• 1.

    Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A, 2018. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 68: 394424.

    • Search Google Scholar
    • Export Citation
  • 2.

    Lemp JM et al., 2020. Lifetime prevalence of cervical cancer screening in 55 low- and middle-income countries. JAMA 324: 15321542.

  • 3.

    Peto J, Gilham C, Fletcher O, Matthews FE, 2004. The cervical cancer epidemic that screening has prevented in the UK. Lancet 364: 249256.

  • 4.

    Bruni L, Diaz M, Castellsague X, Ferrer E, Bosch FX, de Sanjose S, 2010. Cervical human papillomavirus prevalence in 5 continents: meta-analysis of 1 million women with normal cytological findings. J Infect Dis 202: 17891799.

    • Search Google Scholar
    • Export Citation
  • 5.

    Maucort-Boulch D, Franceschi S, Plummer M, Group IHPSS, 2008. International correlation between human papillomavirus prevalence and cervical cancer incidence. Cancer Epidemiol Biomarkers Prev 17: 717720.

    • Search Google Scholar
    • Export Citation
  • 6.

    Gravitt PE et al., 2016. Soil-transmitted helminth infections are associated with an increase in human papillomavirus prevalence and a T-Helper Type 2 cytokine signature in cervical fluids. J Infect Dis 213: 723730.

    • Search Google Scholar
    • Export Citation
  • 7.

    Walboomers JM, Jacobs MV, Manos MM, Bosch FX, Kummer JA, Shah KV, Snijders PJ, Peto J, Meijer CJ, Munoz N, 1999. Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol 189: 1219.

    • Search Google Scholar
    • Export Citation
  • 8.

    Munoz N, Bosch FX, de Sanjose S, Herrero R, Castellsague X, Shah KV, Snijders PJ, Meijer CJ, International Agency for Research on Cancer Multicenter Cervical Cancer Study G , 2003. Epidemiologic classification of human papillomavirus types associated with cervical cancer. N Engl J Med 348: 518527.

    • Search Google Scholar
    • Export Citation
  • 9.

    Moscicki AB, 2005. Human papilloma virus, papanicolaou smears, and the college female. Pediatr Clin North Am 52: 163177, ix.

  • 10.

    Burchell AN, Winer RL, de Sanjose S, Franco EL, 2006. Chapter 6: epidemiology and transmission dynamics of genital HPV infection. Vaccine 24 (Suppl 3 ):S3/5261.

    • Search Google Scholar
    • Export Citation
  • 11.

    Schiffman M, Kjaer SK, 2003. Chapter 2: natural history of anogenital human papillomavirus infection and neoplasia. J Natl Cancer Inst Monogr 31: 1419.

    • Search Google Scholar
    • Export Citation
  • 12.

    Plummer M, Schiffman M, Castle PE, Maucort-Boulch D, Wheeler CM, Group A, 2007. A 2-year prospective study of human papillomavirus persistence among women with a cytological diagnosis of atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesion. J Infect Dis 195: 15821589.

    • Search Google Scholar
    • Export Citation
  • 13.

    Rosa MI, Fachel JM, Rosa DD, Medeiros LR, Igansi CN, Bozzetti MC, 2008. Persistence and clearance of human papillomavirus infection: a prospective cohort study. Am J Obstet Gynecol 199: 617 e17.

    • Search Google Scholar
    • Export Citation
  • 14.

    Bosch FX, Lorincz A, Munoz N, Meijer CJ, Shah KV, 2002. The causal relation between human papillomavirus and cervical cancer. J Clin Pathol 55: 244265.

    • Search Google Scholar
    • Export Citation
  • 15.

    Doorbar J, 2018. Host control of human papillomavirus infection and disease. Best Pract Res Clin Obstet Gynaecol 47: 2741.

  • 16.

    Hammer A, de Koning MN, Blaakaer J, Steiniche T, Doorbar J, Griffin H, Mejlgaard E, Svanholm H, Quint WG, Gravitt PE, 2019. Whole tissue cervical mapping of HPV infection: molecular evidence for focal latent HPV infection in humans. Papillomavirus Res 7: 8287.

    • Search Google Scholar
    • Export Citation
  • 17.

    Leonard SM, Pereira M, Roberts S, Cuschieri K, Nuovo G, Athavale R, Young L, Ganesan R, Woodman CB, 2016. Evidence of disrupted high-risk human papillomavirus DNA in morphologically normal cervices of older women. Sci Rep 6: 20847.

    • Search Google Scholar
    • Export Citation
  • 18.

    Gravitt PE, Winer RL, 2017. Natural history of HPV infection across the lifespan: role of viral latency. Viruses 9: 267.

  • 19.

    Fu TC et al., 2016. Re-detection vs. new acquisition of high-risk human papillomavirus in mid-adult women. Int J Cancer 139: 22012212.

  • 20.

    Paul P, Hammer A, Rositch AF, Burke AE, Viscidi RP, Silver MI, Campos N, Youk AO, Gravitt PE, 2021. Rates of new human papillomavirus detection and loss of detection in middle-aged women by recent and past sexual behavior. J Infect Dis 223: 14231432.

    • Search Google Scholar
    • Export Citation
  • 21.

    Rositch AF, Patel EU, Petersen MR, Quinn TC, Gravitt PE, Tobian AAR, 2021. Importance of lifetime sexual history on the prevalence of genital human papillomavirus among unvaccinated adults in NHANES: implications for adult HPV vaccination. Clin Infect Dis 72: e272e279.

    • Search Google Scholar
    • Export Citation
  • 22.

    Hammer A et al., 2020. A study of the risks of CIN3+ detection after multiple rounds of HPV testing: results of the 15-year cervical cancer screening experience at Kaiser Permanente northern California. Int J Cancer 147: 16121620.

    • Search Google Scholar
    • Export Citation
  • 23.

    Miranda PM, Silva NN, Pitol BC, Silva ID, Lima-Filho JL, Carvalho RF, Stocco RC, Becak W, Lima AA, 2013. Persistence or clearance of human papillomavirus infections in women in Ouro Preto, Brazil. BioMed Res Int 2013: 578276.

    • Search Google Scholar
    • Export Citation
  • 24.

    Schiffman M, Castle PE, Jeronimo J, Rodriguez AC, Wacholder S, 2007. Human papillomavirus and cervical cancer. Lancet 370: 890907.

  • 25.

    Fairley CK et al., 1994. Prevalence of HPV DNA in cervical specimens in women with renal transplants: a comparison with dialysis-dependent patients and patients with renal impairment. Nephrol Dial Transplant 9: 416420.

    • Search Google Scholar
    • Export Citation
  • 26.

    Ozsaran AA, Ates T, Dikmen Y, Zeytinoglu A, Terek C, Erhan Y, Ozacar T, Bilgic A, 1999. Evaluation of the risk of cervical intraepithelial neoplasia and human papilloma virus infection in renal transplant patients receiving immunosuppressive therapy. Eur J Gynaecol Oncol 20: 127130.

    • Search Google Scholar
    • Export Citation
  • 27.

    Critchlow CW, Hawes SE, Kuypers JM, Goldbaum GM, Holmes KK, Surawicz CM, Kiviat NB, 1998. Effect of HIV infection on the natural history of anal human papillomavirus infection. AIDS 12: 11771184.

    • Search Google Scholar
    • Export Citation
  • 28.

    Palefsky JM, Gonzales J, Greenblatt RM, Ahn DK, Hollander H, 1990. Anal intraepithelial neoplasia and anal papillomavirus infection among homosexual males with group IV HIV disease. JAMA 263: 29112916.

    • Search Google Scholar
    • Export Citation
  • 29.

    Palefsky JM, Minkoff H, Kalish LA, Levine A, Sacks HS, Garcia P, Young M, Melnick S, Miotti P, Burk R, 1999. Cervicovaginal human papillomavirus infection in human immunodeficiency virus-1 (HIV)-positive and high-risk HIV-negative women. J Natl Cancer Inst 91: 226236.

    • Search Google Scholar
    • Export Citation
  • 30.

    Luque AE, Demeter LM, Reichman RC, 1999. Association of human papillomavirus infection and disease with magnitude of human immunodeficiency virus type 1 (HIV-1) RNA plasma level among women with HIV-1 infection. J Infect Dis 179: 14051409.

    • Search Google Scholar
    • Export Citation
  • 31.

    Eckert LO, Watts DH, Koutsky LA, Hawes SE, Stevens CE, Kuypers J, Kiviat NB, 1999. A matched prospective study of human immunodeficiency virus serostatus, human papillomavirus DNA, and cervical lesions detected by cytology and colposcopy. Infect Dis Obstet Gynecol 7: 158164.

    • Search Google Scholar
    • Export Citation
  • 32.

    Minkoff H, Feldman J, DeHovitz J, Landesman S, Burk R, 1998. A longitudinal study of human papillomavirus carriage in human immunodeficiency virus-infected and human immunodeficiency virus-uninfected women. Am J Obstet Gynecol 178: 982986.

    • Search Google Scholar
    • Export Citation
  • 33.

    Sun XW, Kuhn L, Ellerbrock TV, Chiasson MA, Bush TJ, Wright TC Jr., 1997. Human papillomavirus infection in women infected with the human immunodeficiency virus. N Engl J Med 337: 13431349.

    • Search Google Scholar
    • Export Citation
  • 34.

    Moscicki AB, Ellenberg JH, Vermund SH, Holland CA, Darragh T, Crowley-Nowick PA, Levin L, Wilson CM, 2000. Prevalence of and risks for cervical human papillomavirus infection and squamous intraepithelial lesions in adolescent girls: impact of infection with human immunodeficiency virus. Arch Pediatr Adolesc Med 154: 127134.

    • Search Google Scholar
    • Export Citation
  • 35.

    Vernon SD, Unger ER, Piper MA, Severin ST, Wiktor SZ, Ghys PD, Miller DL, Horowitz IR, Greenberg AE, Reeves WC, 1999. HIV and human papillomavirus as independent risk factors for cervical neoplasia in women with high or low numbers of sex partners. Sex Transm Infect 75: 258260.

    • Search Google Scholar
    • Export Citation
  • 36.

    Scott M, Nakagawa M, Moscicki AB, 2001. Cell-mediated immune response to human papillomavirus infection. Clin Diagn Lab Immunol 8: 209220.

  • 37.

    Malejczyk J, Malejczyk M, Kock A, Urbanski A, Majewski S, Hunzelmann N, Jablonska S, Orth G, Luger TA, 1992. Autocrine growth limitation of human papillomavirus type 16-harboring keratinocytes by constitutively released tumor necrosis factor-alpha. J Immunol 149: 27022708.

    • Search Google Scholar
    • Export Citation
  • 38.

    Woodworth CD, Notario V, DiPaolo JA, 1990. Transforming growth factors beta 1 and 2 transcriptionally regulate human papillomavirus (HPV) type 16 early gene expression in HPV-immortalized human genital epithelial cells. J Virol 64: 47674775.

    • Search Google Scholar
    • Export Citation
  • 39.

    Khan MA, Tolleson WH, Gangemi JD, Pirisi L, 1993. Inhibition of growth, transformation, and expression of human papillomavirus type 16 E7 in human keratinocytes by alpha interferons. J Virol 67: 33963403.

    • Search Google Scholar
    • Export Citation
  • 40.

    Kyo S, Inoue M, Hayasaka N, Inoue T, Yutsudo M, Tanizawa O, Hakura A, 1994. Regulation of early gene expression of human papillomavirus type 16 by inflammatory cytokines. Virology 200: 130139.

    • Search Google Scholar
    • Export Citation
  • 41.

    Scott M, Stites DP, Moscicki AB, 1999. Th1 cytokine patterns in cervical human papillomavirus infection. Clin Diagn Lab Immunol 6: 751755.

  • 42.

    Shannon B et al., 2017. Association of HPV infection and clearance with cervicovaginal immunology and the vaginal microbiota. Mucosal Immunol 10: 13101319.

    • Search Google Scholar
    • Export Citation
  • 43.

    Pao CC, Lin CY, Yao DS, Tseng CJ, 1995. Differential expression of cytokine genes in cervical cancer tissues. Biochem Biophys Res Commun 214: 11461151.

    • Search Google Scholar
    • Export Citation
  • 44.

    al-Saleh W, Giannini SL, Jacobs N, Moutschen M, Doyen J, Boniver J, Delvenne P, 1998. Correlation of T-helper secretory differentiation and types of antigen-presenting cells in squamous intraepithelial lesions of the uterine cervix. J Pathol 184: 283290.

    • Search Google Scholar
    • Export Citation
  • 45.

    Peghini BC, Abdalla DR, Barcelos AC, Teodoro L, Murta EF, Michelin MA, 2012. Local cytokine profiles of patients with cervical intraepithelial and invasive neoplasia. Hum Immunol 73: 920926.

    • Search Google Scholar
    • Export Citation
  • 46.

    Clerici M, Merola M, Ferrario E, Trabattoni D, Villa ML, Stefanon B, Venzon DJ, Shearer GM, De Palo G, Clerici E, 1997. Cytokine production patterns in cervical intraepithelial neoplasia: association with human papillomavirus infection. J Natl Cancer Inst 89: 245250.

    • Search Google Scholar
    • Export Citation
  • 47.

    Tsukui T et al., 1996. Interleukin 2 production in vitro by peripheral lymphocytes in response to human papillomavirus-derived peptides: correlation with cervical pathology. Cancer Res 56: 39673974.

    • Search Google Scholar
    • Export Citation
  • 48.

    Hotez PJ, Brindley PJ, Bethony JM, King CH, Pearce EJ, Jacobson J, 2008. Helminth infections: the great neglected tropical diseases. J Clin Invest 118: 13111321.

    • Search Google Scholar
    • Export Citation
  • 49.

    Maizels RM, Gomez-Escobar N, Gregory WF, Murray J, Zang X, 2001. Immune evasion genes from filarial nematodes. Int J Parasitol 31: 889898.

  • 50.

    Gazzinelli-Guimaraes PH, Nutman TB, 2018. Helminth parasites and immune regulation. F1000 Res 7: 1685.

  • 51.

    de Ruiter K et al., 2020. Helminth infections drive heterogeneity in human type 2 and regulatory cells. Sci Transl Med 12: eaaw3703.

  • 52.

    Maizels RM, Pearce EJ, Artis D, Yazdanbakhsh M, Wynn TA, 2009. Regulation of pathogenesis and immunity in helminth infections. J Exp Med 206: 20592066.

    • Search Google Scholar
    • Export Citation
  • 53.

    Cortes A, Munoz-Antoli C, Esteban JG, Toledo R, 2017. Th2 and Th1 responses: clear and hidden sides of immunity against intestinal helminths. Trends Parasitol 33: 678693.

    • Search Google Scholar
    • Export Citation
  • 54.

    Nogueira DS et al., 2016. Multiple exposures to ascaris suum induce tissue injury and mixed Th2/Th17 immune response in mice. PLoS Negl Trop Dis 10: e0004382.

    • Search Google Scholar
    • Export Citation
  • 55.

    Grencis RK, Worthington JJ, 2016. Tuft cells: a new flavor in innate epithelial immunity. Trends Parasitol 32: 583585.

  • 56.

    Elliott DE, Weinstock JV, 2012. Helminth-host immunological interactions: prevention and control of immune-mediated diseases. Ann N Y Acad Sci 1247: 8396.

    • Search Google Scholar
    • Export Citation
  • 57.

    Grainger JR et al., 2010. Helminth secretions induce de novo T cell Foxp3 expression and regulatory function through the TGF-beta pathway. J Exp Med 207: 23312341.

    • Search Google Scholar
    • Export Citation
  • 58.

    Sakaguchi S, Miyara M, Costantino CM, Hafler DA, 2010. FOXP3+ regulatory T cells in the human immune system. Nat Rev Immunol 10: 490500.

  • 59.

    Blankenhaus B, Klemm U, Eschbach ML, Sparwasser T, Huehn J, Kuhl AA, Loddenkemper C, Jacobs T, Breloer M, 2011. Strongyloides ratti infection induces expansion of Foxp3+ regulatory T cells that interfere with immune response and parasite clearance in BALB/c mice. J Immunol 186: 42954305.

    • Search Google Scholar
    • Export Citation
  • 60.

    Sawant DV, Gravano DM, Vogel P, Giacomin P, Artis D, Vignali DA, 2014. Regulatory T cells limit induction of protective immunity and promote immune pathology following intestinal helminth infection. J Immunol 192: 29042912.

    • Search Google Scholar
    • Export Citation
  • 61.

    Smith KA, Filbey KJ, Reynolds LA, Hewitson JP, Harcus Y, Boon L, Sparwasser T, Hammerling G, Maizels RM, 2016. Low-level regulatory T-cell activity is essential for functional type-2 effector immunity to expel gastrointestinal helminths. Mucosal Immunol 9: 428443.

    • Search Google Scholar
    • Export Citation
  • 62.

    Grencis RK, Entwistle GM, 1997. Production of an interferon-gamma homologue by an intestinal nematode: functionally significant or interesting artefact? Parasitology 115 (Suppl ):S101S106.

    • Search Google Scholar
    • Export Citation
  • 63.

    Smith P, Mangan NE, Walsh CM, Fallon RE, McKenzie AN, van Rooijen N, Fallon PG, 2007. Infection with a helminth parasite prevents experimental colitis via a macrophage-mediated mechanism. J Immunol 178: 45574566.

    • Search Google Scholar
    • Export Citation
  • 64.

    Piessens WF, McGreevy PB, Piessens PW, McGreevy M, Koiman I, Saroso JS, Dennis DT, 1980. Immune responses in human infections with Brugia malayi: specific cellular unresponsiveness to filarial antigens. J Clin Invest 65: 172179.

    • Search Google Scholar
    • Export Citation
  • 65.

    King CL, Kumaraswami V, Poindexter RW, Kumari S, Jayaraman K, Alling DW, Ottesen EA, Nutman TB, 1992. Immunologic tolerance in lymphatic filariasis. Diminished parasite-specific T and B lymphocyte precursor frequency in the microfilaremic state. J Clin Invest 89: 14031410.

    • Search Google Scholar
    • Export Citation
  • 66.

    King CL, Mahanty S, Kumaraswami V, Abrams JS, Regunathan J, Jayaraman K, Ottesen EA, Nutman TB, 1993. Cytokine control of parasite-specific anergy in human lymphatic filariasis. Preferential induction of a regulatory T helper type 2 lymphocyte subset. J Clin Invest 92: 16671673.

    • Search Google Scholar
    • Export Citation
  • 67.

    Yazdanbakhsh M, Paxton WA, Kruize YC, Sartono E, Kurniawan A, van het A, Selkirk ME, Partono F, Maizels RM, 1993. T cell responsiveness correlates differentially with antibody isotype levels in clinical and asymptomatic filariasis. J Infect Dis 167: 925931.

    • Search Google Scholar
    • Export Citation
  • 68.

    Sartono E, Kruize YC, Kurniawan A, van der Meide PH, Partono F, Maizels RM, Yazdanbakhsh M, 1995. Elevated cellular immune responses and interferon-gamma release after long-term diethylcarbamazine treatment of patients with human lymphatic filariasis. J Infect Dis 171: 16831687.

    • Search Google Scholar
    • Export Citation
  • 69.

    Harnett W, Harnett MM, 2008. Lymphocyte hyporesponsiveness during filarial nematode infection. Parasite Immunol 30: 447453.

  • 70.

    Babu S, Nutman TB, 2014. Immunology of lymphatic filariasis. Parasite Immunol 36: 338346.

  • 71.

    Mahanty S, Mollis SN, Ravichandran M, Abrams JS, Kumaraswami V, Jayaraman K, Ottesen EA, Nutman TB, 1996. High levels of spontaneous and parasite antigen-driven interleukin-10 production are associated with antigen-specific hyporesponsiveness in human lymphatic filariasis. J Infect Dis 173: 769773.

    • Search Google Scholar
    • Export Citation
  • 72.

    Mahanty S, Ravichandran M, Raman U, Jayaraman K, Kumaraswami V, Nutman TB, 1997. Regulation of parasite antigen-driven immune responses by interleukin-10 (IL-10) and IL-12 in lymphatic filariasis. Infect Immun 65: 17421747.

    • Search Google Scholar
    • Export Citation
  • 73.

    Cooper PJ, Mancero T, Espinel M, Sandoval C, Lovato R, Guderian RH, Nutman TB, 2001. Early human infection with Onchocerca volvulus is associated with an enhanced parasite-specific cellular immune response. J Infect Dis 183: 16621668.

    • Search Google Scholar
    • Export Citation
  • 74.

    Doetze A, Satoguina J, Burchard G, Rau T, Loliger C, Fleischer B, Hoerauf A, 2000. Antigen-specific cellular hyporesponsiveness in a chronic human helminth infection is mediated by T(h)3/T(r)1-type cytokines IL-10 and transforming growth factor-beta but not by a T(h)1 to T(h)2 shift. Int Immunol 12: 623630.

    • Search Google Scholar
    • Export Citation
  • 75.

    Metenou S, Nutman TB, 2013. Regulatory T cell subsets in filarial infection and their function. Front Immunol 4: 305.

  • 76.

    Wammes LJ, Hamid F, Wiria AE, Wibowo H, Sartono E, Maizels RM, Smits HH, Supali T, Yazdanbakhsh M, 2012. Regulatory T cells in human lymphatic filariasis: stronger functional activity in microfilaremics. PLoS Negl Trop Dis 6: e1655.

    • Search Google Scholar
    • Export Citation
  • 77.

    Gomez-Escobar N, Lewis E, Maizels RM, 1998. A novel member of the transforming growth factor-beta (TGF-beta) superfamily from the filarial nematodes Brugia malayi and B. pahangi. Exp Parasitol 88: 200209.

    • Search Google Scholar
    • Export Citation
  • 78.

    Satoguina J, Mempel M, Larbi J, Badusche M, Loliger C, Adjei O, Gachelin G, Fleischer B, Hoerauf A, 2002. Antigen-specific T regulatory-1 cells are associated with immunosuppression in a chronic helminth infection (onchocerciasis). Microbes Infect 4: 12911300.

    • Search Google Scholar
    • Export Citation
  • 79.

    Colley DG, Garcia AA, Lambertucci JR, Parra JC, Katz N, Rocha RS, Gazzinelli G, 1986. Immune responses during human schistosomiasis. XII. Differential responsiveness in patients with hepatosplenic disease. Am J Trop Med Hyg 35: 793802.

    • Search Google Scholar
    • Export Citation
  • 80.

    Grogan JL, Kremsner PG, Deelder AM, Yazdanbakhsh M, 1996. Elevated proliferation and interleukin-4 release from CD4+ cells after chemotherapy in human Schistosoma haematobium infection. Eur J Immunol 26: 13651370.

    • Search Google Scholar
    • Export Citation
  • 81.

    King CL et al., 1996. Cytokine control of parasite-specific anergy in human urinary schistosomiasis. IL-10 modulates lymphocyte reactivity. J Immunol 156: 47154721.

    • Search Google Scholar
    • Export Citation
  • 82.

    Falcao PL, Malaquias LC, Martins-Filho OA, Silveira AM, Passos VM, Prata A, Gazzinelli G, Coffman RL, Correa-Oliveira R, 1998. Human schistosomiasis mansoni: IL-10 modulates the in vitro granuloma formation. Parasite Immunol 20: 447454.

    • Search Google Scholar
    • Export Citation
  • 83.

    Malaquias LC, Falcao PL, Silveira AM, Gazzinelli G, Prata A, Coffman RL, Pizziolo V, Souza CP, Colley DG, Correa-Oliveira R, 1997. Cytokine regulation of human immune response to Schistosoma mansoni: analysis of the role of IL-4, IL-5 and IL-10 on peripheral blood mononuclear cell responses. Scand J Immunol 46: 393398.

    • Search Google Scholar
    • Export Citation
  • 84.

    Watanabe K, Mwinzi PN, Black CL, Muok EM, Karanja DM, Secor WE, Colley DG, 2007. T regulatory cell levels decrease in people infected with Schistosoma mansoni on effective treatment. Am J Trop Med Hyg 77: 676682.

    • Search Google Scholar
    • Export Citation
  • 85.

    Zaccone P, Burton O, Miller N, Jones FM, Dunne DW, Cooke A, 2009. Schistosoma mansoni egg antigens induce Treg that participate in diabetes prevention in NOD mice. Eur J Immunol 39: 10981107.

    • Search Google Scholar
    • Export Citation
  • 86.

    Turner JD, Jackson JA, Faulkner H, Behnke J, Else KJ, Kamgno J, Boussinesq M, Bradley JE, 2008. Intensity of intestinal infection with multiple worm species is related to regulatory cytokine output and immune hyporesponsiveness. J Infect Dis 197: 12041212.

    • Search Google Scholar
    • Export Citation
  • 87.

    Figueiredo CA, Barreto ML, Rodrigues LC, Cooper PJ, Silva NB, Amorim LD, Alcantara-Neves NM, 2010. Chronic intestinal helminth infections are associated with immune hyporesponsiveness and induction of a regulatory network. Infect Immun 78: 31603167.

    • Search Google Scholar
    • Export Citation
  • 88.

    Falcone FH, Rossi AG, Sharkey R, Brown AP, Pritchard DI, Maizels RM, 2001. Ascaris suum-derived products induce human neutrophil activation via a G protein-coupled receptor that interacts with the interleukin-8 receptor pathway. Infect Immun 69: 40074018.

    • Search Google Scholar
    • Export Citation
  • 89.

    Wammes LJ et al., 2016. Community deworming alleviates geohelminth-induced immune hyporesponsiveness. Proc Natl Acad Sci USA 113: 1252612531.

  • 90.

    Hartmann S, Lucius R, 2003. Modulation of host immune responses by nematode cystatins. Int J Parasitol 33: 12911302.

  • 91.

    Broadhurst MJ, Leung JM, Kashyap V, McCune JM, Mahadevan U, McKerrow JH, Loke P, 2010. IL-22+ CD4+ T cells are associated with therapeutic Trichuris trichiura infection in an ulcerative colitis patient. Sci Transl Med 2: 60ra88.

    • Search Google Scholar
    • Export Citation
  • 92.

    Correale J, Farez M, 2007. Association between parasite infection and immune responses in multiple sclerosis. Ann Neurol 61: 97108.

  • 93.

    Zaiss MM, Harris NL, 2016. Interactions between the intestinal microbiome and helminth parasites. Parasite Immunol 38: 511.

  • 94.

    Macpherson AJ, Harris NL, 2004. Interactions between commensal intestinal bacteria and the immune system. Nat Rev Immunol 4: 478485.

  • 95.

    McCoy KD, Burkhard R, Geuking MB, 2019. The microbiome and immune memory formation. Immunol Cell Biol 97: 625635.

  • 96.

    Vallianou NG, Tzortzatou-Stathopoulou F, 2019. Microbiota and cancer: an update. J Chemother 31: 5963.

  • 97.

    Kather JN, Halama N, 2019. Harnessing the innate immune system and local immunological microenvironment to treat colorectal cancer. Br J Cancer 120: 871882.

    • Search Google Scholar
    • Export Citation
  • 98.

    McKenney EA, Williamson L, Yoder AD, Rawls JF, Bilbo SD, Parker W, 2015. Alteration of the rat cecal microbiome during colonization with the helminth Hymenolepis diminuta. Gut Microbes 6: 182193.

    • Search Google Scholar
    • Export Citation
  • 99.

    Li RW, Li W, Sun J, Yu P, Baldwin RL, Urban JF, 2016. The effect of helminth infection on the microbial composition and structure of the caprine abomasal microbiome. Sci Rep 6: 20606.

    • Search Google Scholar
    • Export Citation
  • 100.

    Broadhurst MJ et al., 2012. Therapeutic helminth infection of macaques with idiopathic chronic diarrhea alters the inflammatory signature and mucosal microbiota of the colon. PLoS Pathog 8: e1003000.

    • Search Google Scholar
    • Export Citation
  • 101.

    Peachey LE, Jenkins TP, Cantacessi C, 2017. This gut ain’t big enough for both of us, or is it? Helminth-microbiota interactions in veterinary species. Trends Parasitol 33: 619632.

    • Search Google Scholar
    • Export Citation
  • 102.

    Li RW, Wu S, Li W, Navarro K, Couch RD, Hill D, Urban JF Jr., 2012. Alterations in the porcine colon microbiota induced by the gastrointestinal nematode Trichuris suis. Infect Immun 80: 21502157.

    • Search Google Scholar
    • Export Citation
  • 103.

    Martin I et al., 2019. The effect of gut microbiome composition on human immune responses: an exploration of interference by helminth infections. Front Genet 10: 1028.

    • Search Google Scholar
    • Export Citation
  • 104.

    Rosa BA et al., 2018. Differential human gut microbiome assemblages during soil-transmitted helminth infections in Indonesia and Liberia. Microbiome 6: 33.

    • Search Google Scholar
    • Export Citation
  • 105.

    Cantacessi C, Giacomin P, Croese J, Zakrzewski M, Sotillo J, McCann L, Nolan MJ, Mitreva M, Krause L, Loukas A, 2014. Impact of experimental hookworm infection on the human gut microbiota. J Infect Dis 210: 14311434.

    • Search Google Scholar
    • Export Citation
  • 106.

    Easton AV, Quinones M, Vujkovic-Cvijin I, Oliveira RG, Kepha S, Odiere MR, Anderson RM, Belkaid Y, Nutman TB, 2019. The impact of anthelmintic treatment on human gut microbiota based on cross-sectional and pre- and postdeworming comparisons in western Kenya. MBio 10: e00519.

    • Search Google Scholar
    • Export Citation
  • 107.

    Brosschot TP, Reynolds LA, 2018. The impact of a helminth-modified microbiome on host immunity. Mucosal Immunol 11: 10391046.

  • 108.

    Johnston CJC et al., 2017. A structurally distinct TGF-beta mimic from an intestinal helminth parasite potently induces regulatory T cells. Nat Commun 8: 1741.

    • Search Google Scholar
    • Export Citation
  • 109.

    O’Mahony C et al., 2008. Commensal-induced regulatory T cells mediate protection against pathogen-stimulated NF-kappaB activation. PLoS Pathog 4: e1000112.

    • Search Google Scholar
    • Export Citation
  • 110.

    Round JL, Mazmanian SK, 2010. Inducible Foxp3+ regulatory T-cell development by a commensal bacterium of the intestinal microbiota. Proc Natl Acad Sci USA 107: 1220412209.

    • Search Google Scholar
    • Export Citation
  • 111.

    Atarashi K et al., 2011. Induction of colonic regulatory T cells by indigenous Clostridium species. Science 331: 337341.

  • 112.

    Atarashi K et al., 2013. Treg induction by a rationally selected mixture of Clostridia strains from the human microbiota. Nature 500: 232236.

  • 113.

    Narushima S, Sugiura Y, Oshima K, Atarashi K, Hattori M, Suematsu M, Honda K, 2014. Characterization of the 17 strains of regulatory T cell-inducing human-derived Clostridia. Gut Microbes 5: 333339.

    • Search Google Scholar
    • Export Citation
  • 114.

    Smits HH et al., 2005. Selective probiotic bacteria induce IL-10-producing regulatory T cells in vitro by modulating dendritic cell function through dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin. J Allergy Clin Immunol 115: 12601267.

    • Search Google Scholar
    • Export Citation
  • 115.

    Jang SO, Kim HJ, Kim YJ, Kang MJ, Kwon JW, Seo JH, Kim HY, Kim BJ, Yu J, Hong SJ, 2012. Asthma prevention by lactobacillus rhamnosus in a mouse model is associated with CD4(+)CD25(+)Foxp3(+) T cells. Allergy Asthma Immunol Res 4: 150156.

    • Search Google Scholar
    • Export Citation
  • 116.

    Ohnmacht C et al., 2015. MUCOSAL IMMUNOLOGY. The microbiota regulates type 2 immunity through RORgammat(+) T cells. Science 349: 989993.

  • 117.

    Rausch S, Held J, Fischer A, Heimesaat MM, Kuhl AA, Bereswill S, Hartmann S, 2013. Small intestinal nematode infection of mice is associated with increased enterobacterial loads alongside the intestinal tract. PLoS One 8: e74026.

    • Search Google Scholar
    • Export Citation
  • 118.

    Kreisinger J, Bastien G, Hauffe HC, Marchesi J, Perkins SE, 2015. Interactions between multiple helminths and the gut microbiota in wild rodents. Philos Trans R Soc Lond B Biol Sci 370: 20140295.

    • Search Google Scholar
    • Export Citation
  • 119.

    Reynolds LA, Smith KA, Filbey KJ, Harcus Y, Hewitson JP, Redpath SA, Valdez Y, Yebra MJ, Finlay BB, Maizels RM, 2014. Commensal-pathogen interactions in the intestinal tract: Lactobacilli promote infection with, and are promoted by, helminth parasites. Gut Microbes 5: 522532.

    • Search Google Scholar
    • Export Citation
  • 120.

    Graham AL, 2008. Ecological rules governing helminth-microparasite coinfection. Proc Natl Acad Sci USA 105: 566570.

  • 121.

    Salgame P, Yap GS, Gause WC, 2013. Effect of helminth-induced immunity on infections with microbial pathogens. Nat Immunol 14: 11181126.

  • 122.

    Chen CC, Louie S, McCormick B, Walker WA, Shi HN, 2005. Concurrent infection with an intestinal helminth parasite impairs host resistance to enteric Citrobacter rodentium and enhances Citrobacter-induced colitis in mice. Infect Immun 73: 54685481.

    • Search Google Scholar
    • Export Citation
  • 123.

    Reese TA et al., 2014. Helminth infection reactivates latent gamma-herpesvirus via cytokine competition at a viral promoter. Science 345: 573577.

    • Search Google Scholar
    • Export Citation
  • 124.

    Osborne LC et al., 2014. Coinfection. Virus-helminth coinfection reveals a microbiota-independent mechanism of immunomodulation. Science 345: 578582.

    • Search Google Scholar
    • Export Citation
  • 125.

    Gazzinelli-Guimaraes PH et al., 2017. Concomitant helminth infection downmodulates the vaccinia virus-specific immune response and potentiates virus-associated pathology. Int J Parasitol 47: 110.

    • Search Google Scholar
    • Export Citation
  • 126.

    Veldhoen M, Heeney JL, 2014. A helminth-mediated viral awakening. Trends Immunol 35: 452453.

  • 127.

    Damania B, Dittmer DP, 2014. What lies within: coinfections and immunity. Cell Host Microbe 16: 145147.

  • 128.

    Shapira-Nahor O, Kalinkovich A, Weisman Z, Greenberg Z, Nahmias J, Shapiro M, Panet A, Bentwich Z, 1998. Increased susceptibility to HIV-1 infection of peripheral blood mononuclear cells from chronically immune-activated individuals. AIDS 12: 17311733.

    • Search Google Scholar
    • Export Citation
  • 129.

    Chachage M et al., 2014. Helminth-associated systemic immune activation and HIV co-receptor expression: response to albendazole/praziquantel treatment. PLoS Negl Trop Dis 8: e2755.

    • Search Google Scholar
    • Export Citation
  • 130.

    Secor WE, Shah A, Mwinzi PM, Ndenga BA, Watta CO, Karanja DM, 2003. Increased density of human immunodeficiency virus type 1 coreceptors CCR5 and CXCR4 on the surfaces of CD4(+) T cells and monocytes of patients with Schistosoma mansoni infection. Infect Immun 71: 66686671.

    • Search Google Scholar
    • Export Citation
  • 131.

    Borkow G, Bentwich Z, 2006. HIV and helminth co-infection: is deworming necessary? Parasite Immunol 28: 605612.

  • 132.

    Bentwich Z, Weisman Z, Moroz C, Bar-Yehuda S, Kalinkovich A, 1996. Immune dysregulation in Ethiopian immigrants in Israel: relevance to helminth infections? Clin Exp Immunol 103: 239243.

    • Search Google Scholar
    • Export Citation
  • 133.

    Blish CA, Sangare L, Herrin BR, Richardson BA, John-Stewart G, Walson JL, 2010. Changes in plasma cytokines after treatment of Ascaris lumbricoides infection in individuals with HIV-1 infection. J Infect Dis 201: 18161821.

    • Search Google Scholar
    • Export Citation
  • 134.

    Borkow G, Teicher C, Bentwich Z, 2007. Helminth-HIV coinfection: should we deworm? PLoS Negl Trop Dis 1: e160.

  • 135.

    Means AR, Burns P, Sinclair D, Walson JL, 2016. Antihelminthics in helminth-endemic areas: effects on HIV disease progression. Cochrane Database Syst Rev 4: CD006419.

    • Search Google Scholar
    • Export Citation
  • 136.

    Nalwoga A et al., 2019. Kaposi’s sarcoma-associated herpesvirus seropositivity is associated with parasite infections in Ugandan fishing communities on Lake Victoria islands. PLoS Negl Trop Dis 13: e0007776.

    • Search Google Scholar
    • Export Citation
  • 137.

    Passmore JS, Williamson A, 2016. Host immune responses associated with clearance or persistence of human papillomavirus infections. Curr Obstet Gynecol Rep 5: 177188.

    • Search Google Scholar
    • Export Citation
  • 138.

    Tristram A, Fiander A, 2001. Natural history of cervical human papillomavirus. Lancet 358: 1550.

  • 139.

    Egawa N, Egawa K, Griffin H, Doorbar J, 2015. Human papillomaviruses; epithelial tropisms, and the development of neoplasia. Viruses 7: 38633890.

    • Search Google Scholar
    • Export Citation
  • 140.

    van Riet E, Hartgers FC, Yazdanbakhsh M, 2007. Chronic helminth infections induce immunomodulation: consequences and mechanisms. Immunobiology 212: 475490.

    • Search Google Scholar
    • Export Citation
  • 141.

    Lo NC, Lai YS, Karagiannis-Voules DA, Bogoch II, Coulibaly JT, Bendavid E, Utzinger J, Vounatsou P, Andrews JR, 2016. Assessment of global guidelines for preventive chemotherapy against schistosomiasis and soil-transmitted helminthiasis: a cost-effectiveness modelling study. Lancet Infect Dis 16: 10651075.

    • Search Google Scholar
    • Export Citation
  • 142.

    WHO, 2018. Reaching Girls and Women of Reproductive Age with Deworming: Report of the Advisory Group on Deworming in Girls and Women of Reproductive Age. Rockefeller Foundation Bellagio Center, Bellagio, Italy 28–30 June 2017. Montresor A Geneva, Switzerland: World Health Organization.

    • Search Google Scholar
    • Export Citation
  • 143.

    Rowan-Nash AD, Korry BJ, Mylonakis E, Belenky P, 2019. Cross-domain and viral interactions in the microbiome. Microbiol Mol Biol Rev 83: e0004418.

    • Search Google Scholar
    • Export Citation
 
 
 
 

 

 
 

 

 

 

 

 

 

Gut Helminth Infection-Induced Immunotolerance and Consequences for Human Papillomavirus Persistence

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  • 1 Department of Medicine, Section of Infectious Diseases, Baylor College of Medicine, Houston, Texas;
  • | 2 Department of Medicine, Section of Health Services Research, Center for Innovations in Quality, Effectiveness, and Safety (IQuESt), Michael E. DeBakey VA Medical Center, Houston, Texas;
  • | 3 National School of Tropical Medicine, Baylor College of Medicine, Houston, Texas;
  • | 4 Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland;
  • | 5 Department of Epidemiology, University of Texas MD Anderson Cancer Center, Houston, Texas;
  • | 6 Department of General Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas;
  • | 7 Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, Maryland

ABSTRACT.

Cervical cancer, a malignancy caused by persistent human papillomavirus (HPV) infection, develops in more than 500,000 women annually. More than 90% of deaths from cervical cancer occur in low- and middle-income countries. A common epidemiological feature of countries with high cervical cancer incidence is a high burden of intestinal helminth infection. The ability of intestinal helminths to trigger immunoregulation, resulting in a “tolerogenic” systemic immune environment, provides fertile soil for the persistence of oncogenic viruses such as HPV. Animal models have shown that intestinal helminth infection permits the persistence of some viruses, however, HPV-specific and human studies are lacking. Large, well-organized trials evaluating the consequences of intestinal helminth infection on the human immune system and HPV persistence may lead to improved strategies for HPV prevention in helminth-endemic regions of the world. Additionally, such studies would offer insight into the specific ways that intestinal helminth infection contributes to immunomodulation, which could identify new therapeutic targets for a range of diseases, from inflammatory disorders to cancer. In this review, we discuss the evidence for helminth-induced systemic and local immune dysregulation, discuss possible mechanisms by which chronic intestinal helminth infection may facilitate HPV persistence, and suggest novel helminth-related interventions that could offer a high leverage (if somewhat unconventional) approach to HPV and cervical cancer control in resource-constrained regions.

Author Notes

Address correspondence to Eva H. Clark, Houston HSR&D Center for Innovations in Quality, Effectiveness and Safety (IQuESt), Baylor College of Medicine, Michael E. DeBakey VA Medical Center, 2450 Holcombe Blvd., Suite 01Y, Houston, TX 77021. E-mail: eva.clark@bcm.edu

Financial support: This work was supported by VA Health Services Research & Development Center of Innovation grant CIN 13-413 (E. H. C. receives salary support in part from the Houston VA HSR&D Center for Innovations in Quality, Effectiveness and Safety [CIN13-413] Advanced Fellowships Program in Health Services Research).

Authors’ addresses: Eva H. Clark, Department of Medicine, Section of Infectious Diseases, Baylor College of Medicine, Houston, TX, Department of Medicine, Section of Health Services Research, Center for Innovations in Quality, Effectiveness, and Safety (IQuESt), Michael E. DeBakey VA Medical Center, Houston, TX, and National School of Tropical Medicine, Baylor College of Medicine, Houston, TX, E-mail: eva.clark@bcm.edu. Robert H. Gilman, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, E-mail: gilmanbob@gmail.com. Elizabeth Y. Chiao, Department of Epidemiology, University of Texas MD Anderson Cancer Center, Houston, TX, and Department of General Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, E-mail: eychiao@mdanderson.org. Patti E. Gravitt, Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, MD, E-mail: pgravitt@som.umaryland.edu.

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