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Open Access 01-02-2008 | Original Article

Perceived Stress is Associated with Impaired T-Cell Response to HPV16 in Women with Cervical Dysplasia

Authors: Carolyn Y. Fang, Ph.D., Suzanne M. Miller, Ph.D., Dana H. Bovbjerg, Ph.D., Cynthia Bergman, M.D., Mitchell I. Edelson, M.D., Norman G. Rosenblum, M.D., Ph.D., Betsy A. Bove, Ph.D., Andrew K. Godwin, Ph.D., Donald E. Campbell, Ph.D., Steven D. Douglas, M.D.

Published in: Annals of Behavioral Medicine | Issue 1/2008

Abstract

Background

Infection with high-risk subtypes of human papillomavirus (HPV) is a central factor in the development of cervical neoplasia. Cell-mediated immunity against HPV16 plays an important role in the resolution of HPV infection and in controlling cervical disease progression. Research suggests that stress is associated with cervical disease progression, but few studies have examined the biological mechanisms that may be driving this association.

Purpose

This study examines whether stress is associated with immune response to HPV16 among women with cervical dysplasia.

Methods

Seventy-four women presenting for colposcopy completed measures of health behaviors, stressful life events and perceived stress. A blood sample was obtained to evaluate proliferative T-cell response to HPV16, and a cervical sample was obtained during gynecologic exam for HPV-typing.

Results

More than 55% tested positive for one or more HPV subtypes. Women who did not show proliferative responses to HPV (i.e. non-responders) were more likely to be HPV⁺ compared to women who had a response (i.e. responders). Consistent with study hypotheses, logistic regression revealed that higher levels of perceived stress were associated with a non-response to HPV16, controlling for relevant covariates. Stressful life events were not associated with T-cell response to HPV.

Conclusions

Higher levels of perceived stress are associated with impaired HPV-specific immune response in women with cervical dysplasia, suggesting a potential mechanism by which stress may influence cervical disease progression.

Koutsky LA, Holmes KK, Critchlow CW, et al. A cohort study of the risk of cervical intraepithelial neoplasia grade 2 or 3 in relation to papillomavirus infection. N Engl J Med. 1992; 327: 1272–1278.PubMedCrossRef

Stoler MH. A brief synopsis of the role of human papillomaviruses in cervical carcinogenesis. Am J Obstet Gynecol. 1996; 175: 1091–1098.PubMedCrossRef

Wolf JK, Franco EL, Arbeit JM, et al. Innovations in understanding the biology of cervical cancer. Cancer. 2003; 98: 2064–2069.PubMedCrossRef

Franco EL, Schlecht NF, Saslow D. The epidemiology of cervical cancer. Cancer J. 2003; 9: 348–359.PubMedCrossRef

Mitchell MF, Tortolero-Luna G, Wright T, et al. Cervical human papillomavirus infection and intraepithelial neoplasia: a review. J Natl Cancer Inst Monographs. 1996; 21: 17–25.PubMed

Schoell WMJ, Janicek MF, Mirhashemi R. Epidemiology and biology of cervical cancer. Sem Surg Oncol. 1999; 16: 203–211.CrossRef

Dunne EF, Unger ER, Sternberg M, et al. Prevalence of HPV infection among females in the United States. J Am Med Assoc. 2007; 297: 813–819.CrossRef

Castle PE, Wacholder S, Lorincz AT, et al. A prospective study of high-grade cervical neoplasia risk among human papillomavirus-infected women. J Natl Cancer Inst. 2002; 94: 1406–1414.PubMed

Schiffman MH, Castle P. Epidemiologic studies of a necessary causal risk factor: Human papillomavirus infection and cervical neoplasia. J Natl Cancer Inst. 2003; 95: E2.PubMed

10.

Castle PE, Solomon D, Schiffman M, Wheeler CM. Human papillomavirus type 16 infections and 2-year absolute risk of cervical precancer in women with equivocal or mild cytologic abnormalities. J Natl Cancer Inst. 2005; 97: 1066–1071.PubMed

11.

Vermund SH, Kelley KF, Klein RS, et al. High risk of human papillomavirus infection and cervical squamous intraepithelial lesions among women with symptomatic human immunodeficiency virus infection. Am J Obstet Gynecol. 1991; 165: 392–400.PubMed

12.

Maiman M. Management of cervical neoplasia in human immunodeficiency virus-infected women. J Natl Cancer Inst Monographs. 1998; 1998: 43–49.

13.

Hawes SE, Critchlow CW, Sow PS, et al. Incident high-grade squamous intraepithelial lesions in Senegalese women with and without human immunodeficiency virus type 1 (HIV-1) and HIV-2. J Natl Cancer Inst. 2006; 98: 100–109.PubMedCrossRef

14.

Kadish AS, Ho GYF, Burk RD, et al. Lymphoproliferative responses to human papillomavirus (HPV) type 16 proteins E6 and E7: Outcome of HPV infection and associated neoplasia. J Natl Cancer Inst. 1997; 89: 1285–1293.PubMedCrossRef

15.

Kadish AS, Timmins P, Wang Y, et al. Regression of cervical intraepithelial neoplasia and loss of human papillomavirus (HPV) infection is associated with cell-mediated immune responses to an HPV type 16 E7 peptide. Cancer Epidemiol Biomark Prev. 2002; 11: 483–488.

16.

Koutsky LA, Ault KA, Wheeler CM, et al. A controlled trial of a human papillomavirus type 16 vaccine. N Engl J Med. 2002; 347: 1645–1651.PubMedCrossRef

17.

Washam C. Two HPV vaccines yielding similar success. J Natl Cancer Inst. 2005; 97: 1030.

18.

Villa LL, Costa RL, Petta CA, et al. Prophylactic quadrivalent human papillomavirus (types 6, 11, 16, and 18) L1 virus-like particle vaccine in young women: a randomised double-blind placebo-controlled multicentre phase II efficacy trial. Lancet Oncol. 2005; 6: 271–278.PubMedCrossRef

19.

Mahdavi A, Monk BJ. Vaccines against human papillomavirus and cervical cancer: promises and challenges. Oncologist. 2005; 10: 528–538.PubMedCrossRef

20.

Shaw AR. Human papillomavirus vaccines in development: if they’re successful in clinical trials, how will they be implemented? Gynecol Oncol. 2005; 99: S246–S248.PubMedCrossRef

21.

Washam C. Targeting teens and adolescents for HPV vaccine could draw fire. J Natl Cancer Inst. 2005; 97: 1030–1031.

22.

Coker AL, Bond S, Madeleine MM, Luchok K, Pirisi L. Psychosocial stress and cervical neoplasia risk. Psychosom Med. 2003; 65: 644–651.PubMedCrossRef

23.

Pereira DB, Antoni MH, Danielson A, et al. Life stress and cervical squamous intraepithelial lesions in women with human papillomavirus and human immunodeficiency virus. Psychosom Med. 2003; 65: 427–434.PubMedCrossRef

24.

Glaser R, Kiecolt-Glaser JK. Chronic stress modulates the virus-specific immune response to latent herpes simplex virus type 1. Annals Behav Med. 1997; 19: 78–82.

25.

Kang DH, Fox C. Neuroendocrine and leukocyte responses and pulmonary function to acute stressors. Annals of Behav Med. 2000; 22: 276–285.

26.

Kiecolt-Glaser JK, McGuire L, Robles TF, Glaser R. Psychoneuroimmunology: Psychological influences on immune function and health. J Consult Clin Psychol. 2002; 70: 537–547.PubMedCrossRef

27.

Kiecolt-Glaser JK, Robles TF, Heffner KL, Loving TJ, Glaser R. Psycho-oncology and cancer: psychoneuroimmunology and cancer. Ann Oncol. 2002; 13(Suppl 4): 165–169.PubMed

28.

DeLongis A, Coyne J, Dakof G, Folkman S, Lazarus RS. Relationship of daily hassles, uplifts, and major life events to health status. Health Psychol. 1982; 1: 119–136.CrossRef

29.

Holmes TH, Rahe RH. The social readjustment rating scale. J Psychosom Res. 1967; 11: 213–218.PubMedCrossRef

30.

Cohen S, Kamarck TW, Mermelstein R. A global measure of perceived stress. J Health Soc Behav. 1983; 24: 385–396.PubMedCrossRef

31.

Cohen S, Doyle WJ, Skoner DP. Psychological stress, cytokine production, and severity of upper respiratory illness. Psychosom Med. 1999; 61: 175–180.PubMed

32.

Cohen S, Hamrick N, Rodriguez MS, et al. Reactivity and vulnerability to stress-associated risk for upper respiratory illness. Psychosom Med. 2002; 64: 302–310.PubMedCrossRef

33.

Cohen S, Miller G, Rabin B. Psychological stress and antibody response to immunization: A critical review of the human literature. Psychosom Med. 2001; 63: 7–18.PubMed

34.

Cohen S, Rabin BS. Psychologic stress, immunity, and cancer. J Natl Cancer Inst. 1998; 90: 3–4.PubMedCrossRef

35.

Cohen S, Tyrrell DA, Smith AP. Psychological stress and susceptibility to the common cold. N Engl J Med. 1991; 325: 606–612.PubMedCrossRef

36.

Luxton JC, Rowe AJ, Cridland JC, et al. Proliferative T cell responses to the human papillomavirus type 16 E7 protein in women with cervical dysplasia and cervical carcinoma and in healthy individuals. J Gen Virol. 1996; 77: 1585–1593.PubMed

37.

Nakagawa M, Stites DP, Farhat S, et al. T-cell proliferative response to human papillomavirus type 16 peptides: Relationship to cervical intraepithelial neoplasia. Clin Diagn Lab Immunol. 1996; 3: 205–210.PubMed

38.

Douglas SD, Hoffman PF, Borjeson J, Chessin LN. Studies on human peripheral blood lymphocytes in vitro. 3. Fine structural features of lymphocyte transformation by pokeweed mitogen. J Immunol. 1967; 98: 17–30.PubMed

39.

Douglas SD, Kamin RM, Fudenberg HH. Human lymphocyte response to phytomitogens in vitro: normal, agammaglobulinemic and paraproteinemic individuals. J Immunol. 1969; 103: 1185–1195.PubMed

40.

Borkowsky W, Stanley K, Douglas SD, et al. Immunologic response to combination nucleoside analogue plus protease inhibitor therapy in stable antiretroviral therapy-experienced human immunodeficiency virus-infected children. J Infect Dis. 2000; 182: 96–103.PubMedCrossRef

41.

Sarkar AK, Tortolero-Luna G, Follen M, Sastry KJ. Inverse correlation of cellular immune responses specific to synthetic peptides from the E6 and E7 oncoproteins of HPV-16 with recurrence of cervical intraepithelial neoplasia in a cross-sectional study. Gynecol Oncol. 2005; 99: S251–S261.PubMedCrossRef

42.

Fang CY, Miller SM, Mills M, et al. The effects of avoidance on cytotoxic/suppressor T cells in women with cervical lesions. Psychooncology. 2003; 12: 590–598.PubMedCrossRef

43.

Gill D, Bible J, Biswas C, et al. Proliferative T-cell responses to human papillomavirus type 16 E5 are decreased amongst women with high-grade neoplasia. J Gen Virol. 1998; 79: 1971–1976.PubMed

44.

Steele JC, Mann CH, Rookes S, et al. T-cell responses to human papillomavirus type 16 among women with different grades of cervical neoplasia. Br J Cancer. 2005; 93: 248–259.PubMedCrossRef

45.

Brummer O, Hollwitz B, Bohmer G, Kuhnle H, Petry KU. Human papillomavirus-type persistence patterns predict the clinical outcome of cervical intraepithelial neoplasia. Gynecol Oncol. 2006; 102: 517–522.PubMedCrossRef

46.

Goodkin K, Antoni MH, Blaney PH. Stress and hopelessness in the promotion of cervical intraepithelial neoplasia to invasive squamous cell carcinoma of the cervix. J Psychosom Res. 1986; 30: 67–76.PubMedCrossRef

47.

Kiecolt-Glaser JK, McGuire L, Robles TF, Glaser R. Psychoneuroimmunology and psychosomatic medicine: Back to the future. Psychosom Med. 2002; 64: 15–28.PubMed

48.

Paik IH, Toh KY, Lee C, Kim JJ, Lee SJ. Psychological stress may induce increased humoral and decreased cellular immunity. Behav Med. 2000; 26: 139–141.PubMedCrossRef

49.

Clerici M, Merola M, Ferrario E, et al. Cytokine production patterns in cervical intraepithelial neoplasia: association with human papillomavirus infection. J Natl Cancer Inst. 1997; 89: 245–250.PubMedCrossRef

50.

Peralta-Ramirez MI, Jimenez-Alonso J, Godoy-Garcia JF, Perez-Garcia M. The effects of daily stress and stressful life events on the clinical symptomatology of patients with lupus erythematosus. Psychosom Med. 2004; 66: 788–794.PubMedCrossRef

51.

Hamrick N, Cohen S, Rodriguez MS. Being popular can be healthy or unhealthy: stress, social network diversity, and incidence of upper respiratory infection. Health Psychol. 2002; 21: 294–298.PubMedCrossRef

52.

Folkman S. Personal control and stress and coping processes: A theoretical analysis. J Pers Soc Psychol. 1984; 46: 839–852.PubMedCrossRef

53.

Folkman S, Lazarus RS, Dunkel-Schetter C, De Longis A, Gruen RJ. Dynamics of a stressful encounter: Cognitive appraisal, coping, and encounter outcomes. J Pers Soc Psychol. 1986; 50: 992–1003.PubMedCrossRef

54.

Maier KJ, Waldstein SR, Synowski SJ. Relation of cognitive appraisal to cardiovascular reactivity, affect, and task engagement. Annals Behav Med. 2003; 26: 32–41.CrossRef

55.

Bontkes HJ, de Gruijl TD, Walboomers JM, et al. Immune responses against human papillomavirus (HPV) type 16 virus-like particles in a cohort study of women with cervical intraepithelial neoplasia. II. Systemic but not local IgA responses correlate with clearance of HPV-16. J Gen Virol. 1999; 80(Pt 2): 409–417.PubMed

Title: Perceived Stress is Associated with Impaired T-Cell Response to HPV16 in Women with Cervical Dysplasia
Authors: Carolyn Y. Fang, Ph.D.
Suzanne M. Miller, Ph.D.
Dana H. Bovbjerg, Ph.D.
Cynthia Bergman, M.D.
Mitchell I. Edelson, M.D.
Norman G. Rosenblum, M.D., Ph.D.
Betsy A. Bove, Ph.D.
Andrew K. Godwin, Ph.D.
Donald E. Campbell, Ph.D.
Steven D. Douglas, M.D.
Publication date: 01-02-2008
Publisher: Springer-Verlag
Published in: Annals of Behavioral Medicine / Issue 1/2008
Print ISSN: 0883-6612
Electronic ISSN: 1532-4796
DOI: https://doi.org/10.1007/s12160-007-9007-6

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Perceived Stress is Associated with Impaired T-Cell Response to HPV16 in Women with Cervical Dysplasia

Abstract

Background

Purpose

Methods

Results

Conclusions

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Background

Purpose

Methods

Results

Conclusions

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