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{{Human papillomavirus}}
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==Overview==
==Overview==
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.
Various oncogenic types of HPV can be detected for cancer screening purposes. 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.


==Laboratory Findings==
==Laboratory Findings==
HPV infection can be detected and managed in various ways. HPV tests are available to detect oncogenic types of HPV infection and are used in the context of [[cervical cancer]] screening and management or follow-up of abnormal cervical cytology or histology.<ref name="pmid21282563">{{cite journal |vauthors=Schiffman M, Wentzensen N, Wacholder S, Kinney W, Gage JC, Castle PE |title=Human papillomavirus testing in the prevention of cervical cancer |journal=J. Natl. Cancer Inst. |volume=103 |issue=5 |pages=368–83 |year=2011 |pmid=21282563 |pmc=3046952 |doi=10.1093/jnci/djq562 |url=}}</ref><ref name="urlWHO | WHO HPV LabNet">{{cite web |url=http://www.who.int/biologicals/areas/human_papillomavirus/WHO_HPV_LabNet/en/ |title=WHO &#124; WHO HPV LabNet |format= |work= |accessdate=}}</ref>
Currently, 3 main methods to detect HPV are available:<ref name="pmid22913405">{{cite journal |vauthors=Chan PK, Picconi MA, Cheung TH, Giovannelli L, Park JS |title=Laboratory and clinical aspects of human papillomavirus testing |journal=Crit Rev Clin Lab Sci |volume=49 |issue=4 |pages=117–36 |year=2012 |pmid=22913405 |pmc=3469219 |doi=10.3109/10408363.2012.707174 |url=}}</ref>
*HPV DNA testing
*HPV RNA testing
*Cellular markers screening
===DNA based assays===
They can be divided into:
*Target amplification methods ([[Polymerase chain reaction|PCR]] with consensus or type-specific primers)
*Signal amplification methods (liquid-phase or [[Fluorescence in situ hybridization|in situ hybridization]]): Hybrid capture HPV DNA assay is the prototype in this method and can detect 13 different types of high risk HPVs.<ref name="pmid22913405">{{cite journal |vauthors=Chan PK, Picconi MA, Cheung TH, Giovannelli L, Park JS |title=Laboratory and clinical aspects of human papillomavirus testing |journal=Crit Rev Clin Lab Sci |volume=49 |issue=4 |pages=117–36 |year=2012 |pmid=22913405 |pmc=3469219 |doi=10.3109/10408363.2012.707174 |url=}}</ref>
===RNA based assays===
These tests look for expression of E6 and/or E7 RNA in HPV genome and provide higher sensitivity and specificity than DNA based testings. Persistent expression of E6 and E7 could serve as an indicator of progression from intraepithelial neoplasia to invasive cancer.<ref name="pmid9600817">{{cite journal |vauthors=Sotlar K, Selinka HC, Menton M, Kandolf R, Bültmann B |title=Detection of human papillomavirus type 16 E6/E7 oncogene transcripts in dysplastic and nondysplastic cervical scrapes by nested RT-PCR |journal=Gynecol. Oncol. |volume=69 |issue=2 |pages=114–21 |year=1998 |pmid=9600817 |doi=10.1006/gyno.1998.4994 |url=}}</ref><ref name="pmid15943992">{{cite journal |vauthors=Lie AK, Risberg B, Borge B, Sandstad B, Delabie J, Rimala R, Onsrud M, Thoresen S |title=DNA- versus RNA-based methods for human papillomavirus detection in cervical neoplasia |journal=Gynecol. Oncol. |volume=97 |issue=3 |pages=908–15 |year=2005 |pmid=15943992 |doi=10.1016/j.ygyno.2005.02.026 |url=}}</ref><ref name="pmid22913405">{{cite journal |vauthors=Chan PK, Picconi MA, Cheung TH, Giovannelli L, Park JS |title=Laboratory and clinical aspects of human papillomavirus testing |journal=Crit Rev Clin Lab Sci |volume=49 |issue=4 |pages=117–36 |year=2012 |pmid=22913405 |pmc=3469219 |doi=10.3109/10408363.2012.707174 |url=}}</ref>
===Cellular markers screening===
They are not FDA approved currently, but studies demonstrated high sensitivity to detect cervical dysplasia.<ref name="pmid24096620">{{cite journal |vauthors=Ikenberg H, Bergeron C, Schmidt D, Griesser H, Alameda F, Angeloni C, Bogers J, Dachez R, Denton K, Hariri J, Keller T, von Knebel Doeberitz M, Neumann HH, Puig-Tintore LM, Sideri M, Rehm S, Ridder R |title=Screening for cervical cancer precursors with p16/Ki-67 dual-stained cytology: results of the PALMS study |journal=J. Natl. Cancer Inst. |volume=105 |issue=20 |pages=1550–7 |year=2013 |pmid=24096620 |pmc=3814411 |doi=10.1093/jnci/djt235 |url=}}</ref>


===Pap Smear===
{{main|Pap smear}}
[[Image:ThinPrep Pap smear HPV.jpeg|thumb|left|350px|ThinPrep Pap smear with group of normal cervical cells on left and HPV-infected cells on right. The HPV-infected cells show features typical of [[Koilocyte|koilocytes]]: enlarged (x2 or x3) nuclei and hyperchromasia.]]


The Pap test is an effective strategy for reducing the risk of invasive cervical cancer. The Pap test involves taking cells from the cervix and putting them on a small glass slide and examining them under a microscope to look for abnormal cells. This method is 70% to 80% effective in detecting HPV-caused cellular abnormalities. A more sensitive method is a “Thin Prep,” in which the cells from the cervix are placed in a liquid solution. This test is 85% to 95% effective in detecting HPV-caused cellular abnormalities. The last Pap test method is mainly used on women over 30. It is a combination Pap-HPV DNA test. If this test comes back negative women can usually wait 3 years before having the test done again. Detailed inspection of the cervix by [[colposcopy]] may be indicated if ''abnormal cells'' are detected by routine Pap smear. A frequently occurring example of an ''abnormal cell'' found in association with HPV is the [[koilocyte]]. (See figure.)
==Pap Smear==
 
The Pap test is an effective strategy for reducing the risk of invasive cervical cancer. The Pap test involves taking cells from the cervix and putting them on a small glass slide and examining them under a microscope to look for abnormal cells. This method is 70% to 80% effective in detecting HPV-caused cellular abnormalities. A more sensitive method is a “Thin Prep,” in which the cells from the cervix are placed in a liquid solution. This test is 85% to 95% effective in detecting HPV-caused cellular abnormalities. The last Pap test method is mainly used on women over 30. It is a combination Pap-HPV DNA test. If this test comes back negative women can usually wait 3 years before having the test done again. Detailed inspection of the cervix by [[colposcopy]] may be indicated if ''abnormal cells'' are detected by routine Pap smear. A frequently occurring example of an ''abnormal cell'' found in association with HPV is the [[koilocyte]].<ref name="pmid26496321">{{cite journal |vauthors=Sopracordevole F, Mancioli F, Clemente N, De Piero G, Buttignol M, Giorda G, Ciavattini A |title=Abnormal Pap Smear and Diagnosis of High-Grade Vaginal Intraepithelial Neoplasia: A Retrospective Cohort Study |journal=Medicine (Baltimore) |volume=94 |issue=42 |pages=e1827 |year=2015 |pmid=26496321 |pmc=4620759 |doi=10.1097/MD.0000000000001827 |url=}}</ref>(See figure.)
The [[Center for Disease Control]] (CDC) recommends that women get a Pap test no later than 3 years after their first sexual encounter and no later than 21 years of age. Women should have a Pap test every year until age 30. After age 30, women should discuss risk factors with their health care provider to determine whether a Pap test should be done yearly. If risk factors are low and previous Pap tests have been negative, most women only need to have tests every 2-3 years until 65 years of age (Centers for Disease Control 2005). Since these screening tools have been developed there has been a 70% decrease in cervical cancer deaths over the last 50 years. Pap smear testing has proven to be one of the most successful screening tests in the history of medicine, but the [[American College of Obstetricians and Gynecologists]] states the even the newer liquid based cytology methods (Thinprep and Surepath) may miss 15-35% of CIN3's and cancer.
<gallery>
 
Image:ThinPrep Pap smear HPV.jpeg|ThinPrep Pap smear with group of normal cervical cells on left and HPV-infected cells on right. The HPV-infected cells show features typical of [[Koilocyte|koilocytes]]: enlarged (x2 or x3) nuclei and hyperchromasia.
A study published in April 2007 suggested the act of performing a Pap smear produces an inflammatory [[cytokine]] response, which may initiate immunologic clearance of HPV, therefore reducing the risk of cervical cancer. Women who had even a single Pap smear in their history had a lower incidence of cancer. "A statistically significant decline in the HPV positivity rate correlated with the lifetime number of Pap smears received."<ref>[http://www.oncolink.com/resources/article.cfm?c=3&s=8&ss=23&Year=2007&Month=5&id=14201], J Inflamm 2007;4.</ref>
</gallery>
 
It has been suggested that Pap smear screening for anal cancer might be of benefit for some sub-populations of gay men.<ref>{{cite journal |author=Chin-Hong PV, Vittinghoff E, Cranston RD, ''et al'' |title=Age-related prevalence of anal cancer precursors in homosexual men: the EXPLORE study |journal=J. Natl. Cancer Inst. |volume=97 |issue=12 |pages=896-905 |year=2005 |pmid=15956651 |doi=10.1093/jnci/dji163}}</ref>
 
===HPV Testing===
 
An HPV test detects certain types of human papillomavirus (HPVs), depending on the test. A method for detecting the [[DNA]] of high-risk HPVs has recently been added to the range of clinical options for cervical cancer screening. In March 2003, the US [[Food and Drug Administration|FDA]] approved a "hybrid-capture" test, marketed by Digene, as a primary screening tool for detecting high-risk HPV infections that may lead to cervical cancer. This test was also approved for use as an adjunct to Pap testing, and may be ordered in response to abnormal Pap smear results.
 
Adding the HPV test for all women over thirty improves the sensitivity of the cytology test alone to nearly 100% and gives the clinician the option to extend the pap smear screening interval out to three years. 
 
According to the CDC there is currently no test commercially available to determine infection in men. Genital warts are the only visible sign of HPV in men, and can be identified with a visual check of the genital area. These visible growths, however, are usually the result of non-carcinogenic HPV types. Vinegar solutions have been used to identify flat warts by making them more distinct, but most providers have found this technique helpful only in moist areas, such as the female genital tract.<ref>http://www.cdc.gov/STD/HPV/STDFact-HPV-and-men.htm#test [January 2007]</ref>


==References==
==References==


{{Reflist|2}}
{{Reflist|2}}
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Latest revision as of 22:13, 29 July 2020

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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]

Overview

Various oncogenic types of HPV can be detected for cancer screening purposes. 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.

Laboratory Findings

HPV infection can be detected and managed in various ways. HPV tests are available to detect oncogenic types of HPV infection and are used in the context of cervical cancer screening and management or follow-up of abnormal cervical cytology or histology.[1][2] Currently, 3 main methods to detect HPV are available:[3]

  • HPV DNA testing
  • HPV RNA testing
  • Cellular markers screening

DNA based assays

They can be divided into:

  • Target amplification methods (PCR with consensus or type-specific primers)
  • Signal amplification methods (liquid-phase or in situ hybridization): Hybrid capture HPV DNA assay is the prototype in this method and can detect 13 different types of high risk HPVs.[3]

RNA based assays

These tests look for expression of E6 and/or E7 RNA in HPV genome and provide higher sensitivity and specificity than DNA based testings. Persistent expression of E6 and E7 could serve as an indicator of progression from intraepithelial neoplasia to invasive cancer.[4][5][3]

Cellular markers screening

They are not FDA approved currently, but studies demonstrated high sensitivity to detect cervical dysplasia.[6]


Pap Smear

The Pap test is an effective strategy for reducing the risk of invasive cervical cancer. The Pap test involves taking cells from the cervix and putting them on a small glass slide and examining them under a microscope to look for abnormal cells. This method is 70% to 80% effective in detecting HPV-caused cellular abnormalities. A more sensitive method is a “Thin Prep,” in which the cells from the cervix are placed in a liquid solution. This test is 85% to 95% effective in detecting HPV-caused cellular abnormalities. The last Pap test method is mainly used on women over 30. It is a combination Pap-HPV DNA test. If this test comes back negative women can usually wait 3 years before having the test done again. Detailed inspection of the cervix by colposcopy may be indicated if abnormal cells are detected by routine Pap smear. A frequently occurring example of an abnormal cell found in association with HPV is the koilocyte.[7](See figure.)

References

  1. Schiffman M, Wentzensen N, Wacholder S, Kinney W, Gage JC, Castle PE (2011). "Human papillomavirus testing in the prevention of cervical cancer". J. Natl. Cancer Inst. 103 (5): 368–83. doi:10.1093/jnci/djq562. PMC 3046952. PMID 21282563.
  2. "WHO | WHO HPV LabNet".
  3. 3.0 3.1 3.2 Chan PK, Picconi MA, Cheung TH, Giovannelli L, Park JS (2012). "Laboratory and clinical aspects of human papillomavirus testing". Crit Rev Clin Lab Sci. 49 (4): 117–36. doi:10.3109/10408363.2012.707174. PMC 3469219. PMID 22913405.
  4. Sotlar K, Selinka HC, Menton M, Kandolf R, Bültmann B (1998). "Detection of human papillomavirus type 16 E6/E7 oncogene transcripts in dysplastic and nondysplastic cervical scrapes by nested RT-PCR". Gynecol. Oncol. 69 (2): 114–21. doi:10.1006/gyno.1998.4994. PMID 9600817.
  5. Lie AK, Risberg B, Borge B, Sandstad B, Delabie J, Rimala R, Onsrud M, Thoresen S (2005). "DNA- versus RNA-based methods for human papillomavirus detection in cervical neoplasia". Gynecol. Oncol. 97 (3): 908–15. doi:10.1016/j.ygyno.2005.02.026. PMID 15943992.
  6. Ikenberg H, Bergeron C, Schmidt D, Griesser H, Alameda F, Angeloni C, Bogers J, Dachez R, Denton K, Hariri J, Keller T, von Knebel Doeberitz M, Neumann HH, Puig-Tintore LM, Sideri M, Rehm S, Ridder R (2013). "Screening for cervical cancer precursors with p16/Ki-67 dual-stained cytology: results of the PALMS study". J. Natl. Cancer Inst. 105 (20): 1550–7. doi:10.1093/jnci/djt235. PMC 3814411. PMID 24096620.
  7. Sopracordevole F, Mancioli F, Clemente N, De Piero G, Buttignol M, Giorda G, Ciavattini A (2015). "Abnormal Pap Smear and Diagnosis of High-Grade Vaginal Intraepithelial Neoplasia: A Retrospective Cohort Study". Medicine (Baltimore). 94 (42): e1827. doi:10.1097/MD.0000000000001827. PMC 4620759. PMID 26496321.

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