Pediatricians’ knowledge of HPV-related diseases, limited immunization of boys hinders uptake

Alexander Kenneth
Kenneth A. Alexander

Editor’s note: In this three-part series, Kenneth A. Alexander, MD, PhD, Chief of the Division of Infectious Diseases in the Department of Pediatrics at Nemours Children's Hospital in Orlando, Florida, reviews issues surrounding uptake of the HPV vaccine. Part two of the series examines barriers that prevent more children from being immunized, including lack of familiarity with HPV-related diseases in the pediatric setting and limited vaccination of boys.

An underlying issue related to uptake of the HPV vaccine is that pediatricians are being asked to vaccinate against a disease that they don’t routinely see. Pediatricians are familiar with measles, mumps, rubella and polio. We know the tragedy of measles encephalitis, and we have seen strokes caused by pneumococcal meningitis; the world is still seeing the paralysis caused by polio. But pediatricians don’t know cervical cancer. This disease strikes an adult population at mid-life, in their 40s and 50s — not our patients.

What we as pediatricians must come to appreciate is that, for every child in the United States who dies of meningococcal disease, there are 40 women who die of cervical cancer. These women who die are our mothers, daughters, sisters, aunts, nieces, colleagues and friends. Furthermore, pediatricians need to understand the ravages of cervical disease. The fact that we don’t see these cancers in our patients doesn’t get us off the hook for not vaccinating against them anymore than the fact that we aren’t trauma surgeons gets us off the hook for not talking about seatbelts and firearms. As pediatricians in the year 2018, we need to proudly embrace the fact that we’re now in the business of cancer prevention.

Cancer prevention is neither easy nor entirely natural for pediatricians. Although we are all comfortable with babies and young children, many of us feel more challenged by adolescents, especially when discussing sexuality. In some ways, pediatricians need to grow up just as much as parents need to grow up. We should not be afraid to talk about sexuality when talking about how safe sexual practices saves lives. Certainly, we learned from the AIDS epidemic that silence leads to death; the same principle may apply to HPV vaccination.

It is important to reiterate that the main reason that children aren’t immunized against HPV is not because parents are worried about sexuality; children aren’t immunized against HPV because doctors don’t recommend immunization. As pediatricians, we must remind parents and clinicians that the Advisory Committee on Immunization Practices unanimously recommended HPV vaccination and that they used the word “recommended.” If the ACIP had meant that “HPV vaccination is a good idea, do it if you want to,” they would have said that HPV vaccination should be encouraged when, in fact, what they said is that HPV vaccination is recommended. The use of this word puts that vaccine recommendation on par with the recommendations for measles and polio vaccinations.

These recommendations do not tell pediatricians to vaccinate against HPV “if you want to.” The recommendations say that HPV immunization is what good pediatricians do. In addition, if we take this argument further (keeping in mind that I am no legal scholar), there will soon be some woman whose pediatrician didn’t recommend HPV immunization. Because she is unprotected, this woman will have trouble with her cervix. Because she was not advised to receive a recommended vaccine, she will seek legal recourse. I worry that the nonrecommending pediatrician will be in an indefensible position.

Immunizing men to protect men

Immunizing boys is an interesting and important issue. A lot of people naturally say, ‘I want to immunize boys to protect girls.’ I’m all for that; I have two daughters and I think immunizing men to protect women is a great idea. That said, my daughters were immunized long ago. My real concern is that we immunize our sons to protect them against HPV-associated diseases that men get, including genital warts, anal cancers, penile cancers and oropharyngeal cancers. Regarding the last disease, oropharyngeal cancer, it is important to keep in mind that a compelling body of data now demonstrates that about two-thirds of oropharyngeal cancers are caused by oncogenic types of HPV, primarily HPV16. Head and neck cancers are men’s diseases. If you visit the American Cancer Society website, and you look at the number of men who will die of head and neck cancer this year, you will see many cases. If you then assume that two-thirds of those cases of head and neck cancer are caused by vaccine-preventable types of HPV, you soon realize that there are now more men dying of HPV-associated head and neck cancers than there are women dying of cervical cancer.

Given this evidence about the high prevalence of HPV-associated head and neck cancers in men, you may ask: Why is the head and neck cancer discussion new in the HPV world? There are two reasons. First, we have known for a long time that strains of HPV cause cervical cancer. Consequently, there is a lot to talk about, with excellent clinical data that show the HPV vaccine prevents cervical disease; that’s what all the major clinical trials were about. The understanding that strains of HPV cause head and neck cancers is a newer realization. The data showing that strains of HPV cause oropharyngeal cancer are comparatively new; much of it was collected in the past 15 years. Because the realization that strains of HPV cause oropharyngeal cancers is new, we know less, and there has therefore been less to talk about with patients and families.

The second reason that the discussions about head and neck cancers are new is because we don’t have as many data about the impact of the HPV vaccine on these cancers. No one has completed a trial to see if the HPV vaccine prevents head and neck cancers, although we know that head and neck cancers are caused by vaccine-type viruses, so we anticipate that the vaccine will prevent HPV-associated oropharyngeal cancers.

An important consideration with clinical trials of an HPV vaccine, in the case of cervical cancer, is this: We have well-described precancerous states (cervical intraepithelial neoplasia grades 2 and 3). These are the precursor stages to cervical cancer. Because we understand how CIN2 and CIN3 progress to cervical cancer, these precancerous states can be used as clinical endpoints; this prevents us from having to wait until a woman in a clinical trial develops cancer (to say nothing of the fact that letting a trial subject progress to cancer would be highly unethical). In large part, clinical trials of HPV vaccines have demonstrated that the vaccines prevented all the precancerous stages that precede cervical cancer. With this understanding, and our knowledge of how CIN2 and CIN3 progress to cancer, we made the leap to the conclusion that the HPV vaccine would not only prevent CIN2 and CIN3, but cancer, too. Fortunately, as vaccinated populations continue to be followed, we now have evidence that the vaccines do prevent cancer.

In the case of oropharyngeal cancers, however, we do not yet have a well-established, premalignant condition or conditions that would allow us to conduct a clinical trial. Furthermore, given the ability of the vaccine to prevent other diseases in males, a placebo-controlled study to determine if the vaccine prevented oropharyngeal cancer would be unethical. Here, we will simply have to wait for the population studies. Boys in many countries are being immunized; we will eventually determine whether immunization of those boys prevents cancer as they move into mid-adult life. I’m optimistic that this will, indeed, be the case. In the meantime, we must advocate HPV immunization for boys just as we do for girls.

Disclosure: Alexander reports serving as a consultant and as a speaker for Merck and for MSD, the manufacturer of the 9-valent HPV vaccine.

Alexander Kenneth
Kenneth A. Alexander

Editor’s note: In this three-part series, Kenneth A. Alexander, MD, PhD, Chief of the Division of Infectious Diseases in the Department of Pediatrics at Nemours Children's Hospital in Orlando, Florida, reviews issues surrounding uptake of the HPV vaccine. Part two of the series examines barriers that prevent more children from being immunized, including lack of familiarity with HPV-related diseases in the pediatric setting and limited vaccination of boys.

An underlying issue related to uptake of the HPV vaccine is that pediatricians are being asked to vaccinate against a disease that they don’t routinely see. Pediatricians are familiar with measles, mumps, rubella and polio. We know the tragedy of measles encephalitis, and we have seen strokes caused by pneumococcal meningitis; the world is still seeing the paralysis caused by polio. But pediatricians don’t know cervical cancer. This disease strikes an adult population at mid-life, in their 40s and 50s — not our patients.

What we as pediatricians must come to appreciate is that, for every child in the United States who dies of meningococcal disease, there are 40 women who die of cervical cancer. These women who die are our mothers, daughters, sisters, aunts, nieces, colleagues and friends. Furthermore, pediatricians need to understand the ravages of cervical disease. The fact that we don’t see these cancers in our patients doesn’t get us off the hook for not vaccinating against them anymore than the fact that we aren’t trauma surgeons gets us off the hook for not talking about seatbelts and firearms. As pediatricians in the year 2018, we need to proudly embrace the fact that we’re now in the business of cancer prevention.

Cancer prevention is neither easy nor entirely natural for pediatricians. Although we are all comfortable with babies and young children, many of us feel more challenged by adolescents, especially when discussing sexuality. In some ways, pediatricians need to grow up just as much as parents need to grow up. We should not be afraid to talk about sexuality when talking about how safe sexual practices saves lives. Certainly, we learned from the AIDS epidemic that silence leads to death; the same principle may apply to HPV vaccination.

It is important to reiterate that the main reason that children aren’t immunized against HPV is not because parents are worried about sexuality; children aren’t immunized against HPV because doctors don’t recommend immunization. As pediatricians, we must remind parents and clinicians that the Advisory Committee on Immunization Practices unanimously recommended HPV vaccination and that they used the word “recommended.” If the ACIP had meant that “HPV vaccination is a good idea, do it if you want to,” they would have said that HPV vaccination should be encouraged when, in fact, what they said is that HPV vaccination is recommended. The use of this word puts that vaccine recommendation on par with the recommendations for measles and polio vaccinations.

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These recommendations do not tell pediatricians to vaccinate against HPV “if you want to.” The recommendations say that HPV immunization is what good pediatricians do. In addition, if we take this argument further (keeping in mind that I am no legal scholar), there will soon be some woman whose pediatrician didn’t recommend HPV immunization. Because she is unprotected, this woman will have trouble with her cervix. Because she was not advised to receive a recommended vaccine, she will seek legal recourse. I worry that the nonrecommending pediatrician will be in an indefensible position.

Immunizing men to protect men

Immunizing boys is an interesting and important issue. A lot of people naturally say, ‘I want to immunize boys to protect girls.’ I’m all for that; I have two daughters and I think immunizing men to protect women is a great idea. That said, my daughters were immunized long ago. My real concern is that we immunize our sons to protect them against HPV-associated diseases that men get, including genital warts, anal cancers, penile cancers and oropharyngeal cancers. Regarding the last disease, oropharyngeal cancer, it is important to keep in mind that a compelling body of data now demonstrates that about two-thirds of oropharyngeal cancers are caused by oncogenic types of HPV, primarily HPV16. Head and neck cancers are men’s diseases. If you visit the American Cancer Society website, and you look at the number of men who will die of head and neck cancer this year, you will see many cases. If you then assume that two-thirds of those cases of head and neck cancer are caused by vaccine-preventable types of HPV, you soon realize that there are now more men dying of HPV-associated head and neck cancers than there are women dying of cervical cancer.

Given this evidence about the high prevalence of HPV-associated head and neck cancers in men, you may ask: Why is the head and neck cancer discussion new in the HPV world? There are two reasons. First, we have known for a long time that strains of HPV cause cervical cancer. Consequently, there is a lot to talk about, with excellent clinical data that show the HPV vaccine prevents cervical disease; that’s what all the major clinical trials were about. The understanding that strains of HPV cause head and neck cancers is a newer realization. The data showing that strains of HPV cause oropharyngeal cancer are comparatively new; much of it was collected in the past 15 years. Because the realization that strains of HPV cause oropharyngeal cancers is new, we know less, and there has therefore been less to talk about with patients and families.

PAGE BREAK

The second reason that the discussions about head and neck cancers are new is because we don’t have as many data about the impact of the HPV vaccine on these cancers. No one has completed a trial to see if the HPV vaccine prevents head and neck cancers, although we know that head and neck cancers are caused by vaccine-type viruses, so we anticipate that the vaccine will prevent HPV-associated oropharyngeal cancers.

An important consideration with clinical trials of an HPV vaccine, in the case of cervical cancer, is this: We have well-described precancerous states (cervical intraepithelial neoplasia grades 2 and 3). These are the precursor stages to cervical cancer. Because we understand how CIN2 and CIN3 progress to cervical cancer, these precancerous states can be used as clinical endpoints; this prevents us from having to wait until a woman in a clinical trial develops cancer (to say nothing of the fact that letting a trial subject progress to cancer would be highly unethical). In large part, clinical trials of HPV vaccines have demonstrated that the vaccines prevented all the precancerous stages that precede cervical cancer. With this understanding, and our knowledge of how CIN2 and CIN3 progress to cancer, we made the leap to the conclusion that the HPV vaccine would not only prevent CIN2 and CIN3, but cancer, too. Fortunately, as vaccinated populations continue to be followed, we now have evidence that the vaccines do prevent cancer.

In the case of oropharyngeal cancers, however, we do not yet have a well-established, premalignant condition or conditions that would allow us to conduct a clinical trial. Furthermore, given the ability of the vaccine to prevent other diseases in males, a placebo-controlled study to determine if the vaccine prevented oropharyngeal cancer would be unethical. Here, we will simply have to wait for the population studies. Boys in many countries are being immunized; we will eventually determine whether immunization of those boys prevents cancer as they move into mid-adult life. I’m optimistic that this will, indeed, be the case. In the meantime, we must advocate HPV immunization for boys just as we do for girls.

Disclosure: Alexander reports serving as a consultant and as a speaker for Merck and for MSD, the manufacturer of the 9-valent HPV vaccine.