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HPV Infection and Gynecological Cancers

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Preventive Oncology for the Gynecologist

Abstract

Human papilloma viruses (HPVs) are sexually transmitted, double-stranded oncogenic DNA viruses. HPV infections account for approximately 5% of all malignancies worldwide. Almost all cervical carcinomas (squamous cell carcinoma and adenocarcinoma) and a significant proportion of other anogenital carcinomas (vulvovaginal, anal, penile carcinomas) and oropharyngeal carcinomas are attributed to HPV infections. The common high-risk types seen in preinvasive and invasive lesions of the cervix are HPV 16 and HPV 18. The other common HPV types are HPV 6 and HPV 11, which belong to the low-risk category and are associated with genital warts. Most HPV infections are cleared within 6–12 months by the cell-mediated host immune response. A small proportion of infections that persist can develop into preinvasive lesions, which have a risk of progression to malignancy. The cofactors for persistence and progression of infection are smoking, parity, hormonal influences, other infections like HIV, etc. E6 and E7 proteins inhibit p53 and RB tumor suppressor genes, respectively, and are responsible for viral oncogenicity in the high-risk HPV types. Primary prevention by vaccination and screening by cytology and HPV DNA testing are available.

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References

  1. Nobel Media. Harald zur Hausen – Biographica [internet]. Available from: <http://www.nobelprize.org/nobel_prizes/medicine/laureates/2008/hausen-bio.html>.

  2. de Martel C, Ferlay J, Franceschi S, Vignat J, Bray F, Forman D, et al. Global burden of cancers attributable to infections in 2008: a review and synthetic analysis. Lancet Oncol. 2012;13:607–15.

    Article  PubMed  Google Scholar 

  3. Bosch FX, Broker TR, Forman D, Moscicki AB, Gillison ML, Doorbar J, et al. Comprehensive control of human papillomavirus infections and related diseases. Vaccine. 2013;31(Suppl 8):11–31.

    Google Scholar 

  4. Bernard HU, Burk RD, Chen Z, van Doorslaer K, zur Hausen H, de Villiers EM. Classification of papillomaviruses (PVs) based on 189 PV types and proposal of taxonomic amendments. Virology. 2010;401:70–9.

    Article  CAS  PubMed  Google Scholar 

  5. de Villiers EM. Cross-roads in the classification of papillomaviruses. Virology. 2013;445:2–10.

    Article  PubMed  CAS  Google Scholar 

  6. IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. Human papillomaviruses. IARC Monogr Eval Carcinog Risks Hum. 2007;90:1–636.

    PubMed Central  Google Scholar 

  7. Doorbar J, Egawa N, Griffin H, Kranjec C, Murakami I. Human papillomavirus molecular biology and disease association. Rev Med Virol. 2015;25(Suppl 1):2–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Mindel A, Tideman R. HPV transmission — still feeling the way. Lancet. 1999;354:2097–8.

    Article  CAS  PubMed  Google Scholar 

  9. Frega A, Cenci M, Stentella P, Cipriano L, De Ioris A, Alderisio M, et al. Human papillomavirus in virgins and behaviour at risk. Cancer Lett. 2003;194:21–4.

    Article  CAS  PubMed  Google Scholar 

  10. Winer RL, Lee SK, Hughes JP, Adam DE, Kiviat NB, Koutsky LA. Genital human papillomavirus infection: incidence and risk factors in a cohort of female university students. Am J Epidemiol. 2003;157:218–26.

    Article  PubMed  Google Scholar 

  11. Sonnex C, Strauss S, Gray JJ. Detection of human papillomavirus DNA on the fingers of patients with genital warts. Sex Transm Infect. 1999;75:317–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Franco EL, Villa LL, Ruiz A, Costa MC. Transmission of cervical human papillomavirus infection by sexual activity: differences between low and high oncogenic risk types. J Infect Dis. 1995;172:756–63.

    Article  CAS  PubMed  Google Scholar 

  13. Kjaer SK, van den Brule AJC, Bock JE, Poll PA, Engholm G, Sherman ME, et al. Determinants for genital human papillomavirus (HPV) infection in 1000 randomly chosen young Danish women with normal Pap smear: are there different risk profiles for oncogenic and nononcogenic HPV types? Cancer Epidemiol Biomark Prev. 1997;6:799–805.

    CAS  Google Scholar 

  14. Rousseau MC, Franco EL, Villa LL, Sobrinho JP, Termini L, Prado JM, et al. A cumulative case–control study of risk factor profiles for oncogenic and nononcogenic cervical human papillomavirus infections. Cancer Epidemiol Biomark Prev. 2000;9:469–76.

    CAS  Google Scholar 

  15. Tenti P, Zappatore R, Migliora P, Spinillo A, Belloni C, Carnevali L. Perinatal transmission of human papillomavirus from gravidas with latent infections. Obstet Gynecol. 1999;93:475–9.

    CAS  PubMed  Google Scholar 

  16. Syrjänen S, Puranen M. Human papillomavirus infections in children: the potential role of maternal transmission. Crit Rev Oral Biol Med. 2000;11:259–74.

    Article  PubMed  Google Scholar 

  17. Sedlacek TV, Lindheim S, Eder C, Hasty L, Woodland M, Ludomirsky A, et al. Mechanism for human papillomavirus transmission at birth. Am J Obstet Gynecol. 1989;161:55–9.

    Article  CAS  PubMed  Google Scholar 

  18. Armbruster-Moraes E, Ioshimoto LM, Leao E, Zugaib M. Detection of human papillomavirus deoxyribonucleic acid sequences in amniotic fluid during different periods of pregnancy. Am J Obstet Gynecol. 1993;169:1074.

    Article  CAS  PubMed  Google Scholar 

  19. Grayson W, Rhemtula HA, Taylor LF, Allard U, Tiltman AJ. Detection of human papillomavirus in large cell neuroendocrine carcinoma of the uterine cervix: a study of 12 cases. J Clin Pathol. 2002;55:108–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Egawa K. Do human papillomaviruses target epidermal stem cells? Dermatology. 2003;207:251–4.

    Article  PubMed  Google Scholar 

  21. Schmitt A, Rochat A, Zeltner R, Borenstein L, Barrandon Y, Wettstein FO, et al. The primary target cells of the high-risk cottontail rabbit papillomavirus colocalize with hair follicle stem cells. J Virol. 1996;70:1912–22.

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Aksoy P, Gottschalk EY, Meneses PI. HPV entry into cells. Mutat Res Rev Mutat Res. 2017;772:13–22.

    Article  CAS  PubMed  Google Scholar 

  23. Pyeon D, Pearce SM, Lank SM, Ahlquist P, Lambert PF. Establishment of human papillomavirus infection requires cell cycle progression. PLoS Pathog. 2009;5:e1000318.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  24. Parish JL, Bean AM, Park RB, Androphy EJ. ChlR1 is required for loading papillomavirus E2 onto mitotic chromosomes and viral genome maintenance. Mol Cell. 2006;24:867–76.

    Article  CAS  PubMed  Google Scholar 

  25. McBride AA. Replication and partitioning of papillomavirus genomes. Adv Virus Res. 2008;72:155–205.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Hubert WG, Laimins LA. Human papillomavirus type 31 replication modes during the early phases of the viral life cycle depend on transcriptional and posttranscriptional regulation of E1 and E2 expression. J Virol. 2002;76:2263–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Stubenrauch F, Colbert AM, Laimins LA. Transactivation by the E2 protein of oncogenic human papillomavirus type 31 is not essential for early and late viral functions. J Virol. 1998;72:8115–23.

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Egawa N, Nakahara T, Ohno S, Narisawa-Saito M, Yugawa T, Fujita M, et al. The E1 protein of human papillomavirus type 16 is dispensable for maintenance replication of the viral genome. J Virol. 2012;86:3276–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Cheng S, Schmidt-Grimminger DC, Murant T, Broker TR, Chow LT. Differentiation-dependent up-regulation of the human papillomavirus E7 gene reactivates cellular DNA replication in suprabasal differentiated keratinocytes. Genes Dev. 1995;9:2335–49.

    Article  CAS  PubMed  Google Scholar 

  30. Peh WL, Middleton K, Christensen N, Nicholls P, Egawa K, Sotlar K, et al. Life cycle heterogeneity in animal models of human papillomavirus-associated disease. J Virol. 2002;76:10401–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Stanley M. Pathology and epidemiology of HPV infection in females. Gynecol Oncol. 2010;117:S5–S10.

    Article  PubMed  Google Scholar 

  32. Gariglio P, Gutiérrez J, Cortés E, Vázquez J. The role of retinoid deficiency and estrogens as cofactors in cervical cancer. Arch Med Res. 2009;40:449–65.

    Article  CAS  PubMed  Google Scholar 

  33. Ding DC, Chiang MH, Lai HC, Hsiung CA, Hsieh CY, Chu TY. Methylation of the long control region of HPV16 is related to the severity of cervical neoplasia. Eur J Obstet Gynecol Reprod Biol. 2009;147:215–20.

    Article  CAS  PubMed  Google Scholar 

  34. Jeon S, Allen-Hoffmann BL, Lambert PF. Integration of human papillomavirus type 16 into the human genome correlates with a selective growth advantage of cells. J Virol. 1995;69:2989–97.

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Jeon S, Lambert PF. Integration of human papillomavirus type 16 DNA into the human genome leads to increased stability of E6 and E7 mRNAs: implications for cervical carcinogenesis. Proc Natl Acad Sci U S A. 1995;92:1654–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Pett MR, Alazawi WO, Roberts I, Dowen S, Smith DI, Stanley MA, et al. Acquisition of high-level chromosomal instability is associated with integration of human papillomavirus type 16 in cervical keratinocytes. Cancer Res. 2004;64:1359–68.

    Article  CAS  PubMed  Google Scholar 

  37. Badaracco G, Venuti A, Sedati A, Marcante ML. HPV16 and HPV18 in genital tumors: significantly different levels of viral integration and correlation to tumor invasiveness. J Med Virol. 2002;67:574–82.

    Article  CAS  PubMed  Google Scholar 

  38. Fu L, Van Doorslaer K, Chen Z, Ristriani T, Masson M, Travé G, et al. Degradation of p53 by human Alphapapillomavirus E6 proteins shows a stronger correlation with phylogeny than oncogenicity. PLoS One. 2010;5(9):e12816.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  39. Zanier K, ould M’hamed ould Sidi A, Boulade-Ladame C, Rybin V, Chappelle A, Atkinson A, et al. Solution structure analysis of the HPV16 E6 oncoprotein reveals a self-association mechanism required for E6-mediated degradation of p53. Structure. 2012;20:604–17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Pim D, Banks L. Interaction of viral oncoproteins with cellular target molecules: infection with high-risk vs low-risk human papillomaviruses. APMIS. 2010;118:471–93.

    Article  CAS  PubMed  Google Scholar 

  41. Galloway DA, Gewin LC, Myers H, Luo W, Grandori C, Katzenellenbogen RA, et al. Regulation of telomerase by human papillomaviruses. Cold Spring Harb Symp Quant Biol. 2005;70:209–15.

    Article  CAS  PubMed  Google Scholar 

  42. Gewin L, Galloway DA. E box-dependent activation of telomerase by human papillomavirus type 16 E6 does not require induction of c-myc. J Virol. 2001;75:7198–201.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Klingelhutz AJ, Foster SA, McDougall JK. Telomerase activation by the E6 gene product of human papillomavirus type 16. Nature. 1996;380:79–82.

    Article  CAS  PubMed  Google Scholar 

  44. Barrow-Laing L, Chen W, Roman A. Low- and high-risk human papillomavirus E7 proteins regulate p130 differently. Virology. 2010;400:233–9.

    Article  CAS  PubMed  Google Scholar 

  45. Roman A. The human papillomavirus E7 protein shines a spotlight on the pRB family member, p130. Cell Cycle. 2006;5:567–8.

    Article  CAS  PubMed  Google Scholar 

  46. Klingelhutz AJ, Roman A. Cellular transformation by human papillomaviruses: lessons learned by comparing high- and low-risk viruses. Virology. 2012;424:77–98.

    Article  CAS  PubMed  Google Scholar 

  47. Felsani A, Mileo AM, Paggi MG. Retinoblastoma family proteins as key targets of the small DNA virus oncoproteins. Oncogene. 2006;25:5277–85.

    Article  CAS  PubMed  Google Scholar 

  48. Rodríguez AC, Schiffman M, Herrero R, Hildesheim A, Bratti C, Sherman ME, et al. Longitudinal study of human papillomavirus persistence and cervical intraepithelial neoplasia grade 2/3: critical role of duration of infection. J Natl Cancer Inst. 2010;102:315–24.

    Article  PubMed  PubMed Central  Google Scholar 

  49. Winer RL, Hughes JP, Feng Q, Xi LF, Cherne S, O’Reilly S, et al. Early natural history of incident, type-specific human papillomavirus infections in newly sexually active young women. Cancer Epidemiol Biomark Prev. 2011;20:699–707.

    Article  Google Scholar 

  50. Alizon S, Murall CL, Bravo IG. Why human papillomavirus acute infections matter. Viruses. 2017;9(10):e293.

    Article  PubMed  Google Scholar 

  51. Maglennon GA, McIntosh PB, Doorbar J. Immunosuppression facilitates the reactivation of latent papillomavirus infections. J Virol. 2014;88:710–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Muñoz N, Hernandez-Suarez G, Méndez F, Molano M, Posso H, Moreno V, et al. Persistence of HPV infection and risk of high-grade cervical intraepithelial neoplasia in a cohort of Colombian women. Br J Cancer. 2009;100:1184–90.

    Article  PubMed  PubMed Central  Google Scholar 

  53. Marks MA, Castle PE, Schiffman M, Gravitt PE. Evaluation of any or type-specific persistence of high-risk human papillomavirus for detecting cervical precancer. J Clin Microbiol. 2012;50:300–6.

    Article  PubMed  PubMed Central  Google Scholar 

  54. Stanley MA. Epithelial cell responses to infection with human papillomavirus. Clin Microbiol Rev. 2012;25:215–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Kanodia S, Fahey LM, Kast WM. Mechanisms used by human papillomaviruses to escape the host immune response. Curr Cancer Drug Targets. 2007;7:79–89.

    Article  CAS  PubMed  Google Scholar 

  56. Li S, Labrecque S, Gauzzi MC, Cuddihy AR, Wong AH, Pellegrini S, et al. The human papilloma virus (HPV)-18 E6 oncoprotein physically associates with Tyk2 and impairs Jak-STAT activation by interferon-alpha. Oncogene. 1999;18:5727–37.

    Article  CAS  PubMed  Google Scholar 

  57. Nees M, Geoghegan JM, Hyman T, Frank S, Miller L, Woodworth CD. Papillomavirus type 16 oncogenes downregulate expression of interferon-responsive genes and upregulate proliferation-associated and NF-kappaB-responsive genes in cervical keratinocytes. J Virol. 2001;75:4283–96.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Perea SE, Massimi P, Banks L. Human papillomavirus type 16 E7 impairs the activation of the interferon regulatory factor-1. Int J Mol Med. 2000;5:661–6.

    CAS  PubMed  Google Scholar 

  59. Um SJ, Rhyu JW, Kim EJ, Jeon KC, Hwang ES, Park JS. Abrogation of IRF-1 response by high-risk HPV E7 protein in vivo. Cancer Lett. 2002;179:205–12.

    Article  CAS  PubMed  Google Scholar 

  60. Caberg JH, Hubert PM, Begon DY, Herfs MF, Roncarati PJ, Boniver JJ, et al. Silencing of E7 oncogene restores functional E-cadherin expression in human papillomavirus 16-transformed keratinocytes. Carcinogenesis. 2008;29:1441–7.

    Article  CAS  PubMed  Google Scholar 

  61. Matthews K, Leong CM, Baxter L, Inglis E, Yun K, Bäckström BT, et al. Depletion of Langerhans cells in human papillomavirus type 16-infected skin is associated with E6-mediated down regulation of E-cadherin. J Virol. 2003;77:8378–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Ashrafi GH, Haghshenas M, Marchetti B, Campo MS. E5 protein of human papillomavirus 16 downregulates HLA class I and interacts with the heavy chain via its first hydrophobic domain. Int J Cancer. 2006;119:2105–12.

    Article  CAS  PubMed  Google Scholar 

  63. Carter JJ, Koutsky LA, Hughes JP, Lee SK, Kuyper J, Kiviat N, et al. Comparison of human papillomavirus types 16, 18, and 6 capsid antibody responses following incident infection. J Infect Dis. 2000;181:1911–9.

    Article  CAS  PubMed  Google Scholar 

  64. Wang SS, Schiffman M, Herrero R, Carreon J, Hildesheim A, Rodriguez AC, et al. Determinants of human papillomavirus 16 serological conversion and persistence in a population-based cohort of 10 000 women in Costa Rica. Br J Cancer. 2004;91:1269–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Carter JJ, Madeleine MM, Shera K, Schwartz SM, Cushing-Haugen KL, Wipf GC, et al. Human papillomavirus 16 and 18 L1 serology compared across anogenital cancer sites. Cancer Res. 2001;61:1934–40.

    CAS  PubMed  Google Scholar 

  66. Handler MZ, Handler NS, Majewski S, Schwartz RA. Human papillomavirus vaccine trials and tribulations: clinical perspectives. J Am Acad Dermatol. 2015;73:743–56.

    Article  PubMed  Google Scholar 

  67. de Sanjose S, Diaz M, Castellsague X, Clifford G, Bruni L, Munoz N, et al. Worldwide prevalence and genotype distribution of cervical human papillomavirus DNA in women with normal cytology: a meta-analysis. Lancet Infect Dis. 2007;7:453–9.

    Article  PubMed  Google Scholar 

  68. Castellsague X, de Sanjose S, Aguado T, Louie KS, Bruni L, Munoz J, et al., editors. HPV and cervical cancer in the world. 2007 report. WHO/ICO Information Centre on HPV and Cervical Cancer (HPV Information Centre). Vaccine. 2007;25(Suppl 3):C1–224.

    Google Scholar 

  69. Clifford GM, Gallus S, Herrero R, Munoz N, Snijders PJ, Vaccarella S, et al. Worldwide distribution of human papillomavirus types in cytologically normal women in the International Agency for Research on Cancer HPV prevalence surveys: a pooled analysis. Lancet. 2005;366:991–8.

    Article  CAS  PubMed  Google Scholar 

  70. Quint WG, Pagliusi SR, Lelie N, de Villiers EM, Wheeler CM. Results of the first World Health Organization international collaborative study of detection of human papillomavirus DNA. J Clin Microbiol. 2006;44:571–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Castellsague X, Diaz M, de Sanjose S, Munoz N, Herrero R, Franceschi S, et al. Worldwide human papillomavirus etiology of cervical adenocarcinoma and its cofactors: implications for screening and prevention. J Natl Cancer Inst. 2006;98:303–15.

    Article  PubMed  Google Scholar 

  72. Parkin DM, Whelan SLFJ, Teppo L, Thomas DB. Cancer incidence in five continents, volume VIII. IARC scientific publications no. 155. Lyon: IARC Press; 2003.

    Google Scholar 

  73. Human papillomavirus testing for triage of women with cytologic evidence of low-grade squamous intraepithelial lesions: baseline data from a randomized trial. The Atypical Squamous Cells of Undetermined Significance/Low-Grade Squamous Intraepithelial Lesions Triage Study (ALTS) Group. J Natl Cancer Inst. 2000;92:397–402.

    Google Scholar 

  74. Ho GY, Kadish AS, Burk RD, Basu J, Palan PR, Mikhail M, et al. HPV 16 and cigarette smoking as risk factors for high-grade cervical intra-epithelial neoplasia. Int J Cancer. 1998;78:281–5.

    Article  CAS  PubMed  Google Scholar 

  75. Ho GY, Bierman R, Beardsley L, Chang CJ, Burk RD. Natural history of cervicovaginal papillomavirus infection in young women. N Engl J Med. 1998;338:423–8.

    Article  CAS  PubMed  Google Scholar 

  76. Clifford GM, Smith JS, Plummer M, Munoz N, Franceschi S. Human papillomavirus types in invasive cervical cancer worldwide: a meta-analysis. Br J Cancer. 2003;88:63–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Bhatla N, Lal N, Bao YP, Ng T, Qiao YL. A meta-analysis of human papillomavirus type-distribution in women from South Asia: implications for vaccination. Vaccine. 2008;26(23):2811–7.

    Article  PubMed  Google Scholar 

  78. World Health Organization. Human papilloma virus and related cancers summary report update. 3rd ed. Geneva: WHO; 2010.

    Google Scholar 

  79. Berlin Grace VM. HPV type 18 is more oncopotent than HPV16 in uterine cervical carcinogenesis although HPV16 is the prevalent type in Chennai, India. Indian J Cancer. 2009;46:203e7.

    Article  Google Scholar 

  80. Franceschi S, Rajkumar R, Snijders PJ, Arslan A, Mahé C, Plummer M, et al. Papillomavirus infection in rural women in southern India. Br J Cancer. 2005;92:601e6.

    Google Scholar 

  81. Duttagupta C, Sengupta S, Roy M, Sengupta D, Bhattacharya P, Laikangbam P, et al. Are Muslim women less susceptible to oncogenic human papilloma virus infection? A study from the rural eastern India. Int J Gynecol Cancer. 2004;14:293–e303.

    Article  CAS  PubMed  Google Scholar 

  82. Senapati R, Nayak B, Kar SK, Dwibedi B. HPV genotypes distribution in Indian women with and without cervical carcinoma: implication for HPV vaccination program in Odisha, Eastern India. BMC Infect Dis. 2017;17:30.

    Article  PubMed  PubMed Central  Google Scholar 

  83. Laikangbam P, Sengupta S, Bhattacharya P, Duttagupta C, Dhabali Singh T, Verma Y, et al. A comparative profile of the prevalence and age distribution of human papillomavirus type 16/18 infections among three states of India with focus on Northeast India. Int J Gynecol Cancer. 2007;17:107–17.

    Article  CAS  PubMed  Google Scholar 

  84. Schellekens MC, Dijkman A, Aziz MF, Siregar B, Cornain S, Kolkman-Uljee S, et al. Single and multiple HPV types in cervical carcinomas in Jakarta, Indonesia. Gynecol Oncol. 2004;93:49–53.

    Article  PubMed  Google Scholar 

  85. Ngelangel C, Munoz N, Bosch FX, Limson GM, Festin MR, Deacon J, et al. Causes of cervical cancer in the Philippines: a case-control study. J Natl Cancer Inst. 1998;90:43–9.

    Article  CAS  PubMed  Google Scholar 

  86. Chicharen S, Herrero R, Munoz N, Bosch FX, Jacobs MV, Deacon J, et al. Risk factors for cervical cancer in Thailand: a case-control study. J Natl Cancer Inst. 1998;90:50–7.

    Article  Google Scholar 

  87. Sharma K, Kathait A, Jain A, Kujur K, Raghuwanshi S, Bharti AC, et al. Higher prevalence of human papillomavirus infection in adolescent and young adult girls belonging to different Indian tribes with varied socio-sexual lifestyle. PLoS One. 2015;10:e0125693.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  88. Hussain S, Bharadwaj M, Nasare V, Kumari M, Sharma S, Hedau S, et al. Human papillomavirus infection among young adolescents in India: impact of vaccination. J Med Virol. 2012;84:298–305.

    Article  PubMed  Google Scholar 

  89. Prusty BK, Kumar A, Arora R, Batra S, Das BC. Human papillomavirus (HPV) DNA detection in self-collected urine. Int J Gynaecol Obstet. 2005;90:223–7.

    Article  CAS  PubMed  Google Scholar 

  90. Thilagavathi A, Shanmughapriya S, Vinodhini K, Das BC, Natarajaseenivasan K. Prevalence of human papillomavirus (HPV) among college going girls using self collected urine samples from Tiruchirappalli, Tamilnadu. Arch Gynecol Obstet. 2012;286:1483–6.

    Article  CAS  PubMed  Google Scholar 

  91. Castellsagué X, Muñoz N. Chapter 3: cofactors in human papillomavirus carcinogenesis — role of parity, oral contraceptives, and tobacco smoking. J Natl Cancer Inst Monogr. 2003;31:20–8.

    Article  Google Scholar 

  92. Lacey JV Jr, Brinton LA, Abbas FM, Barnes WA, Gravitt PE, Greenberg MD, et al. Oral contraceptives as risk factors for cervical adenocarcinomas and squamous cell carcinomas. Cancer Epidemiol Biomark Prev. 1999;8:1079–85.

    Google Scholar 

  93. Hildesheim A, Herrero R, Castle PE, Wacholder S, Bratti MC, Sherman ME, et al. HPV co-factors related to the development of cervical cancer: results from a population-based study in Costa Rica. Br J Cancer. 2001;84:1219–26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Moreno V, Bosch FX, Munoz N, Meijer CJ, Shah KV, Walboomers JM, et al. Effect of oral contraceptives on risk of cervical cancer in women with human papillomavirus infection: the IARC multicentric case–control study. Lancet. 2002;359:1085–92.

    Article  CAS  PubMed  Google Scholar 

  95. Moodley M, Moodley J, Chetty R, Herrington CS. The role of steroid contraceptive hormones in the pathogenesis of invasive cervical cancer: a review. Int J Gynecol Cancer. 2003;13:103–10.

    Article  CAS  PubMed  Google Scholar 

  96. Munoz N, Franceschi S, Bosetti C, Moreno V, Herrero R, Smith JS, et al. Role of parity and human papillomavirus in cervical cancer: the IARC multicentric case–control study. Lancet. 2002;359:1093–101.

    Article  PubMed  Google Scholar 

  97. Autier P, Coibion M, Huet F, Grivegnee AR. Transformation zone location and intraepithelial neoplasia of the cervix uteri. Br J Cancer. 1996;74:488–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Sethi S, Muller M, Schneider A, Blettner M, Smith E, Turek L, et al. Serologic response to the E4, E6, and E7 proteins of human papillomavirus type 16 in pregnant women. Am J Obstet Gynecol. 1998;178:360–4.

    Article  CAS  PubMed  Google Scholar 

  99. Kjaer SK, van den Brule AJC, Bock JE, Poll PA, Engholm G, Sherman ME, et al. Human papillomavirus — the most significant risk determinant of cervical intraepithelial neoplasia. Int J Cancer. 1996;65:601–6.

    Article  CAS  PubMed  Google Scholar 

  100. Olsen AO, Dillner J, Skrondal A, Magnus P. Combined effect of smoking and human papillomavirus type 16 infection in cervical carcinogenesis. Epidemiology. 1998;9:346–9.

    Article  CAS  PubMed  Google Scholar 

  101. Ylitalo N, Sørensen P, Josefsson A, Frisch M, Sparén P, Pontén J, et al. Smoking and oral contraceptives as risk factors for cervical carcinoma in situ. Int J Cancer. 1999;81:357–65.

    Article  CAS  PubMed  Google Scholar 

  102. Plummer M, Herrero R, Franceschi S, Meijer CJLM, Snijders P, Bosch FX, et al. Smoking and cervical cancer: pooled analysis of the IARC multi-centric case–control study. Cancer Causes Control. 2003;14:805–14.

    Article  PubMed  Google Scholar 

  103. Giuliano AR, Harris R, Sedjo RL, Baldwin S, Roe D, Papenfuss MR, et al. Incidence, prevalence, and clearance of type-specific human papillomavirus infections: the young women’s health study. J Infect Dis. 2002;186:462–9.

    Article  PubMed  Google Scholar 

  104. Minkoff H, Feldman JG, Strickler HD, Watts DH, Bacon MC, Levine A, et al. Relationship between smoking and human papillomavirus infections in HIV-infected and -uninfected women. J Infect Dis. 2004;189:1821–8.

    Article  PubMed  Google Scholar 

  105. Prokopczyk B, Cox JE, Hoffmann D, Waggoner SE. Identification of tobacco-specific carcinogen in the cervical mucus of smokers and non-smokers. J Natl Cancer Inst. 1997;89:868–73.

    Article  CAS  PubMed  Google Scholar 

  106. Poppe WA, Ide PS, Drijkoningen MP, Lauweryns JM, Van Assche FA. Tobacco smoking impairs the local immunosurveillance in the uterine cervix. An immunohistochemical study. Gynecol Obstet Investig. 1995;39:34–8.

    Article  CAS  Google Scholar 

  107. Safaeian M, Quint K, Schiffman M, Rodriguez AC, Wacholder S, Herrero R, et al. Chlamydia trachomatis and risk of prevalent and incident cervical premalignancy in a population-based cohort. J Natl Cancer Inst. 2010;102:1794–804.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Zhu H, Shen Z, Luo H, Zhang W, Zhu X. Chlamydia trachomatis infection-associated risk of cervical Cancer: a Meta-analysis. Medicine (Baltimore). 2016;95:e3077.

    Article  Google Scholar 

  109. Kelly H, Weiss HA, Benavente Y, de Sanjose S, Mayaud P, ART and HPV Review Group. Association of antiretroviral therapy with high-risk human papillomavirus, cervical intraepithelial neoplasia, and invasive cervical cancer in women living with HIV: a systematic review and meta-analysis. Lancet HIV. 2018;5:e45–58.

    Article  PubMed  Google Scholar 

  110. Bruni L, Barrionuevo-Rosas L, Albero G, Serrano B, Mena M, Gómez D, et al. ICO/IARC Information Centre on HPV and Cancer (HPVInformation Centre). Human papillomavirus and related diseases in the world. Summary report 27 July 2017. [Assessed on 18 March 2018].

    Google Scholar 

  111. Bruni L, Barrionuevo-Rosas L, Albero G, Serrano B, Mena M, Gómez D, et al. ICO/IARC Information Centre on HPV and Cancer (HPV Information Centre). Human papillomavirus and related diseases in India. Summary report 27 July 2017. [Assessed on 18 March 2018].

    Google Scholar 

  112. Darragh TM, Colgan TJ, Cox JT, Heller DS, Henry MR, Luff RD, et al. The lower anogenital squamous terminology standardization project for HPV-associated lesions: background and consensus recommendations from the College of American Pathologists and the American Society for Colposcopy and Cervical Pathology. Arch Pathol Lab Med. 2012;136:1266–97.

    Article  PubMed  Google Scholar 

  113. Villa LL, Denny L. Methods for detection of HPV infection and its clinical utility. Int J Gyn Obst. 2006;94:71–80.

    Article  Google Scholar 

  114. Shen-Gunther J, Yu X. HPV molecular assays: defining analytical and clinical performance characteristics for cervical cytology specimens. Gynecol Oncol. 2011;123:263–71.

    Article  CAS  PubMed  Google Scholar 

  115. Hwang SJ, Shroyer KR. Biomarkers of cervical dysplasia and carcinoma. J Oncol. 2012;2012:507286.

    Article  PubMed  Google Scholar 

  116. Bozzetti M, Nonnenmacher B, Mielzinska II, Villa L, Lorincz A, Breitenbach VV, et al. Comparison between hybrid capture II and polymerase chain reaction results among women at low risk for cervical cancer. Ann Epidemiol. 2000;10:466.

    Article  CAS  PubMed  Google Scholar 

  117. Einstein MH, Martens MG, Garcia FA, Ferris DG, Mitchell AL, Day SP, et al. Clinical validation of the Cervista HPV HR and 16/18 genotyping tests for use in women with ASC-US cytology. Gynecol Oncol. 2010;118:116–22.

    Article  PubMed  Google Scholar 

  118. Bartholomew DA, Luff RD, Quigley NB, Curtis M, Olson MC. Analytical performance of Cervista HPV 16/18 genotyping test for cervical cytology samples. J Clin Virol. 2011;51:38–43.

    Article  CAS  PubMed  Google Scholar 

  119. Kocjan BJ, Seme K, Poljak M. Comparison of the Abbott real time high risk HPV test and INNO-LiPA HPV genotyping extra test for the detection of human papillomaviruses in formalin-fixed, paraffinembedded cervical cancer specimens. J Virol Methods. 2011;175:117–9.

    Article  CAS  PubMed  Google Scholar 

  120. Roberts I, Ng G, Foster N, Stanley M, Herdman MT, Pett MR, et al. Critical evaluation of HPV16 gene copy number quantification by SYBR green PCR. BMC Biotechnol. 2008;8:57.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  121. Choi YJ, Park JS. Clinical significance of human papillomavirus genotyping. J Gynecol Oncol. 2016;27:e21.

    Article  PubMed  CAS  Google Scholar 

  122. WHO, UN Population Fund. Preparing for the introduction of HPV vaccine: policy and programme guideance for countries. Geneva: WHO; 2006.

    Google Scholar 

  123. Meites E, Kempe A, Markowitz LE. Use of a 2-dose schedule for human papillomavirus vaccination—updated recommendations of the advisory committee on immunization practices. MMWR Morb Mortal Wkly Rep. 2016;65:1405–8.

    Article  PubMed  Google Scholar 

  124. Markowitz LE, Dunne EF, Saraiya M, Chesson HW, Curtis CR, Gee J, et al. Human papillomavirus vaccination: recommendations of the advisory committee on immunization practices (ACIP). MMWR Recomm Rep. 2014;63:1–30.

    PubMed  Google Scholar 

  125. Petrosky E, Bocchini JA Jr, Hariri S, Chesson H, Curtis CR, Saraiya M, et al. Use of 9-valent human papillomavirus (HPV) vaccine: updated HPV vaccination recommendations of the advisory committee on immunization practices. MMWR Morb Mortal Wkly Rep. 2015;64:300–4.

    PubMed  PubMed Central  Google Scholar 

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Bharani, V., Kumar, R., Bharani, B. (2019). HPV Infection and Gynecological Cancers. In: Mehta, S., Singla, A. (eds) Preventive Oncology for the Gynecologist. Springer, Singapore. https://doi.org/10.1007/978-981-13-3438-2_32

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