Human papillomavirus overview

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Seyedmahdi Pahlavani, M.D. [2],Aysha Anwar, M.B.B.S[3]


Papillomaviruses are a diverse group of DNA-based viruses that infect the skin and mucous membranes of humans and a variety of animals. Over 100 different human papillomavirus (HPV) types have been identified. Some HPV types may cause condylomas (skin warts) while others may cause a subclinical infection resulting in precancerous lesions. All HPVs are transmitted by skin-to-skin contact. A group of about 30-40 HPVs is typically transmitted through sexual contact and infect the anogenital region. Some sexually transmitted HPVs -- types 6, 11, may cause genital warts. However, other HPV types which may infect the genitals do not to cause any noticeable signs of infection.

Persistent infection with a subset of about 13 so-called "high-risk" sexually transmitted HPVs, including types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68 — different from the ones that cause warts — may lead to the development of cervical intraepithelial neoplasia (CIN), vulvar intraepithelial neoplasia (VIN), penile intraepithelial neoplasia (PIN), and/or anal intraepithelial neoplasia (AIN). These are precancerous lesions and can progress to invasive cancer. HPV infection is a necessary factor in the development of nearly all cases of cervical cancer.[1]

Historical Perspective

The fact that prostitutes have much higher rates of cervical cancer than nuns was a key early observation leading researchers to speculate about a causal link between sexually transmitted HPVs and cervical cancer.[2]


Human papilloma virus may have different presentations depending on the anatomical region of involvement and the virus type. Mainly it is classified to cutaneous, anogenital and other mucosal surfaces. Currently, 210 different types of HPV have been discovered and the number keeps increasing.[3][4] Clinical manifestations depend on which HPV type involve which anatomic area.[5][6]


Human papilloma virus is usually transmitted via the sexual route to the human host.[7] HPV life cycle is linked to epithelial differentiation and maturation of host keratinocytes, with transcription of specific gene products at every level.[8][9] The pathogenesis of HPV infection causing cancer is mainly linked to high-risk types of HPV (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68). E6 and E7 protein products of HPV interact with two important cell cycle regulatory proteins, P53 and Rb proteins of the host cell, causing unchecked cellular replication accumulating mutations leading to cancer.[10][11][12]

Epidemiology and Demographics

Genital HPV infection is very common, with estimates suggesting that more than 50% of women will become infected with one or more of the sexually transmitted HPV types at some point during adulthood.[13]

Risk factors

Common risk factors for anogenital HPV infection are number of sex partners, having a new partner, duration of being sexually active, vaginal delivery and multiple deliveries. Close contact is the most potent factor for cutaneous infection.


High-risk HPV types are associated with 70% of cervical cancers in females having persistent infection.[14] Due to this strong association between HPV and cervical cancer, cervical cancer screening is recommended in all females from age 21. According to the US Preventive Services Task Force (USPSTF), specific screening guidelines for cervical cancer includes screening all females from age 21 to 65 for cervical cancer.[15][16]

Natural history, Complications, and Prognosis

Most infections with HPV are subclinical, asymptomatic and resolves without any complications in immunocompetent individuals. Time to develop symptoms and signs is not well defined but it may take 3 weeks to 3 months for genital warts, several months to years for cellular abnormalities (metaplasia and dysplasia) and years for development of cancers. 90% of infections resolve within 2 years due to host immune response.[17]Persistent HPV infection is associated with risk factors such as multiple sexual partners, alcohol consumption, immunosuppression, older age, and multiple types of HPV detected previously. Without treatment, persistent infection with low-risk types (low-grade intraepithelial lesions) may resolve spontaneously or persist and proliferate as warty lesions. However, high-risk HPV types (16,18,31,32) may lead to high-grade intraepithelial lesions which ultimately to carcinoma(cervical, anal, vaginal, vulvar, penile and oropharyngeal).[18][19][20][14]Prognosis of HPV infection depends primarily on the type of HPV causing infection.[21][22][23][24][25]


History and physical examination

Detailed history about sexual activities and partners must be taken from every patient with anogenital involvement. Symptoms are mostly related to skin irritation and mucosal surface involvement. The hallmark of cutaneous involvement is pruritus however, the majority of the people acquiring HPV are asymptomatic. The clinical manifestation of HPV infection is wart that sometimes might be painful.[26]

Laboratory Findings

Certain types of sexually transmitted HPVs can cause cervical cancer. Persistent infection with one or more of about a dozen of these "high-risk" HPV types is an important factor in nearly all cases of cervical cancer. The development of HPV-induced cervical cancer is a slow process that generally takes many years. During this development phase, pre-cancerous cells can be detected by annual or semi-annual cervical cytology Papanicolaou screening, colloquially known as "Pap" smear testing. A cervical Pap smear with HPV DNA testing is used to detect cellular abnormalities and the presence of HPV. This allows targeted surgical removal of condylomatous and/or pre-cancerous lesions prior to the development of invasive cervical cancer. Although the widespread use of Pap testing has reduced the incidence and lethality of cervical cancer in developed countries, the disease still kills several hundred thousand women per year worldwide. A recently approved HPV vaccine, Gardasil, that blocks initial infection with several of the most common sexually transmitted HPV types may lead to further decreases in the incidence of HPV-induced cancer.[27]

Notable HPV types and associated diseases


There is no definitive medical treatment of HPV infection. However, treatment is mainly aimed to treat warts or precancerous lesions. Two types of medical therapy which may be considered are cytodestructive therapy and immunotherapy. No treatment is considered superior to the other. However, selection of the treatment may depend on the wart size, number of warts, anatomic site of wart, wart morphology, patient preference, cost of treatment, convenience, adverse effects. Medical therapies for human papillomavirus infection include either imiquimod, sinecatechins, or podofilox.[28][29][30][31][32][33] Surgical removal of external genital warts may be an alternative regimen to pharmacologic therapy. Surgical therapies include either tangential scissor excision, tangential shave excision, curettage, laser, or electrosurgery.[34]


Most people become infected with various cutaneous HPV types during childhood. Papillomaviruses have a sturdy outer protein shell or "capsid" that renders them capable of lingering in the environment for long periods of time. Avoiding contact with contaminated surfaces, such as the floors of communal showers or airport security lines, might reduce the risk of cutaneous HPV infection. Treating common warts soon after they first appear may also reduce the spread of the infection to additional sites.

Genital HPV infections may be distributed widely over genital skin and mucosal surfaces, and transmission can occur even when there are no overt symptoms. Several strategies should be employed to minimize the risk of developing diseases caused by genital HPVs:


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