Human papillomavirus
From Ganfyd
Web Resources for Human papillomavirus
[1]] B07]] ICD-10 page] ICD-10 search
ICD 10 code: B07]]
Relevant Clinical Literature
UK Guidance
Other Wikis
Medpedia on Human papillomavirus (Less technical, good quality control)
Wikipedia on Human papillomavirus (Less technical, ? quality control)
Also known as human papilloma virus or by the abbreviation HPV. It is a double-stranded DNA virus, of which there are over 100 strains, categorised by genotype, not serotype.
Contents |
Clinical
Warts
The most common manifestation is viral warts. These are usually on the skin, presenting as verrucae, but other sites include the larynx and anogenital area.
Over 90% of genital warts are caused by HPV genotypes 6 and 11.
Cancers
Most cervical cancer (70% world-wide) is caused by HPV genotypes 16 and 18. These genotypes also cause a similar proportion of anal carcinomas, and some penile cancers. An increasing proportion of oropharyngeal squamous cell carcinomas are linked to HPV 16[2] which improves the prognosis[3]. Perhaps the viral proteins E6 and E7 make HPV-positive tumours more immunogenic but HPV-negative tumours also have other molecular differences like frequent p53 mutations.
Investigations
Cytological/Histological Tests
Exfoliative cytological of the cervix in the form of the PAP test test does not detect HPV per se, but rather detects cytopathological changes that are characteristic of HPV, e.g. koilocytosis. In addition, the presence of dysplasia, most of which is caused by HPV, is a surrogate measure of viral activity.
Similar changes can be seen on histological biopsies.
HPV DNA Testing
In the context of cervical HPV, much more emotive to be told you have sexual transmitted disease!
The method of detection depends on the material available and the main aim of testing.
DNA testing HPV DNA can be detected on histological specimens using in situ hybridisation.
PCR methods are extremely sensitive and can detect relatively low copy numbers of viral genome, including viral genome integrated into host cells. HPV infections can persist in that some cells in 'healed' warts contain integrated viral genome. PCR methods can therefore be too sensitive as it would potentially detect quiescent infection which may not be clinically significant.
In the UK, the HPV testing in cervical cytology relies on a hybrid capture assay. This shares some principles of ELISA, but the initial step depends on hydrization of viral DNA to HPV-specific RNA probes. This DNA-RNA hybrid is then 'captured' by antibodies that target the molecular shape of RNA-DNA bindings. Secondary antibodies labelled with fluorescent/chemiluminescent probes can then be used to colorimetrically quantify the viral DNA.
Blood tests
Serology can show previous exposure, but as the virus is sometimes shielded from the immune system, negative serology does not exclude infecion.
Treatment
Smoking cessation can promote HPV-induced cytopathology[4] so this makes sense to encourage in precancerous lesions.
Medical
- Topical immunotherapy - Imiquimod, resiquimod with warts.
Cervical cancer
For treatment of HPV-induced cervical cancer see cervical cancer.
Prevention
Safe sex
In principle, adopting scrupulous safe sexual practices will reduce the risk of contracting HPV sexually.
In practice, the evidence does not show a strong protective effect from barrier methods.[5] Several explanations are possible:[6] One limitation of most studies of this sort is the reliance on self-reported questionnaires where complete adherence cannot be guaranteed. The way condoms are used may also influence the efficacy. Condoms used primarily as a contraceptive may allow significant skin to skin contact that would be reduced if condoms were used more scrupulously for STI prophylaxis. As a final point, most people are infected with HPV within a few years of their sexual debut. Risk of infection is fairly high, even in young women who have had just 1 male sex partner.[7]
Non-genital warts
Vaccination
Two vaccines are currently licensed and available in the UK and Europe:
- Gardasil™, from Sanofi Pasteur MSD, which was licensed in Europe on 21 September 2006; and
- Cervarix™, from GlaxoSmithKline, which was licensed in the UK and Europe in September 2007 (but which is not licensed in USA).[8]
See Human papillomavirus vaccine (content previously on this page has been moved there) or Wikipedia HPV vaccine page for more details.
Post exposure prophylaxis
Not available
Notification
Not formally notifiable (although this may change if a vaccine is introduced into the national schedules).
The virus
Genome
Codes for 8 genes of which E6 and E7 are the primary oncoproteins.
Oncological potential
- In simple terms:
- E6 blocks p53 and thus apoptosis
- E7 blocks retinoblastoma tumour suppression protein (pRB) which abolishes the cell cycle arrest[9]
- However matters are much more complex than this as at latest count E6/E7 down-regulates 360 human genes and upregulates 288 genes many of which are involved in tumor-relevant processes, such as apoptosis control, cell cycle regulation, spindle formation or RNA processing and splicing.[10]. Retinoblastoma-binding protein 4 has been recently postulated as the primary oncological event for E7 binding[11].
The UK cervical screening programme will stratify followup of abnormal cervical cytology after treatment according to whether HPV has been eradicated.
This article is a work in progress. Please feel free to contribute to it.
External links
- Department of Health information on HPV, including:
- Statement on HPV vaccine from Joint Committee on Vaccination and Immunisation[12]
- Information Centre on HPV and Cervical Cancer from WHO & ICO (Institut Català d'Oncologia)
- US CDC/NIH factsheet on HPV
- US CDC Genital HPV Infection Fact Sheet
- BBC article on HPV
- Wikipedia article on HPV
- Article on cervical cancer from Cancer Research UK
- Information on genital warts form the UK Health Protection Agency
- Information from Sanofi Pasteur MSD website about "Gardasil™", an as-yet-unlicensed vaccine against HPV types 6, 11, 16, and 18, dated 8/4/05
- Information from GlaxoSmithKline website about "Cervarix™", an as-yet-unlicensed vaccine against HPV types 16 and 18, dated 6/4/06
- Gardasil Watch - which claims to be "Your absolutely and completely INDEPENDENT source of reviews and news about Gardasil, an upcoming vaccine for cervical cancer"
- British Journal of Cancer, which published a recent article on HPV vaccination.[13]
- Cost-effectiveness modelling paper.[14]
- US ACIP recommendations.[15]
- Canadian recommendations.[16]
- Australian recommendations[17]
- Link to German Ständigen Impfkommission (STIKO) recommendations.
References
- ↑ Smith JS, Lindsay L, Hoots B, Keys J, Franceschi S, Winer R, Clifford GM. Human papillomavirus type distribution in invasive cervical cancer and high-grade cervical lesions: a meta-analysis update. International journal of cancer. Journal international du cancer. 2007 Aug 1; 121(3):621-32.(Link to article – subscription may be required.)
- ↑ Näsman A, Attner P, Hammarstedt L, Du J, Eriksson M, Giraud G, Ahrlund-Richter S, Marklund L, Romanitan M, Lindquist D, Ramqvist T, Lindholm J, Sparén P, Ye W, Dahlstrand H, Munck-Wikland E, Dalianis T. Incidence of human papillomavirus (HPV) positive tonsillar carcinoma in Stockholm, Sweden: an epidemic of viral-induced carcinoma? International journal of cancer. Journal international du cancer. 2009 Jul 15; 125(2):362-6.(Link to article – subscription may be required.)
- ↑ Dahlstrand H, Näsman A, Romanitan M, Lindquist D, Ramqvist T, Dalianis T. Human papillomavirus accounts both for increased incidence and better prognosis in tonsillar cancer. Anticancer research. 2008 Mar-Apr; 28(2B):1133-8.
- ↑ Szarewski A, Jarvis MJ, Sasieni P, Anderson M, Edwards R, Steele SJ, Guillebaud J, Cuzick J. Effect of smoking cessation on cervical lesion size. Lancet. 1996 Apr 6; 347(9006):941-3.
- ↑ Manhart LE, Koutsky LA. Do condoms prevent genital HPV infection, external genital warts, or cervical neoplasia? A meta-analysis. Sexually transmitted diseases. 2002 Nov; 29(11):725-35.
- ↑ Epstein RJ. Primary prevention of human papillomavirus-dependent neoplasia: no condom, no sex. European journal of cancer (Oxford, England : 1990). 2005 Nov; 41(17):2595-600.(Link to article – subscription may be required.)
- ↑ Winer RL, Feng Q, Hughes JP, O'Reilly S, Kiviat NB, Koutsky LA. Risk of female human papillomavirus acquisition associated with first male sex partner. The Journal of infectious diseases. 2008 Jan 15; 197(2):279-82.(Link to article – subscription may be required.)
- ↑ GSK Press release, September 24, 2007
- ↑ Boulet G, Horvath C, Broeck DV, Sahebali S, Bogers J. Human papillomavirus: E6 and E7 oncogenes. 2007 Jul 19.(Epub ahead of print) (Link to article – subscription may be required.)
- ↑ Kuner R, Vogt M, Sultmann H, Buness A, Dymalla S, Bulkescher J, Fellmann M, Butz K, Poustka A, Hoppe-Seyler F. Identification of cellular targets for the human papillomavirus E6 and E7 oncogenes by RNA interference and transcriptome analyses. . 2007 Jun 23.(Epub ahead of print) (Link to article – subscription may be required.)
- ↑ Kong L, Yu XP, Bai XH, Zhang WF, Zhang Y, Zhao WM, Jia JH, Tang W, Zhou YB, Liu CJ. RbAp48 Is a Critical Mediator Controlling the Transforming Activity of Human Papillomavirus Type 16 in Cervical Cancer. The Journal of biological chemistry. 2007 Sep 7; 282(36):26381-91.(Link to article – subscription may be required.)
- ↑ Joint Committee on Vaccination and Immunisation (JCVI). Human papillomavirus vaccines to protect against cervical cancer. London: Joint Committee on Vaccination and Immunisation, 2008
- ↑ French KM, Barnabas RV, Lehtinen M, Kontula O, Pukkala E, Dillner J, et al. Strategies for the introduction of human papillomavirus vaccination: modelling the optimum age- and sex-specific pattern of vaccination in Finland. Br J Cancer 2007;96(3):514-8. Epub 2007 Jan 23.
- ↑ Elbasha EH, Dasbach EJ, Insinga RP. Model for assessing human papillomavirus vaccination strategies. Emerg Infect Dis (serial on the Internet) 2007;13(1):28-41.
- ↑ Markowitz LE, Dunne EF, Saraiya M, Lawson HW, Chesson H, Unger ER, et al. Quadrivalent Human Papillomavirus vaccine: Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR 2007;56(Early Release):1-26.
- ↑ National Advisory Committee on Immunization (NACI). Statement on humanpapillomavirus vaccine. CCDR 2007;33(ACS-2):1-32.
- ↑ Australian Government Department of Health and Ageing. Australian Government Funding Of Gardasil®: Fact sheet about the Human Papilloma Virus (HPV) vaccines: Australian Government Department of Health and Ageing, 2006.
