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burden and trends in human papillomavirus (HPV)-associated cancers and HPV vaccination coverage levels and RE: inequalities in human papillomavirus (HPV)-associated cancers: implications for the success of HPV vaccination. J Natl Cancer Inst 2013; 105:749–50. Centers for Disease Control and Prevention (CDC). National and state vaccination coverage among adolescents aged 13–17 years— United States. 2011. MMWR 2012; 34:671–7. Dunne EF, Unger ER, Sternberg M, et al. Prevalence of HPV infection among females in the United States. JAMA 2007; 297:813–9. Dobson SR, McNeil S, Dionne M, et al. Immunogenicity of 2 doses of HPV vaccine in younger adolescents vs 3 doses in young women: a randomized clinical trial. JAMA 2013; 309:1793–802. Harper DM, Vierthaler SL, Santee JA. Review of gardasil. J Vaccines Vaccin 2010; 1. doi:pii: 1000107. Forman D, de Martel C, Lacey CJ, et al. Global burden of human papillomavirus and related diseases. Vaccine 2012; 30(Suppl 5): F12–23.
Received 2 July 2013; accepted 16 December 2013; electronically published 23 December 2013. This work has not been presented at a conference. Correspondence: Diane M Harper, MD, MPH, MS, Professor and Chair, University of Louisville School of Medicine, 501 East Broadway, Louisville, KY 40202 (diane.harper@louisville. edu). The Journal of Infectious Diseases 2014;209:1302–4 © The Author 2013. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.
[email protected]. DOI: 10.1093/infdis/jit836
Previous History and Cigarette Smoking as Interfering Factors for the Effect of Vaccine on Human Papillomavirus Infection TO THE EDITOR—We have read with great interest the news and views in the article “Reduction in Human Papillomavirus (HPV) Prevalence Among Young Women Following HPV Vaccine Introduction in the United States, National Health and Nutrition Examination Surveys, 2003– 2010” [1]. This article pointed out a remarkable reduction in the prevalence of human papillomavirus (HPV) due to HPV vaccine introduction. However, it is unclear why the vaccine only protected female subjects aged 14–19 years but failed to bring benefit to subjects with older ages. As is stated in the article, most Americans are infected with HPV in their 1304
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late teens and early twenties. Unfortunately, the HPV infection status of each interviewed subject was not screened before the vaccine introduction; thus we cannot exclude the possibility that the nonsignificant protection in females more than 20 years old results from a preexisting history of HPV infection. Furthermore, it is well known that nicotine (a major component of cigarette smoking) exerts strong suppressive effects on the immune system and increases the risk of various virus infections [2]. Substantial evidences have demonstrated the ability of nicotine to increase virus infection rate via enhancing the proliferation of cancer cells or stem cells [3, 4]. In addition, cigarette smoking has been linked to increased HPV DNA load [5], a strong indicator of higher risk of cervical cancer [6]. Therefore, it is important to investigate whether the observed discrepancy in vaccine efficacy among groups with different ages is associated with specific behaviors, such as cigarette smoking. Though the report of HPV vaccine has revealed encouraging result for teenagers, to confirm the conclusion and more importantly to guarantee a better protection, the previous history of HPV infection and cigarette smoking, as well as other interfering factors, should be included into the interview questionnaire and statistical analysis. Notes Financial support. This work was supported by the National Basic Research Program (973 Program; grant 9732013CB531200) and Chinese National Science Funds (grants 81070676 and 81170186). Potential conflicts of interest. All authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.
Haifeng Pei,1 Qiujun Yu,1 Qiang Xue,1 Feipeng Wei,2 and Ling Tao1 1
Department of Cardiology, Xijing Hospital, and 2 Department of Interventional Radiology, Tangdu Hospital, Fourth Military Medical University, Xi’an, China
CORRESPONDENCE
References 1. Markowitz LE, Hariri S, Lin C, et al. Reduction in human papillomavirus (HPV) prevalence among young women following HPV vaccine introduction in the United States, National Health and Nutrition Examination Surveys, 2003–2010. J Infect Dis 2013; 208:385–93. 2. Sopori M. Effects of cigarette smoke on the immune system. Nat Rev Immunol 2002; 2: 372–7. 3. Roman J, Koval M. Control of lung epithelial growth by a nicotinic acetylcholine receptor: the other side of the coin. Am J Pathol 2009; 175:1799–801. 4. Yu J, Huang NF, Wilson KD, et al. nAChRs mediate human embryonic stem cell-derived endothelial cells: proliferation, apoptosis, and angiogenesis. PLoS One 2009; 4:e7040. 5. Xi LF, Koutsky LA, Castle PE, et al. Relationship between cigarette smoking and human papilloma virus types 16 and 18 DNA load. Cancer Epidemiol Biomarkers Prev 2009; 18: 3490–6. 6. Cigarette smoking linked to increased human papillomavirus DNA load. CA Cancer J Clin 2010; 60:137–8. Received 13 November 2013; accepted 16 December 2013; electronically published 23 December 2013. Correspondence: Ling Tao, MD, PhD, Professor and Vice Chief, Department of Cardiology, Xijing Hospital, Fourth Military Medical University, 15 Changlexi Rd, Xi’an 710032, China (
[email protected]) The Journal of Infectious Diseases 2014;209:1304 © The Author 2013. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.
[email protected]. DOI: 10.1093/infdis/jit837
Reply to Groner et al and Pei et al TO THE EDITOR—The comments from Groner and colleagues relating to human papillomavirus (HPV) DNA prevalence among 14–19 year olds in the prevaccine and vaccine eras [1] reflect their profound misunderstanding of the data that we would like to correct. Prevaccine era HPV data from the National Health and Nutrition Examination Surveys (NHANES) 2003–2004 were first published based on a less sensitive HPV assay than the one we currently use [2]. We subsequently documented the impact of an assay change [3] and published updated data on HPV prevalence from NHANES 2003– 2006 in order to be able to monitor HPV prevalence trends [4]. The data in our recent article, showing a decline in vaccine type HPV prevalence after vaccine
introduction, were based on comparisons using the same assay in prevaccine (2003– 2006) and vaccine (2007–2010) eras [1]. We agree with Groner et al that changes in sexual behavior could certainly impact our HPV prevalence determinations, and we clearly stated this in our article. We did not detect differences in sexual behavior among 14–19 year olds between NHANES 2003–2006 and 2007–2010; however, limited sexual behavior data were collected. Groner et al reference data from other studies on adolescent sexual behavior that show changes over a longer time period. However, data from the Youth Risk Behavior Surveillance System (YRBS; cited by Groner et al) are consistent with the behavior data we reported from NHANES: they show no significant decrease in the percent of youth ever having had sexual intercourse during the time period of our study [5]. YRBS also found no increase in condom use during those years. Groner and colleagues also question our discussion of herd effects as a possible explanation of the larger than expected declines in HPV vaccine type prevalence. Although they are correct that some modeling studies suggest greater herd immunity with male compared to female HPV vaccination, it should be noted that models indicate herd immunity can be anticipated with female vaccination. Indeed, published data from country experiences postvaccine introduction suggest herd effects from female vaccination [6]. In Australia, where high HPV vaccination coverage was achieved among females in the target age as well as catch-up age groups, a decline in genital wart diagnoses was observed among both females and heterosexual males, although only females were targeted by the vaccination program. Groner et al misinterpret our discussion of the potential effectiveness from less than a full 3-dose schedule as one of several possible explanations for the larger than expected decrease in prevalence observed. Far from a celebration, our discussion points out the importance of monitoring and reviewing data that
suggest that HPV vaccine schedules with less than 3 doses might have high efficacy. It is correct that most of these data come from immunogenicity studies comparing 2-dose with 3-dose schedules [7, 8]. Of note, noninferiority of antibody titers has been used to support some HPV vaccine indications. Although there is no antibody threshold that has been established for protection, immunity provided by prophylactic vaccination is antibody mediated. Future studies will provide more information on reduced dose HPV vaccine schedules. Groner and colleagues site concerns about failure to detect HPV 18 antibodies in a subset of those vaccinated in the quadrivalent HPV vaccine clinical trials, but they fail to note that no breakthrough HPV 18 infection or disease has been detected in those trials. The latter point supports the suggestion that a level of antibody below that detectable by the serologic assay used in the trial is protective [9]. The small number of HPV 18 infections in our study prevents conclusions about that individual type. Pei and colleagues suggest that the impact of smoking may be one reason why we did not observe a decrease in vaccine type HPV prevalence among 20– 29-year-old women. Although smoking has been associated with increased risk of HPV persistent infection, we believe the more likely explanation is the lower vaccine coverage in this age group early in the vaccine era, and the fact that women in this age group who received vaccine were likely to have been vaccinated after onset of sexual activity. Vaccine effectiveness would be lower in these individuals. In the coming years, we can investigate whether there is a decrease in prevalence among 20–29 year-olds, as women who were vaccinated when they were younger age into this age group. Note Potential conflicts of interest. All authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.
Lauri E. Markowitz,1 Susan Hariri,1 Eileen F. Dunne,1 Martin Steinau,2 and Elizabeth R. Unger2 1
Division of STD Prevention, National Center for HIV/ AIDS, Viral Hepatitis, STD, and TB Prevention; and 2 Division of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia References 1. Markowitz LE, Hariri S, Lin C, et al. Reduction in human papillomavirus (HPV) prevalence among young women following HPV vaccine introduction in the United States, National Health and Nutrition Examination Surveys, 2003–2010. J Infect Dis 2013; 208:385–93. 2. Dunne EF, Unger ER, Sternberg M, et al. Prevalence of HPV infection among females in the United States. JAMA 2007; 297: 813–9. 3. Unger ER, Steinau M, Lin JM, Patel SS, Swan DC. Impact of HPV assay on observed population prevalence. Diagn Mol Path 2011; 20:101–4. 4. Hariri S, Unger ER, Sternberg M, et al. Prevalence of genital human papillomavirus among females in the United States, the National Health and Nutrition Examination Survey, 2003–2006. J Infect Dis 2011; 204: 566–73. 5. Centers for Disease Control and Prevention. Trends in HIV-related risk behaviors among high school students—United States, 1991– 2011. MMWR 2012; 61:556–60. 6. Ali H, Donovan B, Wand H, et al. Genital warts in young Australians five years into national human papillomavirus vaccination programme: national surveillance data. BMJ 2013; 346:f2032. 7. Romanowski B, Schwarz TF, Ferguson LM, et al. Immunogenicity and safety ofthe HPV16/18 AS04-adjuvanted vaccine administered as a 2-dose schedule compared with the licensed 3-dose schedule: results from a randomized study. Hum Vaccin 2011; 7: 1374–86. 8. Dobson SR, McNeil S, Dionne M, et al. Immunogenicity of 2 doses of HPV vaccine in younger adolescents vs 3 doses in young women: a randomized clinical trial. JAMA 2013; 309:1793–802. 9. Schiller JT, Castellsague X, Garland SM. A review of clinical trials of human papillomavirus prophylactic vaccines. Vaccine 2012; 30(Suppl 5):F123–38. Received 16 December 2013; accepted 16 December 2013; electronically published 23 December 2013. Correspondence: Lauri E. Markowitz, MD, Centers for Disease Control and Prevention, 1600 Clifton Rd, Atlanta, GA 30333 (
[email protected]). The Journal of Infectious Diseases 2014;209:1304–5 Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2013. This work is written by (a) US Government employee(s) and is in the public domain in the US. DOI: 10.1093/infdis/jit835
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