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The life cycle, natural history, and immunology of human papillomaviruses

Philip E Castle, PhD, MPH
Section Editor
Martin S Hirsch, MD
Deputy Editor
Allyson Bloom, MD


Human papillomaviruses (HPV) are highly prevalent, species- and tissue-specific DNA viruses that infect epithelial cells [1,2]. Persistent viral infection with carcinogenic HPV genotypes causes virtually all cancer of the cervix [3-5]. Carcinogenic HPV infections also cause many cancers of the anus, vagina, vulva, penis, and oropharynx [6-8].

Cervical cancer is the third most common cancer in women worldwide [5,9]. Although Pap testing/cytologic screening has reduced the incidence of cervical cancer by 70 percent or more where it has been effectively implemented, cervical cancer remains a leading cause of death in countries without effective screening programs [10]. (See "Invasive cervical cancer: Epidemiology, risk factors, clinical manifestations, and diagnosis".)

Based on the etiologic link between persistent carcinogenic HPV infection of the cervix and cervical cancer [3,4,11] and its immediate precursor lesions [12], one approach for the prevention of cervical disease is HPV vaccination [13]. This topic will review the life cycle, natural history, and immune response to HPV. (See "Epidemiology of human papillomavirus infections" and "Virology of human papillomavirus infections and the link to cancer".)


Over 40 mucosal HPV genotypes infect the lower female genital tract. Approximately 15 HPV types can cause all cervical cancer worldwide and are known as carcinogenic, high-risk, or cancer-associated HPV types [5]. The carcinogenic genotypes of HPV16 and HPV18, which are targeted by the current versions of the HPV vaccine, cause approximately 70 percent of all cervical cancers worldwide [14].

Productive viral infections lead to cervical abnormalities that are classified according to specimen (eg, cytology or histology) and by severity (eg, mild, moderate, or severe). Mild and morphologic changes that are the result of production HPV infections are classified as cytologic low-grade squamous intraepithelial lesion [LSIL] or histologic cervical intraepithelial neoplasia grade 1 [CIN1], whereas cervical precancerous lesions are classified as cytologic high-grade squamous intraepithelial lesion [HSIL] or histologic CIN2 or CIN3 [CIN2/3]. (See "Cervical intraepithelial neoplasia: Terminology, incidence, pathogenesis, and prevention".)


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Literature review current through: Apr 2017. | This topic last updated: Apr 17, 2015.
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