Human papillomavirus overview: Difference between revisions

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{{Human papillomavirus}}
{{Human papillomavirus}}
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==Overview==
==Overview==


[[Papillomavirus]]es are a diverse group of [[DNA virus|DNA-based viruses]] that infect the skin and [[mucous membrane]]s of humans and a variety of animals. Over 100 different '''human papillomavirus''' (HPV) types have been identified.
[[Papillomavirus]]es are a diverse group of [[DNA virus|DNA-based viruses]] that infect the [[skin]] and [[mucous membrane]]s 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|(skin warts]]) while others may cause a subclinical infection resulting in [[Precancerous|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 wart]]s. However, other HPV types which may infect the genitals do not to cause any noticeable signs of infection.


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.
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|cervical intraepithelial neoplasia (CIN)]], [[vulvar intraepithelial neoplasia]] (VIN), penile intraepithelial neoplasia (PIN), and/or anal intraepithelial neoplasia (AIN).  These are [[Precancerous|precancerous lesions]] and can progress to invasive cancer.  HPV infection is a necessary factor in the development of nearly all cases of [[cervical cancer]].<ref>{{cite journal |author=Walboomers JM, Jacobs MV, Manos MM, ''et al'' |title=Human papillomavirus is a necessary cause of invasive cervical cancer worldwide |journal=J. Pathol. |volume=189 |issue=1 |pages=12-9 |year=1999 |pmid=10451482 |doi=10.1002/(SICI)1096-9896(199909)189:1<12::AID-PATH431>3.0.CO;2-F}}</ref>


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 wart]]s. However, other HPV types which may infect the genitals do not to cause any noticeable signs of infection.
==Historical Perspective==


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]].<ref>{{cite journal |author=Walboomers JM, Jacobs MV, Manos MM, ''et al'' |title=Human papillomavirus is a necessary cause of invasive cervical cancer worldwide |journal=J. Pathol. |volume=189 |issue=1 |pages=12-9 |year=1999 |pmid=10451482 |doi=10.1002/(SICI)1096-9896(199909)189:1<12::AID-PATH431>3.0.CO;2-F}}</ref>
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]].<ref>{{cite journal |author=zur Hausen H, de Villiers EM |title=Human papillomaviruses |journal=Annu. Rev. Microbiol. |volume=48 |issue= |pages=427-47 |year=1994 |pmid=7826013}}</ref>


==Historical Perspective==
==Classification==
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.<ref name="urlReference clones at International HPV Reference Center">{{cite web |url=http://www.hpvcenter.se/html/refclones.html?%3C?php%20echo%20time();%20?%3E |title=Reference clones at International HPV Reference Center |format= |work= |accessdate=}}</ref><ref name="pmid20206957">{{cite journal |vauthors=Bernard HU, Burk RD, Chen Z, van Doorslaer K, zur Hausen H, de Villiers EM |title=Classification of papillomaviruses (PVs) based on 189 PV types and proposal of taxonomic amendments |journal=Virology |volume=401 |issue=1 |pages=70–9 |year=2010 |pmid=20206957 |pmc=3400342 |doi=10.1016/j.virol.2010.02.002 |url=}}</ref>
Clinical manifestations depend on which [[HPV]] type involve which anatomic area.<ref name="pmid2463866">{{cite journal |vauthors=Jenson AB, Kurman RJ, Lancaster WD |title=Detection of papillomavirus common antigens in lesions of skin and mucosa |journal=Clin. Dermatol. |volume=3 |issue=4 |pages=56–63 |year=1985 |pmid=2463866 |doi= |url=}}</ref><ref name="pmid25577151">{{cite journal |vauthors=Bzhalava D, Eklund C, Dillner J |title=International standardization and classification of human papillomavirus types |journal=Virology |volume=476 |issue= |pages=341–4 |year=2015 |pmid=25577151 |doi=10.1016/j.virol.2014.12.028 |url=}}</ref>


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.<ref>{{cite journal |author=zur Hausen H, de Villiers EM |title=Human papillomaviruses |journal=Annu. Rev. Microbiol. |volume=48 |issue= |pages=427-47 |year=1994 |pmid=7826013}}</ref>
==Pathophysiology==
Human papilloma virus is usually transmitted via the sexual route to the human host.<ref name="pmid18507898">{{cite journal| author=Hernandez BY, Wilkens LR, Zhu X, Thompson P, McDuffie K, Shvetsov YB et al.| title=Transmission of human papillomavirus in heterosexual couples. | journal=Emerg Infect Dis | year= 2008 | volume= 14 | issue= 6 | pages= 888-94 | pmid=18507898 | doi=10.3201/eid1406.070616 | pmc=2600292 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18507898  }} </ref> [[Human papillomavirus|HPV]] life cycle is linked to epithelial [[differentiation]] and maturation of host [[keratinocytes]], with [[transcription]] of specific gene products at every level.<ref name="pmid15753007">{{cite journal| author=Doorbar J| title=The papillomavirus life cycle. | journal=J Clin Virol | year= 2005 | volume= 32 Suppl 1 | issue=  | pages= S7-15 | pmid=15753007 | doi=10.1016/j.jcv.2004.12.006 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15753007  }} </ref><ref name="pmid23199966">{{cite journal| author=Doorbar J, Quint W, Banks L, Bravo IG, Stoler M, Broker TR et al.| title=The biology and life-cycle of human papillomaviruses. | journal=Vaccine | year= 2012 | volume= 30 Suppl 5 | issue=  | pages= F55-70 | pmid=23199966 | doi=10.1016/j.vaccine.2012.06.083 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23199966  }} </ref> The pathogenesis of [[Human papillomavirus|HPV]] infection causing cancer is mainly linked to high-risk types of [[Human papillomavirus|HPV]] (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68). E6 and E7 protein products of [[Human papillomavirus|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.<ref name="pmid20592731">{{cite journal| author=Moody CA, Laimins LA| title=Human papillomavirus oncoproteins: pathways to transformation. | journal=Nat Rev Cancer | year= 2010 | volume= 10 | issue= 8 | pages= 550-60 | pmid=20592731 | doi=10.1038/nrc2886 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20592731  }} </ref><ref name="pmid2823272">{{cite journal| author=Masuda H, Miller C, Koeffler HP, Battifora H, Cline MJ| title=Rearrangement of the p53 gene in human osteogenic sarcomas. | journal=Proc Natl Acad Sci U S A | year= 1987 | volume= 84 | issue= 21 | pages= 7716-9 | pmid=2823272 | doi= | pmc=299371 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2823272  }} </ref><ref name="pmid8380917">{{cite journal| author=Tommasino M, Adamczewski JP, Carlotti F, Barth CF, Manetti R, Contorni M et al.| title=HPV16 E7 protein associates with the protein kinase p33CDK2 and cyclin A. | journal=Oncogene | year= 1993 | volume= 8 | issue= 1 | pages= 195-202 | pmid=8380917 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8380917  }} </ref>


==Epidemiology and Demographics==
==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.<ref name="Baseman">{{cite journal |author=Baseman JG, Koutsky LA |title=The epidemiology of human papillomavirus infections |journal=J. Clin. Virol. |volume=32 Suppl 1 |issue= |pages=S16-24 |year=2005 |pmid=15753008 |doi=10.1016/j.jcv.2004.12.008}} *Note: The authors state on page S17 "Overall, these DNA-based studies, combined with measurements of type-specific antibodies against HPV capsid antigens, have shown that most (>50%) sexually active women have been infected by one or more genital HPV types at some point in time."</ref>
Genital [[Human papillomavirus|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 [[Human papillomavirus|HPV]] types at some point during adulthood.<ref name="Baseman">{{cite journal |author=Baseman JG, Koutsky LA |title=The epidemiology of human papillomavirus infections |journal=J. Clin. Virol. |volume=32 Suppl 1 |issue= |pages=S16-24 |year=2005 |pmid=15753008 |doi=10.1016/j.jcv.2004.12.008}} *Note: The authors state on page S17 "Overall, these DNA-based studies, combined with measurements of type-specific antibodies against HPV capsid antigens, have shown that most (>50%) sexually active women have been infected by one or more genital HPV types at some point in time."</ref>
 
==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.
 
==Screening==
High-risk [[Human papillomavirus|HPV]] types are associated with 70% of [[Cervical cancer|cervical cancers]] in females having persistent infection.<ref name=CDC4>http://www.cdc.gov/vaccines/pubs/pinkbook/hpv.html#epi Accessed on October 13, 2016</ref> Due to this strong association between [[Human papillomavirus|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]].<ref name="pmid22711081">{{cite journal| author=Moyer VA, U.S. Preventive Services Task Force| title=Screening for cervical cancer: U.S. Preventive Services Task Force recommendation statement. | journal=Ann Intern Med | year= 2012 | volume= 156 | issue= 12 | pages= 880-91, W312 | pmid=22711081 | doi=10.7326/0003-4819-156-12-201206190-00424 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22711081  }} </ref><ref name="pmid25302174">{{cite journal| author=McGraw SL, Ferrante JM| title=Update on prevention and screening of cervical cancer. | journal=World J Clin Oncol | year= 2014 | volume= 5 | issue= 4 | pages= 744-52 | pmid=25302174 | doi=10.5306/wjco.v5.i4.744 | pmc=4129537 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25302174  }} </ref>
==Natural history, Complications, and Prognosis==
Most infections with [[Human papillomavirus|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]].<ref name="pmid16967912">{{cite journal| author=Ault KA| title=Epidemiology and natural history of human papillomavirus infections in the female genital tract. | journal=Infect Dis Obstet Gynecol | year= 2006 | volume= 2006 Suppl | issue=  | pages= 40470 | pmid=16967912 | doi=10.1155/IDOG/2006/40470 | pmc=1581465 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16967912  }} </ref>Persistent [[Human papillomavirus|HPV]] infection is associated with risk factors such as multiple sexual partners, alcohol consumption, [[immunosupression|immunosuppression]], older age, and multiple types of [[HPV]] detected previously. Without treatment, persistent infection with low-risk types ([[CIN|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 [[CIN|high-grade intraepithelial lesions]] which ultimately to [[carcinoma]]([[Cervical cancer|cervical]], [[Colorectal cancer|anal]], [[Vaginal cancer|vaginal]], [[Vulvar cancer|vulvar]], [[Penile cancer|penile]] and [[Oropharyngeal cancer|oropharyngeal]]).<ref name="pmid15871112">{{cite journal| author=Castle PE, Schiffman M, Herrero R, Hildesheim A, Rodriguez AC, Bratti MC et al.| title=A prospective study of age trends in cervical human papillomavirus acquisition and persistence in Guanacaste, Costa Rica. | journal=J Infect Dis | year= 2005 | volume= 191 | issue= 11 | pages= 1808-16 | pmid=15871112 | doi=10.1086/428779 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15871112  }} </ref><ref name="pmid11410191">{{cite journal| author=Woodman CB, Collins S, Winter H, Bailey A, Ellis J, Prior P et al.| title=Natural history of cervical human papillomavirus infection in young women: a longitudinal cohort study. | journal=Lancet | year= 2001 | volume= 357 | issue= 9271 | pages= 1831-6 | pmid=11410191 | doi=10.1016/S0140-6736(00)04956-4 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11410191  }} </ref><ref name="pmid9459645">{{cite journal| author=Ho GY, Bierman R, Beardsley L, Chang CJ, Burk RD| title=Natural history of cervicovaginal papillomavirus infection in young women. | journal=N Engl J Med | year= 1998 | volume= 338 | issue= 7 | pages= 423-8 | pmid=9459645 | doi=10.1056/NEJM199802123380703 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9459645  }} </ref><ref name=CDC4>http://www.cdc.gov/vaccines/pubs/pinkbook/hpv.html Accessed on October 13, 2016</ref>Prognosis of [[Human papillomavirus|HPV]] infection depends primarily on the type of [[Human papillomavirus|HPV]] causing infection.<ref name="pmid25469338">{{cite journal| author=Yang SH, Kong SK, Lee SH, Lim SY, Park CY| title=Human papillomavirus 18 as a poor prognostic factor in stage I-IIA cervical cancer following primary surgical treatment. | journal=Obstet Gynecol Sci | year= 2014 | volume= 57 | issue= 6 | pages= 492-500 | pmid=25469338 | doi=10.5468/ogs.2014.57.6.492 | pmc=4245343 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25469338  }} </ref><ref name="pmid25283642">{{cite journal| author=No JH, Sung MW, Hah JH, Choi SH, Lee MC, Kim HS et al.| title=Prevalence and prognostic value of human papillomavirus genotypes in tonsillar squamous cell carcinoma: a Korean multicenter study. | journal=Cancer | year= 2015 | volume= 121 | issue= 4 | pages= 535-44 | pmid=25283642 | doi=10.1002/cncr.29086 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25283642  }} </ref><ref name="pmid23861037">{{cite journal| author=Lin BM, Wang H, D'Souza G, Zhang Z, Fakhry C, Joseph AW et al.| title=Long-term prognosis and risk factors among patients with HPV-associated oropharyngeal squamous cell carcinoma. | journal=Cancer | year= 2013 | volume= 119 | issue= 19 | pages= 3462-71 | pmid=23861037 | doi=10.1002/cncr.28250 | pmc=3788050 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23861037  }} </ref><ref name="pmid10028109">{{cite journal| author=Beutner KR, Wiley DJ, Douglas JM, Tyring SK, Fife K, Trofatter K et al.| title=Genital warts and their treatment. | journal=Clin Infect Dis | year= 1999 | volume= 28 Suppl 1 | issue=  | pages= S37-56 | pmid=10028109 | doi=10.1086/514722 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10028109  }} </ref><ref name="pmid12952805">{{cite journal| author=Ferenczy A, Coutlée F, Franco E, Hankins C| title=Human papillomavirus and HIV coinfection and the risk of neoplasias of the lower genital tract: a review of recent developments. | journal=CMAJ | year= 2003 | volume= 169 | issue= 5 | pages= 431-4 | pmid=12952805 | doi= | pmc=183297 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12952805  }} </ref>


==Diagnosis==
==Diagnosis==
===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 [[Human papillomavirus|HPV]] are asymptomatic. The clinical manifestation of [[Human papillomavirus|HPV]] infection is [[wart]] that sometimes might be painful.<ref name="pmid2850861">{{cite journal |vauthors=Jablonska S, Orth G, Obalek S, Croissant O |title=Cutaneous warts. Clinical, histologic, and virologic correlations |journal=Clin. Dermatol. |volume=3 |issue=4 |pages=71–82 |year=1985 |pmid=2850861 |doi= |url=}}</ref>
===Laboratory Findings===
===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 [[Georgios Papanikolaou|Papanicolaou]] screening, colloquially known as "[[Pap test|Pap]]" smear testing.
Certain types of sexually transmitted [[Human papillomavirus|HPVs]] can cause [[cervical cancer]]. Persistent infection with one or more of about a dozen of these "high-risk" [[Human papillomavirus|HPV]] types is an important factor in nearly all cases of [[cervical cancer]]. The development of [[Human papillomavirus|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 [[Georgios Papanikolaou|Papanicolaou]] screening, colloquially known as "[[Pap test|Pap]]" smear testing. A cervical [[Pap smear]] with [[Human papillomavirus|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 test|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 [[Human papillomavirus|HPV]]-induced cancer.<ref>{{cite journal |author=Lowy DR, Schiller JT |title=Prophylactic human papillomavirus vaccines |journal=J. Clin. Invest. |volume=116 |issue=5 |pages=1167-73 |year=2006 |pmid=16670757 |doi=10.1172/JCI28607}}</ref>
[[Image:HPV tree 1.png|thumb|center|350px|Notable HPV types and associated diseases]]
<br clear="left"/>
 
==Treatment==
There is no definitive medical treatment of HPV infection. However, treatment is mainly aimed to treat [[warts]] or [[Precancerous|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]].<ref name=CDC>{{Cite journal| issn = 1545-8601| volume = 64| issue = RR-03| pages = 1–137| last1 = Workowski| first1 = Kimberly A.| last2 = Bolan| first2 = Gail A.| title = Sexually transmitted diseases treatment guidelines, 2015| journal = MMWR. Recommendations and reports: Morbidity and mortality weekly report. Recommendations and reports / Centers for Disease Control| date = 2015-06-05| pmid = 26042815}}</ref><ref name="pmid18360317">{{cite journal| author=Gotovtseva EP, Kapadia AS, Smolensky MH, Lairson DR| title=Optimal frequency of imiquimod (aldara) 5% cream for the treatment of external genital warts in immunocompetent adults: a meta-analysis. | journal=Sex Transm Dis | year= 2008 | volume= 35 | issue= 4 | pages= 346-51 | pmid=18360317 | doi=10.1097/OLQ.0b013e31815ea8d1 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18360317  }} </ref><ref name="pmid16820073">{{cite journal| author=Garland SM, Waddell R, Mindel A, Denham IM, McCloskey JC| title=An open-label phase II pilot study investigating the optimal duration of imiquimod 5% cream for the treatment of external genital warts in women. | journal=Int J STD AIDS | year= 2006 | volume= 17 | issue= 7 | pages= 448-52 | pmid=16820073 | doi=10.1258/095646206777689161 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16820073  }} </ref><ref name="pmid9449906">{{cite journal| author=Edwards L, Ferenczy A, Eron L, Baker D, Owens ML, Fox TL et al.| title=Self-administered topical 5% imiquimod cream for external anogenital warts. HPV Study Group. Human PapillomaVirus. | journal=Arch Dermatol | year= 1998 | volume= 134 | issue= 1 | pages= 25-30 | pmid=9449906 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9449906  }} </ref><ref name="pmid18292715">{{cite journal| author=| title=Veregen: a botanical for treatment of genital warts. | journal=Med Lett Drugs Ther | year= 2008 | volume= 50 | issue= 1280 | pages= 15-6 | pmid=18292715 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18292715  }} </ref><ref name="pmid3531860">{{cite journal| author=Eron LJ, Judson F, Tucker S, Prawer S, Mills J, Murphy K et al.| title=Interferon therapy for condylomata acuminata. | journal=N Engl J Med | year= 1986 | volume= 315 | issue= 17 | pages= 1059-64 | pmid=3531860 | doi=10.1056/NEJM198610233151704 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3531860  }} </ref>
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.<ref name=CDC10>{{Cite journal| issn = 1545-8601| volume = 64| issue = RR-03| pages = 1–137| last1 = Workowski| first1 = Kimberly A.| last2 = Bolan| first2 = Gail A.| title = Sexually transmitted diseases treatment guidelines, 2015| journal = MMWR. Recommendations and reports: Morbidity and mortality weekly report. Recommendations and reports / Centers for Disease Control| date = 2015-06-05| pmid = 26042815}}</ref>


==Prevention==
==Prevention==
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.
Most people become infected with various cutaneous [[Human papillomavirus|HPV t]]<nowiki/>ypes during childhood. [[Papillomavirus|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 [[Human papillomavirus|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:
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 [[Human papillomavirus|HPV]]<nowiki/>s:


==References==
==References==


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Latest revision as of 22:13, 29 July 2020

Sexually transmitted diseases Main Page

Human papillomavirus Microchapters

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Pathophysiology

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Diagnosis

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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]

Overview

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]

Classification

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]

Pathophysiology

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.

Screening

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]

Diagnosis

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


Treatment

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]

Prevention

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:

References

  1. ↑ Walboomers JM, Jacobs MV, Manos MM; et al. (1999). "Human papillomavirus is a necessary cause of invasive cervical cancer worldwide". J. Pathol. 189 (1): 12–9. doi:10.1002/(SICI)1096-9896(199909)189:1<12::AID-PATH431>3.0.CO;2-F. PMID 10451482.
  2. ↑ zur Hausen H, de Villiers EM (1994). "Human papillomaviruses". Annu. Rev. Microbiol. 48: 427–47. PMID 7826013.
  3. ↑ "Reference clones at International HPV Reference Center".
  4. ↑ Bernard HU, Burk RD, Chen Z, van Doorslaer K, zur Hausen H, de Villiers EM (2010). "Classification of papillomaviruses (PVs) based on 189 PV types and proposal of taxonomic amendments". Virology. 401 (1): 70–9. doi:10.1016/j.virol.2010.02.002. PMC 3400342. PMID 20206957.
  5. ↑ Jenson AB, Kurman RJ, Lancaster WD (1985). "Detection of papillomavirus common antigens in lesions of skin and mucosa". Clin. Dermatol. 3 (4): 56–63. PMID 2463866.
  6. ↑ Bzhalava D, Eklund C, Dillner J (2015). "International standardization and classification of human papillomavirus types". Virology. 476: 341–4. doi:10.1016/j.virol.2014.12.028. PMID 25577151.
  7. ↑ Hernandez BY, Wilkens LR, Zhu X, Thompson P, McDuffie K, Shvetsov YB; et al. (2008). "Transmission of human papillomavirus in heterosexual couples". Emerg Infect Dis. 14 (6): 888–94. doi:10.3201/eid1406.070616. PMC 2600292. PMID 18507898.
  8. ↑ Doorbar J (2005). "The papillomavirus life cycle". J Clin Virol. 32 Suppl 1: S7–15. doi:10.1016/j.jcv.2004.12.006. PMID 15753007.
  9. ↑ Doorbar J, Quint W, Banks L, Bravo IG, Stoler M, Broker TR; et al. (2012). "The biology and life-cycle of human papillomaviruses". Vaccine. 30 Suppl 5: F55–70. doi:10.1016/j.vaccine.2012.06.083. PMID 23199966.
  10. ↑ Moody CA, Laimins LA (2010). "Human papillomavirus oncoproteins: pathways to transformation". Nat Rev Cancer. 10 (8): 550–60. doi:10.1038/nrc2886. PMID 20592731.
  11. ↑ Masuda H, Miller C, Koeffler HP, Battifora H, Cline MJ (1987). "Rearrangement of the p53 gene in human osteogenic sarcomas". Proc Natl Acad Sci U S A. 84 (21): 7716–9. PMC 299371. PMID 2823272.
  12. ↑ Tommasino M, Adamczewski JP, Carlotti F, Barth CF, Manetti R, Contorni M; et al. (1993). "HPV16 E7 protein associates with the protein kinase p33CDK2 and cyclin A." Oncogene. 8 (1): 195–202. PMID 8380917.
  13. ↑ Baseman JG, Koutsky LA (2005). "The epidemiology of human papillomavirus infections". J. Clin. Virol. 32 Suppl 1: S16–24. doi:10.1016/j.jcv.2004.12.008. PMID 15753008. *Note: The authors state on page S17 "Overall, these DNA-based studies, combined with measurements of type-specific antibodies against HPV capsid antigens, have shown that most (>50%) sexually active women have been infected by one or more genital HPV types at some point in time."
  14. ↑ 14.0 14.1 http://www.cdc.gov/vaccines/pubs/pinkbook/hpv.html#epi Accessed on October 13, 2016
  15. ↑ Moyer VA, U.S. Preventive Services Task Force (2012). "Screening for cervical cancer: U.S. Preventive Services Task Force recommendation statement". Ann Intern Med. 156 (12): 880–91, W312. doi:10.7326/0003-4819-156-12-201206190-00424. PMID 22711081.
  16. ↑ McGraw SL, Ferrante JM (2014). "Update on prevention and screening of cervical cancer". World J Clin Oncol. 5 (4): 744–52. doi:10.5306/wjco.v5.i4.744. PMC 4129537. PMID 25302174.
  17. ↑ Ault KA (2006). "Epidemiology and natural history of human papillomavirus infections in the female genital tract". Infect Dis Obstet Gynecol. 2006 Suppl: 40470. doi:10.1155/IDOG/2006/40470. PMC 1581465. PMID 16967912.
  18. ↑ Castle PE, Schiffman M, Herrero R, Hildesheim A, Rodriguez AC, Bratti MC; et al. (2005). "A prospective study of age trends in cervical human papillomavirus acquisition and persistence in Guanacaste, Costa Rica". J Infect Dis. 191 (11): 1808–16. doi:10.1086/428779. PMID 15871112.
  19. ↑ Woodman CB, Collins S, Winter H, Bailey A, Ellis J, Prior P; et al. (2001). "Natural history of cervical human papillomavirus infection in young women: a longitudinal cohort study". Lancet. 357 (9271): 1831–6. doi:10.1016/S0140-6736(00)04956-4. PMID 11410191.
  20. ↑ Ho GY, Bierman R, Beardsley L, Chang CJ, Burk RD (1998). "Natural history of cervicovaginal papillomavirus infection in young women". N Engl J Med. 338 (7): 423–8. doi:10.1056/NEJM199802123380703. PMID 9459645.
  21. ↑ Yang SH, Kong SK, Lee SH, Lim SY, Park CY (2014). "Human papillomavirus 18 as a poor prognostic factor in stage I-IIA cervical cancer following primary surgical treatment". Obstet Gynecol Sci. 57 (6): 492–500. doi:10.5468/ogs.2014.57.6.492. PMC 4245343. PMID 25469338.
  22. ↑ No JH, Sung MW, Hah JH, Choi SH, Lee MC, Kim HS; et al. (2015). "Prevalence and prognostic value of human papillomavirus genotypes in tonsillar squamous cell carcinoma: a Korean multicenter study". Cancer. 121 (4): 535–44. doi:10.1002/cncr.29086. PMID 25283642.
  23. ↑ Lin BM, Wang H, D'Souza G, Zhang Z, Fakhry C, Joseph AW; et al. (2013). "Long-term prognosis and risk factors among patients with HPV-associated oropharyngeal squamous cell carcinoma". Cancer. 119 (19): 3462–71. doi:10.1002/cncr.28250. PMC 3788050. PMID 23861037.
  24. ↑ Beutner KR, Wiley DJ, Douglas JM, Tyring SK, Fife K, Trofatter K; et al. (1999). "Genital warts and their treatment". Clin Infect Dis. 28 Suppl 1: S37–56. doi:10.1086/514722. PMID 10028109.
  25. ↑ Ferenczy A, Coutlée F, Franco E, Hankins C (2003). "Human papillomavirus and HIV coinfection and the risk of neoplasias of the lower genital tract: a review of recent developments". CMAJ. 169 (5): 431–4. PMC 183297. PMID 12952805.
  26. ↑ Jablonska S, Orth G, Obalek S, Croissant O (1985). "Cutaneous warts. Clinical, histologic, and virologic correlations". Clin. Dermatol. 3 (4): 71–82. PMID 2850861.
  27. ↑ Lowy DR, Schiller JT (2006). "Prophylactic human papillomavirus vaccines". J. Clin. Invest. 116 (5): 1167–73. doi:10.1172/JCI28607. PMID 16670757.
  28. ↑ Workowski, Kimberly A.; Bolan, Gail A. (2015-06-05). "Sexually transmitted diseases treatment guidelines, 2015". MMWR. Recommendations and reports: Morbidity and mortality weekly report. Recommendations and reports / Centers for Disease Control. 64 (RR-03): 1–137. ISSN 1545-8601. PMID 26042815.
  29. ↑ Gotovtseva EP, Kapadia AS, Smolensky MH, Lairson DR (2008). "Optimal frequency of imiquimod (aldara) 5% cream for the treatment of external genital warts in immunocompetent adults: a meta-analysis". Sex Transm Dis. 35 (4): 346–51. doi:10.1097/OLQ.0b013e31815ea8d1. PMID 18360317.
  30. ↑ Garland SM, Waddell R, Mindel A, Denham IM, McCloskey JC (2006). "An open-label phase II pilot study investigating the optimal duration of imiquimod 5% cream for the treatment of external genital warts in women". Int J STD AIDS. 17 (7): 448–52. doi:10.1258/095646206777689161. PMID 16820073.
  31. ↑ Edwards L, Ferenczy A, Eron L, Baker D, Owens ML, Fox TL; et al. (1998). "Self-administered topical 5% imiquimod cream for external anogenital warts. HPV Study Group. Human PapillomaVirus". Arch Dermatol. 134 (1): 25–30. PMID 9449906.
  32. ↑ "Veregen: a botanical for treatment of genital warts". Med Lett Drugs Ther. 50 (1280): 15–6. 2008. PMID 18292715.
  33. ↑ Eron LJ, Judson F, Tucker S, Prawer S, Mills J, Murphy K; et al. (1986). "Interferon therapy for condylomata acuminata". N Engl J Med. 315 (17): 1059–64. doi:10.1056/NEJM198610233151704. PMID 3531860.
  34. ↑ Workowski, Kimberly A.; Bolan, Gail A. (2015-06-05). "Sexually transmitted diseases treatment guidelines, 2015". MMWR. Recommendations and reports: Morbidity and mortality weekly report. Recommendations and reports / Centers for Disease Control. 64 (RR-03): 1–137. ISSN 1545-8601. PMID 26042815.

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