revolution?
Dr. Gillison previously told Medscape Medical News that the dramatic increase in HPV-related oropharyngeal cancer seen in recent years is a legacy of the sexual revolution in the 1960s.
"Our own work, using the SEER [Surveillance, Epidemiology, and End Results] database, shows a strong cohort effect, which means the greatest determinant of risk in any age group is the year in which you were born," Dr. Gillison pointed out.
"These cohort effects are largely driven by societal changes, and they tend to affect people first who are younger, because they are the people leading the behavioral changes," she explained.
During the 1960s, teenagers and young adults were more active sexually than previous generations, and having multiple sexual partners became more acceptable. "The more sexual partners you have, the greater the risk of contracting any sexually transmitted disease, including HPV," Dr. Gillison noted.
The time lag between an oral HPV infection and the development of HPV-related oropharyngeal cancer is between 15 and 30 years, and the age at which this cancer is usually diagnosed is 50 years or older.
The increase in this cancer that was seen in the 1990s and the 2000s is likely the result of young people participating in increased sexual activity in the 1960s and 1970s, Dr. Gillison reported.
Opportunity for HPV Vaccines?
The majority (90% to 95%) of the HPV-oropharyngeal cancer samples examined in this study were associated with one subtype of the virus, HPV-16.
This is one of the HPV subtypes that is targeted by both of the currently available HPV vaccines used for cervical cancer prevention (Gardasil from Merck & Co, which protects against HPV subtypes 6, 11, 16, and 18; and Ceravix,from GlaxoSmithKline, which protects against HPV subtypes 16 and 18).
"With HPV vaccines, we have a great opportunity to potentially prevent oropharynx cancers in future generations — including in boys and men," Dr. Gillison said. However, she pointed out that studies to assess the efficacy of these vaccines in preventing oral HPV infections will be needed, and so far these have not been carried out. Such a trial was planned, but the pharmaceutical manufacturers pulled out, she said.
The potential for a role for HPV vaccines is highlighted in the press release from ASCO, and in an editorial accompanying the study.
"The findings could have particular relevance for the HPV vaccine administration policy," said Gregory Masters MD, FACP, a head and neck specialist in Newark, New Jersey, and a member of the ASCO Cancer Communications Committee. "We are encouraged by what the availability of HPV vaccines may be able to do to prevent these cancers now that we have a clearer understanding of causation".
The editorial, by James Rocco, MD, PhD, and Edmund Mroz, PhD, from the Massachusetts General Hospital in Boston, and Arlene Forastiere, MD, from the Johns Hopkins Medical Institutions in Baltimore, Maryland, notes that it is "expected" that HPV vaccination will reduce the incidence of HPV infections and oropharyngeal cancer, but this is "not yet documented."
"Direct tests of this efficacy are needed, given that prevention through vaccination will almost certainly be the ultimate solution to HPV-positive oropharyngeal cancer," they declare.
Current HPV vaccines are approved for use in girls for cervical cancer prevention, although the quadrivalent vaccine Gardasil is also approved for use in males and females to offer protection against genital warts and anal cancer (associated with HPV subtypes 6 and 11). However, there has not been any wholesale recommendation for the use of HPV vaccines in boys, even though some experts have argued that such a use would improve the overall efficacy of protecting against HPV genital infections.
Now that HPV-associated oral cancers have been added to the mix, the argument for using HPV vaccines in boys becomes more forceful. Current recommendations for vaccinating males "must be reconsidered in light of the growing incidence of male HPV-positive oropharyngeal cancer demonstrated in the current report," the editorialists write.
Because HPV cancers are now known to affect both men and women, and because current HPV vaccines are only effective before infection is established, the editorialists recommend that primary care providers inform parents of both boys and girls "about the risks of HPV-associated tumors and the likely reduction in risk provided by the vaccination."
Implications for Clinical Practice
In addition to the potential of HPV vaccination, the editorialists highlight 2 important implications for clinical practice from the latest study.
Now that significant risk factors for both HPV-positive and HPV-negative oropharyngeal cancer are well known, clinicians should encourage patients to "minimize behaviors that put them at risk from either form," they write.
"Third, oncologists should routinely test all patients with oropharyngeal cancer for HPV status, if for no other reason than to refine prognosis," the editorialists recommend. Such testing is already part of clinical trial design, and there is hope that the distinction between HPV-positive and HPV-negative cancers "may soon assist in selecting treatments," they add.
The 2 forms of this cancer have major differences in outcomes, they point out. HPV-positive oropharyngeal cancer is diagnosed at a younger age and has a good prognosis, with "substantial long-term survival," they note. This presents an urgent need for a lower-intensity therapy that maintains control of the disease while avoiding the significant short- and long-term morbidity of current therapy.
Small Sample Size
The study that provoked all of this commentary, and that reconstructs the recent history of oropharyngeal cancer in the United States, is based on only 271 cancer samples, the editorialist point out. But they add that "we are unlikely to get a better picture," because this study used all the samples that were available.
The samples came from 3 states — California (Los Angeles), Hawaii, and Iowa — from SEER registries that participate in the Residual Tissue Repositories program. Samples were only available for less than 5% of patients in these registries, the editorialists point out, and they estimate that during the 2-decade study (1984 to 2004), there were around 200,000 patients with oropharyngeal cancer in the United States.
In their analysis, the researchers used 69 samples of cervical cancer as positive controls and samples of 27 gastric cancers as negative controls.
The prevalence of HPV-associated oropharyngeal cancer increased significantly over the course of the study. HPV prevalence increased from 16.3% during the period from 1984 to 1989, to 71.1% during the period from 2000 to 2004.
First author Anil Chatrurvedi, PhD, from the National Cancer Institutes, and colleagues used these findings to estimate that the population-level incidence of HPV-positive oropharyngeal cancers increased by 22% from 1998 to 2004 (from 0.8 to 2.6 per 100,000 individuals), whereas the incidence of HPV-negative cancer declined by 50% (from 2.0 to 1.0 per 100,000 individuals).
The decline in HPV-negative oropharyngeal cancer parallels a decline in smoking in the United States; the increasing incidence of HPV-positive cancer "perhaps arises from increased oral sex and oral HPV exposure over time," the researchers note. In support of this theory, they cite data showing an increase in the prevalence of genital herpes simplex virus (HSV), both type 1 and type 2, and genital warts among recent birth cohorts in the United States, and note that all 3 are "accepted surrogates" for oral sex (HSV1), risky sexual behavior (HSV2), and HPV exposure (genital warts). The predominant rise in oropharyngeal cancer among the young is consistent with this scenario, they add.
However, the reason the increase in HPV-positive oropharyngeal cancer is so pronounced among males and whites "remains unexplained," they add.
Burden of Disease
On the basis of their findings, the researchers estimate that by the year 2020, the annual number of HPV-positive oropharyngeal cancers (approximately 8700 patients, with the majority of these — around 7400 — occurring in men) will surpass the annual number of cervical cancers (approximately 7700 patients).
This is based on a conservative assumption of 70% of oropharyngeal cancer being HPV-positive (which was the case in 2004, but because the trend is increasing, it might be even higher now).
So far, cervical cancer has been the focus of prophylactic HPV vaccination; this is justified, the researchers note, because of the substantially higher burden of cervical precancers, compared with invasive cervical cancers or oropharyngeal cancers, in the United States.
However, the rising burden of HPV-positive oropharyngeal cancer requires that attention focus on vaccination to prevent oral HPV infection, especially because there is no screening currently available for oropharyngeal cancer. "The high efficacy of HPV vaccines in preventing extracervical infections among women (e.g., vagina and vulva) and penile and anal infections among men implies that efficacy may be comparable against oral HPV infections," they write.
Dr. Gillison reports serving as a consultant for Merck & Co, GlaxoSmithKline, Amgen, and Bristol-Myers Squibb. The editorialists disclosed no relevant financial relationships.
J Clin Oncol. Published online October 3, 2011. Abstract, Editorial
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