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The Effects of Human Papillomavirus Infection and Vaccination on Cardiovascular Diseases, NHANES 2003-2016

  • Xiaopeng Liang
    Footnotes
    Affiliations
    Division of Clinical Pharmacology and Therapeutics, Department of Medicine, School of Clinical Medicine, University of Hong Kong, Hong Kong, China
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  • Oscar Hou In Chou
    Footnotes
    Affiliations
    Division of Clinical Pharmacology and Therapeutics, Department of Medicine, School of Clinical Medicine, University of Hong Kong, Hong Kong, China
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  • Bernard M.Y. Cheung
    Correspondence
    Requests for reprints should be addressed to Bernard M. Y. Cheung, MB, BChir, PhD, Department of Medicine, School of Clinical Medicine, Queen Mary Hospital 102 Pokfulam Road, Hong Kong, China.
    Affiliations
    Division of Clinical Pharmacology and Therapeutics, Department of Medicine, School of Clinical Medicine, University of Hong Kong, Hong Kong, China

    State Key Laboratory of Pharmaceutical Biotechnology, University of Hong Kong, Pokfulam, Hong Kong, China

    Institute of Cardiovascular Science and Medicine, University of Hong Kong, Pokfulam, Hong Kong, China
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  • Author Footnotes
    1 Joint authors with equal contributions
Published:October 14, 2022DOI:https://doi.org/10.1016/j.amjmed.2022.09.021

      Abstract

      Background

      Human papillomavirus (HPV) infection has been proposed to be an unconventional risk factor for cardiovascular diseases. We investigated the association between HPV infection and cardiovascular diseases among women with or without HPV vaccination.

      Methods

      This cross-sectional study included 9,353 women aged between 20 to 59 years old who were tested for vaginal HPV DNA in the National Health and Nutrition Examination Survey (NHANES) 2003-2016. Cardiovascular diseases were defined as the presence of self-reported coronary heart diseases, heart attacks, angina pectoris, and stroke. The association between HPV and cardiovascular diseases was studied using logistic regression, with adjustment for the potential confounders.

      Results

      A total of 40.8% of women were HPV DNA positive; 3.0% had cardiovascular diseases; and 9.0% of women received the HPV vaccine. The presence of vaginal HPV infection was associated with cardiovascular diseases (odd ratio [OR] = 1.66, 95% confidence interval [CI] 1.28-2.16), which remained significant (OR = 1.54, 95% CI 1.15-2.08) after adjustment for sociodemographic characteristics, lifestyle behaviors, medical history, family history of cardiovascular diseases, and antihypertensive drugs. The association was absent among those who were vaccinated against HPV (OR= 0.50, 95% CI 0.07-3.51) but present among those who were not (OR = 1.63, 95% CI 1.18-2.25).

      Conclusions

      There was an association between HPV infection and cardiovascular diseases. This association was not significant among women vaccinated against HPV. The effect of HPV vaccination on cardiovascular diseases requires further investigation.

      Keywords

      Abbreviations:

      ACE (Angiotensin-converting enzyme), ARB (Angiotensin II receptor blocker), CI (Confidence intervals), HPV (Human papillomavirus), ITR (InflammoThrombotic Response), NHANES (National Health and Nutrition Examination Survey), OR (Odds ratio), SARS-CoV-2 (Severe acute respiratory syndrome coronavirus 2)
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      References

      1. Global, regional, and national age-sex specific mortality for 264 causes of death, 1980-2016: a systematic analysis for the Global Burden of Disease Study 2016.
        Lancet. 2017; 390: 1151-1210https://doi.org/10.1016/s0140-6736(17)32152-9
        • MacMahon S
        • Peto R
        • Cutler J
        • et al.
        Blood pressure, stroke, and coronary heart disease. Part 1, Prolonged differences in blood pressure: prospective observational studies corrected for the regression dilution bias.
        Lancet. 1990; 335: 765-774https://doi.org/10.1016/0140-6736(90)90878-9
        • Jagannathan R
        • Patel SA
        • Ali MK
        • Narayan KMV.
        Global updates on cardiovascular disease mortality trends and attribution of traditional risk factors.
        Curr Diab Rep. 2019; 19: 44https://doi.org/10.1007/s11892-019-1161-2
        • Cheung BM
        • Lauder IJ
        • Lau CP
        • Kumana CR.
        Meta-analysis of large randomized controlled trials to evaluate the impact of statins on cardiovascular outcomes.
        Br J Clin Pharmacol. 2004; 57: 640-651https://doi.org/10.1111/j.1365-2125.2003.02060.x
        • Ong KL
        • Tso AW
        • Lam KS
        • Cheung BM.
        Gender difference in blood pressure control and cardiovascular risk factors in Americans with diagnosed hypertension.
        Hypertension. 2008; 51: 1142-1148https://doi.org/10.1161/hypertensionaha.107.105205
        • Khot UN
        • Khot MB
        • Bajzer CT
        • et al.
        Prevalence of conventional risk factors in patients with coronary heart disease.
        JAMA. 2003; 290: 898-904https://doi.org/10.1001/jama.290.7.898
        • Fleming RM
        The pathogenesis of vascular disease.
        in: Chang JB Textbook of Angiology. Springer, New York, NY2000: 787-798
        • Fleming RM
        • Fleming MR
        FMTVDM quantitative nuclear imaging finds three treatments for SARS-CoV-2.
        Biomed J Sci & Tech Res. 2021; 33: 26041-26083https://doi.org/10.26717/BJSTR.2021.33.005443
        • Schiffman M
        • Castle PE
        • Jeronimo J
        • Rodriguez AC
        • Wacholder S.
        Human papillomavirus and cervical cancer.
        Lancet. 2007; 370: 890-907https://doi.org/10.1016/s0140-6736(07)61416-0
        • Shen Y
        • Xia J
        • Li H
        • Xu Y
        • Xu S.
        Human papillomavirus infection rate, distribution characteristics, and risk of age in pre- and postmenopausal women.
        BMC Womens Health. 2021; 21: 80https://doi.org/10.1186/s12905-021-01217-4
        • Kuo HK
        • Fujise K.
        Human papillomavirus and cardiovascular disease among U.S. women in the National Health and Nutrition Examination Survey, 2003 to 2006.
        J Am Coll Cardiol. 2011; 58: 2001-2006https://doi.org/10.1016/j.jacc.2011.07.038
        • Brito LMO
        • Brito HO
        • Corrêa R
        • et al.
        Human papillomavirus and coronary artery disease in climacteric women: is there an association?.
        ScientificWorldJournal. 2019; 1872536https://doi.org/10.1155/2019/1872536
        • Lawson JS
        • Glenn WK
        • Tran DD
        • Ngan CC
        • Duflou JA
        • Whitaker NJ.
        Identification of human papilloma viruses in atheromatous coronary artery disease.
        Front Cardiovasc Med. 2015; 2: 17https://doi.org/10.3389/fcvm.2015.00017
        • Lowy DR.
        HPV vaccination to prevent cervical cancer and other HPV-associated disease: from basic science to effective interventions.
        J Clin Invest. 2016; 126: 5-11https://doi.org/10.1172/jci85446
        • Hirth J.
        Disparities in HPV vaccination rates and HPV prevalence in the United States: a review of the literature.
        Hum Vaccin Immunother. 2019; 15: 146-155https://doi.org/10.1080/21645515.2018.1512453
        • Centers for Disease Control and Prevention (CDC)
        National Center for Health Statistics (NCHS). National Health and Nutrition Examination Survey Data.
        U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, Hyattsville, MD2016 (Availabe at:) (Accessed Nov 20, 2021)
        • Butler L
        • Popkin BM
        • Poti JM.
        Associations of alcoholic beverage consumption with dietary intake, waist circumference, and body mass index in US adults: National Health and Nutrition Examination Survey 2003-2012.
        J Acad Nutr Diet. 2018; 118: 409-420.e3https://doi.org/10.1016/j.jand.2017.09.030
        • Strath SJ
        • Kaminsky LA
        • Ainsworth BE
        • et al.
        Guide to the assessment of physical activity: clinical and research applications: a scientific statement from the American Heart Association.
        Circulation. 2013; 128: 2259-2279https://doi.org/10.1161/01.cir.0000435708.67487.da
        • National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III)
        Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report.
        Circulation. 2002; 106: 3143-3421
        • Whelton PK
        • Carey RM
        • Aronow WS
        • et al.
        2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: executive summary: a report of the American College of Cardiology/American Heart Association task force on clinical practice guidelines.
        Hypertension. 2018; 71: 1269-1324https://doi.org/10.1161/hyp.0000000000000066
      2. Centers for Disease Control and Prevention (CDC),National Center for Health Statistics (NCHS), National Health and Nutrition Examination Survey (NHANES). Laboratory procedure manual human papillomavirus (HPV) genotypes. Available at:https://wwwn.cdc.gov/nchs/data/nhanes/2015-2016/labmethods/HPVSWR_I_HPVS_I_R_MET.pdf. Accessed Nov 20, 2021.

        • Joo EJ
        • Chang Y
        • Kwon MJ
        • Cho A
        • Cheong HS
        • Ryu S.
        High-risk human papillomavirus infection and the risk of cardiovascular disease in Korean women.
        Circ Res. 2019; 124: 747-756https://doi.org/10.1161/circresaha.118.313779
        • Paavonen J
        • Jenkins D
        • Bosch FX
        • et al.
        Efficacy of a prophylactic adjuvanted bivalent L1 virus-like-particle vaccine against infection with human papillomavirus types 16 and 18 in young women: an interim analysis of a phase III double-blind, randomised controlled trial.
        Lancet. 2007; 369: 2161-2170https://doi.org/10.1016/s0140-6736(07)60946-5
        • Joura EA
        • Giuliano AR
        • Iversen OE
        • et al.
        A 9-valent HPV vaccine against infection and intraepithelial neoplasia in women.
        N Engl J Med. 2015; 372: 711-723https://doi.org/10.1056/NEJMoa1405044
        • Carozzi F
        • Puliti D
        • Ocello C
        • et al.
        Monitoring vaccine and non-vaccine HPV type prevalence in the post-vaccination era in women living in the Basilicata region, Italy.
        BMC Infect Dis. 2018; 18: 38https://doi.org/10.1186/s12879-018-2945-8
        • Paavonen J
        • Naud P
        • Salmerón J
        • et al.
        Efficacy of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine against cervical infection and precancer caused by oncogenic HPV types (PATRICIA): final analysis of a double-blind, randomised study in young women.
        Lancet. 2009; 374: 301-314https://doi.org/10.1016/s0140-6736(09)61248-4
        • Zhang Z
        • Zhang J
        • Xia N
        • Zhao Q.
        Expanded strain coverage for a highly successful public health tool: Prophylactic 9-valent human papillomavirus vaccine.
        Hum Vaccin Immunother. 2017; 13: 2280-2291https://doi.org/10.1080/21645515.2017.1346755
        • Avni-Singer LR
        • Yakely A
        • Sheth SS
        • Shapiro ED
        • Niccolai LM
        • Oliveira CR.
        Assessing sociodemographic differences in human papillomavirus vaccine impact studies in the United States: a systematic review using narrative synthesis.
        Public Health. 2020; 178: 137-150https://doi.org/10.1016/j.puhe.2019.08.010
        • Markowitz LE
        • Liu G
        • Hariri S
        • Steinau M
        • Dunne EF
        • Unger ER.
        Prevalence of HPV after introduction of the vaccination program in the United States.
        Pediatrics. 2016; 137e20151968https://doi.org/10.1542/peds.2015-1968
        • Rosenblum HG
        • Lewis RM
        • Gargano JW
        • Querec TD
        • Unger ER
        • Markowitz LE.
        Declines in prevalence of human papillomavirus vaccine-type infection among females after introduction of vaccine - United States, 2003-2018.
        MMWR Morb Mortal Wkly Rep. 2021; 70: 415-420https://doi.org/10.15585/mmwr.mm7012a2
        • Füle T
        • Máthé M
        • Suba Z
        • et al.
        The presence of human papillomavirus 16 in neural structures and vascular endothelial cells.
        Virology. 2006; 348: 289-296https://doi.org/10.1016/j.virol.2005.12.043
        • Foresta C
        • Bertoldo A
        • Garolla A
        • et al.
        Human papillomavirus proteins are found in peripheral blood and semen Cd20+ and Cd56+ cells during HPV-16 semen infection.
        BMC Infect Dis. 2013; 13: 593https://doi.org/10.1186/1471-2334-13-593
        • Ross R.
        Atherosclerosis is an inflammatory disease.
        Am Heart J. 1999; 138: S419-S420https://doi.org/10.1016/s0002-8703(99)70266-8
        • Kovacic MB
        • Katki HA
        • Kreimer AR
        • Sherman ME.
        Epidemiologic analysis of histologic cervical inflammation: relationship to human papillomavirus infections.
        Hum Pathol. 2008; 39: 1088-1095https://doi.org/10.1016/j.humpath.2007.12.002
        • Bonin LR
        • Madden K
        • Shera K
        • et al.
        Generation and characterization of human smooth muscle cell lines derived from atherosclerotic plaque.
        Arterioscler Thromb Vasc Biol. 1999; 19: 575-587https://doi.org/10.1161/01.atv.19.3.575
        • Federico A
        • Morgillo F
        • Tuccillo C
        • Ciardiello F
        • Loguercio C.
        Chronic inflammation and oxidative stress in human carcinogenesis.
        Int J Cancer. 2007; 121: 2381-2386https://doi.org/10.1002/ijc.23192
        • Arbyn M
        • Verdoodt F
        • Snijders PJ
        • et al.
        Accuracy of human papillomavirus testing on self-collected versus clinician-collected samples: a meta-analysis.
        Lancet Oncol. 2014; 15: 172-183https://doi.org/10.1016/s1470-2045(13)70570-9