Abstract
Human Papillomaviruses (HPV) are small deoxy-ribonucleic acid (DNA) tumor viruses with an icosahedral virion structure associated with a wide spectrum of epithelial lesions, ranging from benign warts to invasive carcinomas. They have been difficult to study, in part because they have not yet been propagated in tissue culture. Fortunately, advances in molecular biology have allowed characterization of HPV genomes and identification of some HPV gene functions. In addition to their clinical importance, HPV represent an important tool for exploring virus-cell interactions, gene expression, cellular differentiation, and cancer. HPV infections are not only common, but also difficult to treat and prevent. Depending on the HPV type and location, the modes of HPV transmission may involve casual physical contact, sexual contact, and perinatal vertical transmission. HPV DNA genomes replicate at a low copy number in basal cells and, as most clinicians know, are difficult to eradicate. There is often a long latent period and subclinical infections, plus HPV DNA can be found in normal tissue adjacent to lesions. HPV can cause widely disseminated lesions, especially in the immuno-compromised host and in epidermodysplasia verruciformis (EV). In malignant lesions, HPV DNA is also found as fragments incorporated into the cellular genome. Unlike retroviruses such as Human Immunodeficiency Virus (HIV) that integrate into the cellular genome as part of their life cycle, HPV integration is a terminal event for viral replication. Such integration is critical, however, for viral-induced abnormal cell growth. Perhaps the most important implication of some ano-genital cancers is that they may be preventable. The data overwhelmingly suggests that avoidance of exposure to HPV, via abstinence or monogamy in both partners markedly reduces the risk of cervical cancer. A more realistic goal, however, is prevention of HPV transmission by the use of barrier method contraceptives, which may be protective against development of cervical carcinoma as reported byCripe (Pediatr Infect Dis J 9:836–844, 1990). Infection with HPV is the most common STD, afflicting approximately 80% of the population. HPV infection is an essential factor in cervical carcinogenesis and cervical carcinoma the second most common cause of cancer among women worldwide. In addition to cervical cancer, other malignancies in both men and women such as esophageal, oropharyngeal, and anal cancer have been causally associated with this virus. Other gender-specific HPV-related cancers include penile, vulvar, and vaginal cancer. Recent evidence also points to a possible role of other HPV infections in squamous cell carcinomas (SCC) of the skin. During the past 20 years, several types of HPV have been identified that cause specific types of cancers. The etiology of cancer of the cervix has been linked to several types of HPV, with a high preponderance of HPV-16. HPV-16 is the most common HPV type associated with a malignant phenotype regardless of organ of origin. HPV-16, together with HPV-18, accounts for approximately 70% of cervical cancers. Other non-oncogenic HPV types, including HPV types 6 and 11, are associated with over 90% of benign HPV-related lesions such as genital warts and juvenile respiratory papillomatosis as reported by Monk and Tewari (Gynecol Oncol 107:S6–S13, 2007).
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Ambros RA, Kurman RJ (1990) Current concepts in the relationship of human papillomavirus infection to the pathogenesis and classification of precancerous squamous lesions of the uterine cervix. Semin Diagn Pathol 7:158–172
Arena S, Marconi M, Ubertosi M et al (2002) HPV and pregnancy: diagnostic methods, transmission and evolution. Minerva Ginecol 54:225–237
Arends MJ, Buckley CH, Wells M (1998) Aetiology, pathogenesis, and pathology of cervical neoplasia. J Clin Pathol 51:96–103
Ault KA (2006) Epidemiology and natural history of human papillomavirus infections in the female genital tract. Infect Dis Obstet Gynecol 2006 Suppl:40470
Bartolozzi G, Bona G, Ciofi M et al (2007) Human papillomavirus vaccination. Consensus conference in pediatric age. Minerva Pediatr 59:165–182
Bodily J, Laimins LA (2011) Persistence of human papillomavirus infection: keys to malignant progression. Trends Microbiol 19:33–39
Bornstein J, Rahat MA, Abramovici H (1995) Etiology of cervical cancer: current concepts. Obstet Gynecol Surv 50:146–154
Brescia RJ, Jenson AB, Lancaster WD et al (1986) The role of human papillomaviruses in the pathogenesis and histologic classification of precancerous lesions of the cervix. Hum Pathol 17:552–559
Brinton LA (1992) Epidemiology of cervical cancer – overview. IARC Sci Publ 119:3–23
Brinton LA, Fraumeni JF Jr (1986) Epidemiology of uterine cervical cancer. J Chronic Dis 39:1051–1065
Bruni L, Diaz M, Castellsagué X et al (2010) Cervical human papillomavirus prevalence in 5 continents: meta-analysis of 1 million women with normal cytological findings. J Infect Dis 202:1789–1799
Butterworth CE Jr (1992) Effect of folate on cervical cancer. Synergism among risk factors. Ann N Y Acad Sci 669:293–299
Cardiff RD, Borowsky AD (2010) Precancer: sequentially acquired or predetermined? Toxicol Pathol 38:171–179
Cason J, Rice P, Best JM (1998) Transmission of cervical cancer-associated human papillomaviruses from mother to child. Intervirology 41:213–218
Castellsagué X, Díaz M, de Sanjosé S et al (2006) Worldwide human papillomavirus etiology of cervical adenocarcinoma and its co-factors: implications for screening and prevention. J Natl Cancer Inst 98:303–315
Cox JT (1995) Epidemiology of cervical intraepithelial neoplasia: the role of human papillomavirus. Baillieres Clin Obstet Gynaecol 9:1–37
Crum CP, Levine RU (1984) Human papillomavirus infection and cervical neoplasia: new perspectives. Int J Gynecol Pathol 3:376–388
Crum CP, McLachlin CM (1995) Cervical intraepithelial neoplasia. J Cell Biochem Suppl 23:71–79
de Sanjosé S, Bosch FX, Muñoz N et al (1997) Social differences in sexual behaviour and cervical cancer. IARC Sci Publ 138:309–317
Delgado-Enciso I, Rojas-Martínez A, Barrera-Saldaña HA et al (2004) Viruses: an important cause of human cancer. Rev Invest Clin 56:495–506
Deligeoroglou E, Christopoulos P, Aravantinos L et al (2009) Human papillomavirus molecular profile and mechanisms of cancerogenesis: a review. Eur J Gynaecol Oncol 30:128–132
Denis F, Hanz S, Alain S (2008) Clearance, persistence and recurrence of HPV infection. Gynecol Obstet Fertil 36:430–440
Dillner J (2000) Trends over time in the incidence of cervical neoplasia in comparison to trends over time in human papillomavirus infection. J Clin Virol 19:7–23
DiPaolo JA, Popescu NC, Woodworth CD et al (1996) Papillomaviruses and potential copathogens. Toxicol Lett 88:1–7
Ferenczy A, Franco E (2002) Persistent human papillomavirus infection and cervical neoplasia. Lancet Oncol 3:11–16
Ferenczy A, Jenson AB (1996) Tissue effects and host response. The key to the rational triage of cervical neoplasia. Obstet Gynecol Clin North Am 23:759–782
Franco EL (1992) Measurement errors in epidemiological studies of human papillomavirus and cervical cancer. IARC Sci Publ 119:181–197
Garland SM (2002) Human papillomavirus update with a particular focus on cervical disease. Pathology 34:213–224
Giannoudis A, Herrington CS (2001) Human papillomavirus variants and squamous neoplasia of the cervix. J Pathol 193:295–302
Gissmann L (1992) Human papillomaviruses and genital cancer. Semin Cancer Biol 3:253–261
Gray SH, Walzer TB (2004) New strategies for cervical cancer screening in adolescents. Curr Opin Pediatr 16:344–349
Guido R (2004) Guidelines for screening and treatment of cervical disease in the adolescent. J Pediatr Adolesc Gynecol 17:303–311
Haverkos HW (2005) Multifactorial etiology of cervical cancer: a hypothesis. MedGenMed 7:57
Heard I (2005) Ano-genital lesions due to human papillomavirus infection in women. Med Mal Infect 35:302–305
Huh WK (2009) Human papillomavirus infection: a concise review of natural history. Obstet Gynecol 114:139–143
Insinga RP, Dasbach EJ, Elbasha EH (2009) Epidemiologic natural history and clinical management of Human Papillomavirus (HPV) Disease: a critical and systematic review of the literature in the development of an HPV dynamic transmission model. BMC Infect Dis 9:119
Jenson HB (2009) Human papillomavirus vaccine: a paradigm shift for pediatricians. Curr Opin Pediatr 21:112–121
Jenson AB, Kurman RJ, Lancaster WD (1991) Tissue effects of and host response to human papillomavirus infection. Dermatol Clin 9:203–209
Kaminski PF, Lyon DS, Sorosky JI et al (1992) Significance of atypical cervical cytology in pregnancy. Am J Perinatol 9:340–343
Kjaer SK, Jensen OM (1992) Comparison studies of HPV detection in areas at different risk for cervical cancer. IARC Sci Publ 119:243–249
Kollar LM, Kahn JA (2008) Education about human papillomavirus and human papillomavirus vaccines in adolescents. Curr Opin Obstet Gynecol 20:479–483
Koss LG (1987) Cytologic and histologic manifestations of human papillomavirus infection of the female genital tract and their clinical significance. Cancer 60:1942–1950
Leung AK, Kellner JD, Davies HD (2005) Genital infection with human papillomavirus in adolescents. Adv Ther 22:187–197
Li N, Franceschi S, Howell-Jones R et al (2011) Human papillomavirus type distribution in 30,848 invasive cervical cancers worldwide: variation by geographical region, histological type and year of publication. Int J Cancer 128:927–935
Lillo FB (2005) Human papillomavirus infection and its role in the genesis of dysplastic and neoplastic lesions of the squamous epithelia. New Microbiol 28:111–118
Longworth MS, Laimins LA (2004) Pathogenesis of human papillomaviruses in differentiating epithelia. Microbiol Mol Biol Rev 68:362–372
Mammas IN, Sourvinos G, Spandidos DA (2009) Human papillomavirus (HPV) infection in children and adolescents. Eur J Pediatr 168:267–273
McCance DJ (1988) Human papillomavirus (HPV) infections in the aetiology of cervical cancer. Cancer Surv 7:499–506
Monsonego J (1995) Cellular and molecular pathogenesis of cancer of the cervix. Contracept Fertil Sex 23:731–740
Moore TO, Moore AY, Carrasco D et al (2001) Human papillomavirus, smoking, and cancer. J Cutan Med Surg 5:323–328
Morrison EA (1994) Natural history of cervical infection with human papillomaviruses. Clin Infect Dis 18:172–180
Moscicki AB (1992) Human papillomavirus infections. Adv Pediatr 39:257–281
Moscicki AB (1996) Genital HPV infections in children and adolescents. Obstet Gynecol Clin North Am 23:675–697
Moscicki AB (2005a) Cervical cytology testing in teens. Curr Opin Obstet Gynecol 17:471–475
Moscicki AB (2005b) Impact of HPV infection in adolescent populations. J Adolesc Health 37:S3–S9
Moscicki AB (2007) HPV infections in adolescents. Dis Markers 23:229–234
Moscicki AB (2008a) Conservative management of adolescents with abnormal cytology and histology. J Natl Compr Canc Netw 6:101–106
Moscicki AB (2008b) Management of adolescents who have abnormal cytology and histology. Obstet Gynecol Clin North Am 35:633–643
Mougin C, Mo L, Dalstein V (2006) Natural history of papillomavirus infections. Rev Prat 56:1883–1889
Muñoz N, Bosch FX (1992) HPV and cervical neoplasia: review of case–control and cohort studies. IARC Sci Publ 119:251–261
Murthy NS, Mathew A (2000) Risk factors for pre-cancerous lesions of the cervix. Eur J Cancer Prev 9:5–14
Pagliusi SR (2007) HPV technologies advancing public health: discussion of recent evidence. Coll Antropol 31(Suppl 2):55–60
Penna C, Fallani MG, Cariti G et al (1989) Viral infections and neoplasms of the uterine cervix. Minerva Ginecol 41:9–15
Piyathilake CJ (2007) Update on micronutrients and cervical dysplasia. Ethn Dis 17:S2-14-7
Plummer M, Herrero R, Franceschi S et al (2003) Smoking and cervical cancer: pooled analysis of the IARC multi-centric case–control study. Cancer Causes Control 14:805–814
Pontén J, Guo Z (1998) Precancer of the human cervix. Cancer Surv 32:201–229
Potischman N, Brinton LA (1996) Nutrition and cervical neoplasia. Cancer Causes Control 7:113–126
Prétet JL, Charlot JF, Mougin C (2007) Virological and carcinogenic aspects of HPV. Bull Acad Natl Med 191:611–623
Regan DG, Philp DJ, Waters EK (2010) Unresolved questions concerning human papillomavirus infection and transmission: a modelling perspective. Sex Health 7:368–375
Reid R (1983) Genital warts and cervical cancer. II. Is human papillomavirus infection the trigger to cervical carcinogenesis? Gynecol Oncol 15:239–252
Reid R (1987) Human papillomaviral infection. The key to rational triage of cervical neoplasia. Obstet Gynecol Clin North Am 14:407–429
Richart RM (1987) Causes and management of cervical intraepithelial neoplasia. Cancer 60:1951–1959
Richart RM, Wright TC Jr (1991) Pathology of the cervix. Curr Opin Obstet Gynecol 3:561–567
Romney SL, Palan PR, Basu J et al (1995) Nutrient antioxidants in the pathogenesis and prevention of cervical dysplasias and cancer. J Cell Biochem Suppl 23:96–103
Schiffman MH, Brinton LA (1995) The epidemiology of cervical carcinogenesis. Cancer 76:1888–1901
Schiffman M, Castle PE, Jeronimo J et al (2007) Human papillomavirus and cervical cancer. Lancet 370:890–907
Schneider A (1993) Pathogenesis of genital HPV infection. Genitourin Med 69:165–173
Schoell WM, Janicek MF, Mirhashemi R (1999) Epidemiology and biology of cervical cancer. Semin Surg Oncol 16:203–211
Selleret L, Mathevet P (2008) Precancerous cervical lesions during pregnancy: diagnostic and treatment. J Gynecol Obstet Biol Reprod (Paris) 37(Suppl 1):S131–S138
Simon P, Roumeguere T, Christophe Noël J (2010) Human papillomavirus infection in couples with female low-grade intraepithelial cervical lesion. Eur J Obstet Gynecol Reprod Biol 153:8–11
Slama J, Fischerova D, Pinkavova I et al (2010) Human papillomavirus DNA presence in pelvic lymph nodes in cervical cancer. Int J Gynecol Cancer 20:126–132
Stanley M (2010) Pathology and epidemiology of HPV infection in females. Gynecol Oncol 117:S5–S10
Stanley MA, Pett MR, Coleman N (2007) HPV: from infection to cancer. Biochem Soc Trans 35:1456–1460
Steben M, Duarte-Franco E (2007) Human papillomavirus infection: epidemiology and pathophy-siology. Gynecol Oncol 107:S2–S5
Steenbergen RD, de Wilde J, Wilting SM et al (2005) HPV-mediated transformation of the anogenital tract. J Clin Virol 32(Suppl 1):S25–S33
Syrjänen KJ (1986) Human papillomavirus (HPV) infections of the female genital tract and their associations with intraepithelial neoplasia and squamous cell carcinoma. Pathol Annu 21(Pt 1):53–89
Syrjänen KJ (1987) Biology of human papillomavirus (HPV) infections and their role in squamous cell carcinogenesis. Med Biol 65:21–39
Syrjänen KJ (1989) Epidemiology of human papillomavirus (HPV) infections and their associations with genital squamous cell cancer. Review article. APMIS 97:957–970
Syrjänen KJ (1996) Spontaneous evolution of intraepithelial lesions according to the grade and type of the implicated human papillomavirus (HPV). Eur J Obstet Gynecol Reprod Biol 65:45–53
Syrjänen K (2007) Mechanisms and predictors of high-risk human papillomavirus (HPV) clearance in the uterine cervix. Eur J Gynaecol Oncol 28:337–351
Syrjänen S, Puranen M (2000) Human papillomavirus infections in children: the potential role of maternal transmission. Crit Rev Oral Biol Med 11:259–274
Syrjänen KJ, Syrjänen SM (1985) Human papillomavirus (HPV) infections related to cervical intraepithelial neoplasia (CIN) and squamous cell carcinoma of the uterine cervix. Ann Clin Res 17:45–56
Syrjänen K, Syrjänen S (1990) Epidemiology of human papillomavirus infections and genital neoplasia. Scand J Infect Dis Suppl 69:7–17
Tranbaloc P (2008) Natural history of precursor lesions of cervical cancer. Gynecol Obstet Fertil 36:650–655
Trottier H, Burchell AN (2009) Epidemiology of mucosal human papillomavirus infection and associated diseases. Public Health Genomics 12:291–307
Trottier H, Franco EL (2006) The epidemiology of genital human papillomavirus infection. Vaccine 24(Suppl 1):S1–S15
Tscherne G (1997) Female genital tract malignancies during puberty. Uterine and cervical malignancies. Ann NY Acad Sci 816:331–337
Veldhuijzen NJ, Snijders PJ, Reiss P et al (2010) Factors affecting transmission of mucosal human papillomavirus. Lancet Infect Dis 10:862–874
Vousden KH (1989) Human papillomaviruses and cervical carcinoma. Cancer Cells 1:43–50
Wacholder S (2003) Chapter 18: statistical issues in the design and analysis of studies of human papillomavirus and cervical neoplasia. J Natl Cancer Inst Monogr 31:125–130
Widdice LE, Moscicki AB (2008) Updated guidelines for papanicolaou tests, colposcopy, and human papillomavirus testing in adolescents. J Adolesc Health 43:S41–S51
Yabroff KR, Lawrence WF, King JC et al (2005) Geographic disparities in cervical cancer mortality: what are the roles of risk factor prevalence, screening, and use of recommended treatment? J Rural Health 21:149–157
Zoundi-Ouango O, Morcel K, Classe JM et al (2006) Uterine cervical lesions during pregnancy: diagnosis and management. J Gynecol Obstet Biol Reprod (Paris) 35:227–236
zur Hausen H (1989) Papillomaviruses in anogenital cancer as a model to understand the role of viruses in human cancers. Cancer Res 49:4677–4681
zur Hausen H (1990) The role of papillomaviruses in anogenital cancer. Scand J Infect Dis Suppl 69:107–111
zur Hausen H (1991) Human papillomaviruses in the pathogenesis of anogenital cancer. Virology 184:9–13
zur Hausen H (1999) Papillomaviruses in human cancers. Proc Assoc Am Physicians 111:581–587
zur Hausen H (2002) Papillomaviruses and cancer: from basic studies to clinical application. Nat Rev Cancer 2:342–350
zur Hausen H (2008) Papillomaviruses – to vaccination and beyond. Biochemistry (Mosc) 73:498–503
zur Hausen H (2009) Papillomaviruses in the causation of human cancers – a brief historical account. Virology 384:260–265
zur Hausen H, de Villiers EM (1994) Human papillomaviruses. Annu Rev Microbiol 48:427–447
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2012 Springer Science+Business Media, LLC
About this chapter
Cite this chapter
Borruto, F., Comparetto, C. (2012). Human Papillomavirus: Natural History of a Viral Infection in the Genesis of a Cancer. In: Borruto, F., De Ridder, M. (eds) HPV and Cervical Cancer. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-1988-4_2
Download citation
DOI: https://doi.org/10.1007/978-1-4614-1988-4_2
Published:
Publisher Name: Springer, New York, NY
Print ISBN: 978-1-4614-1987-7
Online ISBN: 978-1-4614-1988-4
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)