In reply: Human papillomavirus

In Reply: We would like to thank Dr. Lichtenberg for giving us the opportunity to clarify and expand on questions regarding HPV vaccine efficacy.

Our statement “HPV immunization can prevent up to 70% of cases of cervical cancer due to HPV as well as 90% of genital warts” was based on a statement by Thaxton and Waxman, ie, that immunization against HPV types 16 and 18 has the potential to prevent 70% of cancers of the cervix plus a large percentage of other lower anogenital tract cancers.¹ This was meant to describe the prevention potential of the quadrivalent vaccine. The currently available Gardasil 9 targets the HPV types that account for 90% of cervical cancers,² with projected effectiveness likely to vary based on geographic variation in HPV subtypes, ranging from 86.5% in Australia to 92% in North America.³ It is difficult to precisely calculate the effectiveness of HPV vaccination alone, given that cervical cancer prevention is twofold, with primary vaccination and secondary screening (with several notable updates to US national screening guidelines during the same time frame as vaccine development).⁴

It is true that the 29% decrease in US cervical cancer incidence rates during the years 2011–2014 compared with 2003–2006 is less than the predicted 70%.⁵ However, not all eligible US females are vaccinated; according to reports from the US Centers for Disease Control and Prevention, 49% of adolescents were appropriately immunized against HPV in 2017, an increase over the rate of only 35% in 2014.⁶ Low vaccination rates undoubtedly negatively impact any benefits from herd immunity, though the exact benefits of this population immunity are difficult to quantify.⁷

In Australia, a national school-based HPV vaccination program was initiated in 2007, making the vaccine available for free. Over 70% of girls ages 12 and 13 were vaccinated, and follow-up within the same decade showed a greater than 90% reduction in genital warts, as well as a reduction in high-grade cervical lesions.⁸ In addition, the incidence of genital warts in unvaccinated heterosexual males during the prevaccination vs the vaccination period decreased by up to 81% (a marker of herd immunity).⁹

In the US, the HPV subtypes found in the quadrivalent vaccine decreased by 71% in those ages 14 to 19, within 8 years of vaccine introduction.¹⁰ An analysis of US state cancer registries between 2009 and 2012 showed that in Michigan, the rates of high-grade, precancerous lesions declined by 37% each year for women ages 15 to 19, thought to be due to changes in screening and vaccination guidelines.¹¹ Similarly, an analysis of 9 million privately insured US females showed that the presence of high-grade precancerous lesions significantly decreased between the years 2007 and 2014 in those ages 15 to 24 (vaccinated individuals), but not in those ages 25 to 39 (unvaccinated individuals).¹² Most recently, a study of 10,206 women showed a 21.9% decrease in cervical intraepithelial neoplasia grade 2 or worse lesions due to HPV subtypes 16 or 18 in those who have received at least 1 dose of the vaccine; reduced rates in unvaccinated women were also seen, representing first evidence of herd immunity in the United States.¹³ In contrast, the rates of high-grade lesions due to nonvaccine HPV subtypes remained constant. Given that progression to cervical cancer can take 10 to 15 years or longer after HPV infection, true vaccine benefits will emerge once increased vaccination rates are achieved and after at least a decade of follow-up.

We applaud Dr. Lichtenberg’s efforts to clarify vaccine efficacy for appropriate counseling, as this is key to ensuring patient trust. Immunization fears have fueled the re-emergence of vaccine-preventable illnesses across the world. Given the wave of vaccine misinformation on the Internet, we all face patients and family members skeptical of vaccine efficacy and safety. Those requesting more information deserve an honest, informed discussion with their provider. Interestingly, however, among 955 unvaccinated women, the belief of not being at risk for HPV was the most common reason for not receiving the vaccine.¹⁴ Effective education can be achieved by focusing on the personal risks of HPV to the patient, as well as the overall favorable risk vs benefits of vaccination. Quoting an exact rate of cancer reduction is likely a less effective counseling strategy, and these efficacy estimates will change as vaccination rates and HPV prevalence within the population change over time.

In Reply: We would like to thank Dr. Lichtenberg for giving us the opportunity to clarify and expand on questions regarding HPV vaccine efficacy.

Our statement “HPV immunization can prevent up to 70% of cases of cervical cancer due to HPV as well as 90% of genital warts” was based on a statement by Thaxton and Waxman, ie, that immunization against HPV types 16 and 18 has the potential to prevent 70% of cancers of the cervix plus a large percentage of other lower anogenital tract cancers.¹ This was meant to describe the prevention potential of the quadrivalent vaccine. The currently available Gardasil 9 targets the HPV types that account for 90% of cervical cancers,² with projected effectiveness likely to vary based on geographic variation in HPV subtypes, ranging from 86.5% in Australia to 92% in North America.³ It is difficult to precisely calculate the effectiveness of HPV vaccination alone, given that cervical cancer prevention is twofold, with primary vaccination and secondary screening (with several notable updates to US national screening guidelines during the same time frame as vaccine development).⁴

It is true that the 29% decrease in US cervical cancer incidence rates during the years 2011–2014 compared with 2003–2006 is less than the predicted 70%.⁵ However, not all eligible US females are vaccinated; according to reports from the US Centers for Disease Control and Prevention, 49% of adolescents were appropriately immunized against HPV in 2017, an increase over the rate of only 35% in 2014.⁶ Low vaccination rates undoubtedly negatively impact any benefits from herd immunity, though the exact benefits of this population immunity are difficult to quantify.⁷

In Australia, a national school-based HPV vaccination program was initiated in 2007, making the vaccine available for free. Over 70% of girls ages 12 and 13 were vaccinated, and follow-up within the same decade showed a greater than 90% reduction in genital warts, as well as a reduction in high-grade cervical lesions.⁸ In addition, the incidence of genital warts in unvaccinated heterosexual males during the prevaccination vs the vaccination period decreased by up to 81% (a marker of herd immunity).⁹

In the US, the HPV subtypes found in the quadrivalent vaccine decreased by 71% in those ages 14 to 19, within 8 years of vaccine introduction.¹⁰ An analysis of US state cancer registries between 2009 and 2012 showed that in Michigan, the rates of high-grade, precancerous lesions declined by 37% each year for women ages 15 to 19, thought to be due to changes in screening and vaccination guidelines.¹¹ Similarly, an analysis of 9 million privately insured US females showed that the presence of high-grade precancerous lesions significantly decreased between the years 2007 and 2014 in those ages 15 to 24 (vaccinated individuals), but not in those ages 25 to 39 (unvaccinated individuals).¹² Most recently, a study of 10,206 women showed a 21.9% decrease in cervical intraepithelial neoplasia grade 2 or worse lesions due to HPV subtypes 16 or 18 in those who have received at least 1 dose of the vaccine; reduced rates in unvaccinated women were also seen, representing first evidence of herd immunity in the United States.¹³ In contrast, the rates of high-grade lesions due to nonvaccine HPV subtypes remained constant. Given that progression to cervical cancer can take 10 to 15 years or longer after HPV infection, true vaccine benefits will emerge once increased vaccination rates are achieved and after at least a decade of follow-up.

We applaud Dr. Lichtenberg’s efforts to clarify vaccine efficacy for appropriate counseling, as this is key to ensuring patient trust. Immunization fears have fueled the re-emergence of vaccine-preventable illnesses across the world. Given the wave of vaccine misinformation on the Internet, we all face patients and family members skeptical of vaccine efficacy and safety. Those requesting more information deserve an honest, informed discussion with their provider. Interestingly, however, among 955 unvaccinated women, the belief of not being at risk for HPV was the most common reason for not receiving the vaccine.¹⁴ Effective education can be achieved by focusing on the personal risks of HPV to the patient, as well as the overall favorable risk vs benefits of vaccination. Quoting an exact rate of cancer reduction is likely a less effective counseling strategy, and these efficacy estimates will change as vaccination rates and HPV prevalence within the population change over time.

In Reply: We would like to thank Dr. Lichtenberg for giving us the opportunity to clarify and expand on questions regarding HPV vaccine efficacy.

Our statement “HPV immunization can prevent up to 70% of cases of cervical cancer due to HPV as well as 90% of genital warts” was based on a statement by Thaxton and Waxman, ie, that immunization against HPV types 16 and 18 has the potential to prevent 70% of cancers of the cervix plus a large percentage of other lower anogenital tract cancers.¹ This was meant to describe the prevention potential of the quadrivalent vaccine. The currently available Gardasil 9 targets the HPV types that account for 90% of cervical cancers,² with projected effectiveness likely to vary based on geographic variation in HPV subtypes, ranging from 86.5% in Australia to 92% in North America.³ It is difficult to precisely calculate the effectiveness of HPV vaccination alone, given that cervical cancer prevention is twofold, with primary vaccination and secondary screening (with several notable updates to US national screening guidelines during the same time frame as vaccine development).⁴

It is true that the 29% decrease in US cervical cancer incidence rates during the years 2011–2014 compared with 2003–2006 is less than the predicted 70%.⁵ However, not all eligible US females are vaccinated; according to reports from the US Centers for Disease Control and Prevention, 49% of adolescents were appropriately immunized against HPV in 2017, an increase over the rate of only 35% in 2014.⁶ Low vaccination rates undoubtedly negatively impact any benefits from herd immunity, though the exact benefits of this population immunity are difficult to quantify.⁷

In Australia, a national school-based HPV vaccination program was initiated in 2007, making the vaccine available for free. Over 70% of girls ages 12 and 13 were vaccinated, and follow-up within the same decade showed a greater than 90% reduction in genital warts, as well as a reduction in high-grade cervical lesions.⁸ In addition, the incidence of genital warts in unvaccinated heterosexual males during the prevaccination vs the vaccination period decreased by up to 81% (a marker of herd immunity).⁹

In the US, the HPV subtypes found in the quadrivalent vaccine decreased by 71% in those ages 14 to 19, within 8 years of vaccine introduction.¹⁰ An analysis of US state cancer registries between 2009 and 2012 showed that in Michigan, the rates of high-grade, precancerous lesions declined by 37% each year for women ages 15 to 19, thought to be due to changes in screening and vaccination guidelines.¹¹ Similarly, an analysis of 9 million privately insured US females showed that the presence of high-grade precancerous lesions significantly decreased between the years 2007 and 2014 in those ages 15 to 24 (vaccinated individuals), but not in those ages 25 to 39 (unvaccinated individuals).¹² Most recently, a study of 10,206 women showed a 21.9% decrease in cervical intraepithelial neoplasia grade 2 or worse lesions due to HPV subtypes 16 or 18 in those who have received at least 1 dose of the vaccine; reduced rates in unvaccinated women were also seen, representing first evidence of herd immunity in the United States.¹³ In contrast, the rates of high-grade lesions due to nonvaccine HPV subtypes remained constant. Given that progression to cervical cancer can take 10 to 15 years or longer after HPV infection, true vaccine benefits will emerge once increased vaccination rates are achieved and after at least a decade of follow-up.

We applaud Dr. Lichtenberg’s efforts to clarify vaccine efficacy for appropriate counseling, as this is key to ensuring patient trust. Immunization fears have fueled the re-emergence of vaccine-preventable illnesses across the world. Given the wave of vaccine misinformation on the Internet, we all face patients and family members skeptical of vaccine efficacy and safety. Those requesting more information deserve an honest, informed discussion with their provider. Interestingly, however, among 955 unvaccinated women, the belief of not being at risk for HPV was the most common reason for not receiving the vaccine.¹⁴ Effective education can be achieved by focusing on the personal risks of HPV to the patient, as well as the overall favorable risk vs benefits of vaccination. Quoting an exact rate of cancer reduction is likely a less effective counseling strategy, and these efficacy estimates will change as vaccination rates and HPV prevalence within the population change over time.