Some HPV types, such as HPV-5, may establish infections that persist for the lifetime of the individual without ever manifesting any clinical symptoms. HPV types 1 and 2 can cause common warts in some infected individuals. HPV types 6 and 11 can cause genital warts and laryngeal papillomatosis. Many HPV types are carcinogenic. The table below lists common symptoms of HPV infection and the associated strains of HPV. Disease HPV type Common warts 2, 7, 22 Plantar warts 1, 2, 4, 63 Flat warts 3, 10, 28 Anogenital warts 6, 11, 42, 44 and others Anal dysplasia (lesions) 16, 18, 31, 53, 58 Genital cancers * Highest risk: 16, 18, 31, 45 * Other high-risk: 33, 35, 39, 51, 52, 56, 58, 59 * Probably high-risk: 26, 53, 66, 68, 73, 82 Epidermodysplasia verruciformis more than 15 types Focal epithelial hyperplasia (mouth) 13, 32 Mouth papillomas 6, 7, 11, 16, 32 Oropharyngeal cancer 16 Verrucous cyst 60 Laryngeal papillomatosis 6, 11 Warts Papilloma A sample DNA test report for HPV genotype from a laboratory Skin infection ("cutaneous" infection) with HPV is very widespread. Skin infections with HPV can cause noncancerous skin growths called warts (verrucae). Warts are caused by a rapid growth of cells on the outer layer of the skin. While cases of warts have been described since the time of ancient Greece, their viral cause was not known until 1907. Skin warts are most common in childhood and typically appear and regress spontaneously over the course of weeks to months. Recurring skin warts are common. All HPVs are believed to be capable of establishing long-term "latent" infections in small numbers of stem cells present in the skin. Although these latent infections may never be fully eradicated, immunological control is thought to block the appearance of symptoms such as warts. Immunological control is HPV type-specific, meaning an individual may become resistant to one HPV type while remaining susceptible to other types. Types of warts include: * Common warts are usually found on the hands and feet, but can also occur in other areas, such as the elbows or knees. Common warts have a characteristic cauliflower-like surface and are typically slightly raised above the surrounding skin. Cutaneous HPV types can cause genital warts but are not associated with the development of cancer. * Plantar warts are found on the soles of the feet; they grow inward, generally causing pain when walking. * Subungual or periungual warts form under the fingernail (subungual), around the fingernail, or on the cuticle (periungual). They are more difficult to treat than warts in other locations. * Flat warts are most commonly found on the arms, face, or forehead. Like common warts, flat warts occur most frequently in children and teens. In people with normal immune function, flat warts are not associated with the development of cancer. Common, flat, and plantar warts are much less likely to spread from person to person. Genital warts HPV infection of the skin in the genital area is the most common sexually transmitted infection worldwide. Such infections are associated with genital or anal warts<unk> ly known as condylomata acuminata or venereal warts), and these warts are the most easily recognized sign of genital HPV infection. The strains of HPV that can cause genital warts are usually different from those that cause warts on other parts of the body, such as the hands or feet, or even the inner thighs. A wide variety of HPV types can cause genital warts, but types 6 and 11 together account for about 90% of all cases. However, in total more than 40 types of HPV are transmitted through sexual contact and can infect the skin of the anus and genitals. Such infections may cause genital warts, although they may also remain asymptomatic. The great majority of genital HPV infections never cause any overt symptoms and are cleared by the immune system in a matter of months. Moreover, people may transmit the virus to others even if they do not display overt symptoms of infection. Most people acquire genital HPV infections at some point in their lives, and about 10% of women are currently infected. A large increase in the incidence of genital HPV infection occurs at the age when individuals begin to engage in sexual activity. As with cutaneous HPVs, immunity to genital HPV is believed to be specific to a specific strain of HPV. Laryngeal papillomatosis In addition to genital warts, infection by HPV types 6 and 11 can cause a rare condition known as recurrent laryngeal papillomatosis, in which warts form on the larynx or other areas of the respiratory tract. These warts can recur frequently, may interfere with breathing, and in extremely rare cases can progress to cancer. For these reasons, repeated surgery to remove the warts may be advisable. Cancer HPV-induced cancers Virus types About a dozen HPV types (including types 16, 18, 31, and 45) are called "high-risk" types because persistent infection has been linked to cancer of the oropharynx, larynx, vulva, vagina, cervix, penis, and anus. These cancers all involve sexually transmitted infection of HPV to the stratified epithelial tissue. Individuals infected with both HPV and HIV have an increased risk of developing cervical or anal cancer. HPV type 16 is the strain most likely to cause cancer and is present in about 47% of all cervical cancers, and in many vaginal and vulvar cancers, penile cancers, anal cancers, and cancers of the head and neck. Case statistics An estimated 561,200 new cancer cases worldwide (5.2% of all new cancers) were attributable to HPV in 2002, making HPV one of the most important infectious causes of cancer. HPV-associated cancers make up over 5% of total diagnosed cancer cases worldwide, and this incidence is higher in developing countries where it is estimated to cause almost half a million cases each year. In the United States, about 30,700 cases of cancer due to HPV occur each year. +The number of HPV-associated cancers in the period of 2008–2012 in the US. Cancer area Average annual number of cases HPV attributable (estimated) HPV 16/18 attributable (estimated) Cervix 11,771 10,700 7,800 Oropharynx (men) 12,638 9,100 8,000 Oropharynx (women) 3,100 2,000 1,600 Vulva 3,554 2,400 1,700 Anus (women) 3,260 3,000 2,600 Anus (men) 1,750 1,600 1,400 Penis 1,168 700 600 Vagina 802 600 400 Rectum (women) 513 500 400 Rectum (men) 237 200 200 Total 38,793 30,700 24,600 Cancer development Genome organization of human papillomavirus type 16, one of the subtypes known to cause cervical cancer (E1-E7 early genes, L1-L2 late genes: capsid) In some infected individuals, their immune systems may fail to control HPV. Lingering infection with high-risk HPV types, such as types 16, 18, 31, and 45, can favor the development of cancer. Co-factors such as cigarette smoke can also enhance the risk of such HPV-related cancers. HPV is believed to cause cancer by integrating its genome into nuclear DNA. Some of the early genes expressed by HPV, such as E6 and E7, act as oncogenes that promote tumor growth and malignant transformation. HPV genome integration can also cause carcinogenesis by promoting genomic instability associated with alterations in DNA copy number. E6 produces a protein (also called E6) that binds to and inactivates a protein in the host cell called p53. Normally, p53 acts to prevent cell growth, and promotes cell death in the presence of DNA damage. p53 also upregulates the p21 protein, which blocks the formation of the cyclin D/Cdk4 complex, thereby preventing the phosphorylation of retinoblastoma protein (RB), and in turn, halting cell cycle progression by preventing the activation of E2F. In short, p53 is a tumor-suppressor protein that arrests the cell cycle and prevents cell growth and survival when DNA damage occurs. Thus, inactivation of p53 by E6 can promote unregulated cell division, cell growth, and cell survival, characteristics of cancer. E6 also has a close relationship with the cellular protein E6-associated protein (E6-AP), which is involved in the ubiquitin ligase pathway, a system that acts to degrade proteins. E6-AP binds ubiquitin to the p53 protein, thereby flagging it for proteosomal degradation. Squamous cell carcinoma of the skin Studies have also shown a link between a wide range of HPV types and squamous cell carcinoma of the skin. In such cases, in vitro studies suggest that the E6 protein of the HPV virus may inhibit apoptosis induced by ultraviolet light. Cervical cancer Artist's impression of cervical cancer caused by HPV. Nearly all cases of cervical cancer are associated with HPV infection, with two types, HPV16 and HPV18, present in 70% of cases. In 2012, twelve HPV types were considered carcinogenic for cervical cancer by the International Agency for Research on Cancer: 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, and 59. HPV is necessary for cervical cancer to occur. Persistent HPV infection increases the risk for developing cervical carcinoma. Individuals who have an increased incidence of these types of infection are women with HIV/AIDS, who are at a 22-fold increased risk of cervical cancer. The
medical cause of Cervical cancer
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symptom of Endometrial cancer
causes of Cervical cancer
symptom of Ovarian cancer
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