Pap test
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2008-07-09T12:09:31Z
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{{ redirect|Pap smear|the similarly named guitar player and actor|Pat Smear}}
[[Image:Cervical AIS, ThinPrep.jpg|right|thumb|[[Cytology|Cytological]] specimen (ThinPrep) from a patient who was later diagnosed with [[cervical cancer|cervical adenocarcinoma in situ]]. There is at least one [[mitosis]].]]
In [[gynecology]], the '''Papanicolaou test''' (also called '''Pap smear''', '''Pap test''', '''cervical smear''', or '''smear test''') is a medical [[screening]] method, invented independently by [[Aurel Babeş]]<ref>O'Dowd MJ, Philipp EE. The History of Obstetrics & Gynaecology. London: Parthenon Publishing Group; 1994: 547</ref> and [[Georgios Papanikolaou]], primarily designed to detect premalignant and malignant processes in the [[ectocervix]]. It may also detect infections and abnormalities in the endocervix and endometrium.
The endocervix may be partially sampled with the device used to obtain the ectocervical sample, but due to the anatomy of this area, consistent and reliable sampling cannot be guaranteed. As abnormal endocervical cells may be sampled, those examining them are taught to recognize them.
The endometrium is not directly sampled with the device used to sample the ectocervix. Cells may exfoliate onto the cervix and be collected from there, so as with endocervical cells, abnormal cells can be recognised if present but the Pap Test should not be used as a screening tool for endometrial malignancy.
The potentially pre-cancerous changes (called [[dysplasia]]s or cervical or endocervical intraepithelial neoplasia) are usually caused by sexually transmitted [[human papillomavirus]]es (HPVs). The test aims to detect and prevent the progression of HPV-induced [[cervical cancer]] and other abnormalities in the female [[genital]] tract by sampling [[cell (biology)|cells]] from the outer opening of the [[cervix]] (Latin for "neck") of the [[uterus]] and the endocervix. The sampling technique changed very little since its invention by [[Georgios Papanikolaou]] (1883–1962) to detect cyclic hormonal changes in vaginal cells in the early 20th century until the development of liquid based cell thinlayer technology. The test remains an effective, widely used method for early detection of cervical cancer and pre-cancer.
The UK's call and recall system is among the best;{{Fact|date=February 2008}} estimates of its effectiveness vary widely but it may prevent about 700 deaths per year in the UK.
It is not a perfect test. "A nurse performing 200 tests each year would prevent a death once in 38 years. During this time she or he would care for over 152 women with abnormal results, over 79 women would be referred for investigation, over 53 would have abnormal biopsy results, and over 17 would have persisting abnormalities for more than two years. At least one woman during the 38 years would die from cervical cancer despite being screened."<ref name="pmid12714468">{{cite journal |author=Raffle AE, Alden B, Quinn M, Babb PJ, Brett MT |title=Outcomes of screening to prevent cancer: analysis of cumulative incidence of cervical abnormality and modelling of cases and deaths prevented |journal=BMJ |volume=326 |issue=7395 |pages=901 |year=2003 |pmid=12714468 |doi=10.1136/bmj.326.7395.901}}</ref>
[[HPV vaccine]] may offer better prospects in the long term.
It is generally recommended that females who have had sex seek regular Pap smear testing. Guidelines on frequency vary, from annually to every five years. If results are abnormal, and depending on the nature of the abnormality, the test may need to be repeated in three to twelve months. If the abnormality requires closer scrutiny, the patient may be referred for detailed inspection of the cervix by [[colposcopy]]. The patient may also be referred for [[HPV test|HPV DNA testing]], which can serve as an adjunct to Pap testing.
About 5% to 7% of pap smears produce abnormal results,{{Fact|date=February 2008}} such as [[dysplasia]], possibly indicating a pre-cancerous condition. Although many low grade cervical dysplasias spontaneously regress without ever leading to [[cervical cancer]], dysplasia can serve as an indication that increased vigilance is needed. Endocervical and endometrial abnormalities can also be detected, as can a number of infectious processes, including yeast and Trichomonas vaginalis. A small proportion of abnormalities are reported as of "uncertain significance".
==Technical aspects==
Samples are collected from the outer opening or '''os''' of the cervix using an [[Aylesbury spatula]] and an endocervical brush, or (more frequently with the advent of [[liquid-based cytology]]) a plastic-fronded broom. The broom is not as good a collection device, since it is much less effective at collecting endocervical material as the spatula and brush.<ref>
{{cite journal |author=Martin-Hirsch P, Lilford R, Jarvis G, Kitchener HC.
|title=Efficacy of cervical-smear collection devices: a systematic review and meta-analysis
|journal=Lancet
|volume=354
|issue=9192
|pages=1763–1770
|year=1999
|pmid=10577637
|doi=10.1016/S0140-6736(99)02353-3}}</ref> The cells are placed on a glass slide and checked for abnormalities in the [[laboratory]].
The sample is stained using the Papanicolaou technique, in which [[tinctorial]] dyes and acids are selectively retained by cells. Unstained cells cannot be visualized with light microscopy. The stains chosen by Papanicolau were selected to highlight cytoplasmic keratinization, which actually has almost nothing to do with the nuclear features used to make diagnoses now.
The sample is then screened by a specially trained and qualified cytotechnologist using a light [[microscope]]. The terminology for who screens the sample varies according the country; in the [[UK]], the personnel are known as [[Cytoscreener]]s, [[Biomedical scientist]]s (BMS), [[Advanced Practitioner]]s and [[Pathologist]]s. The latter two take responsibility for reporting the abnormal sample which may require further investigation.
Studies of the accuracy of conventional cytology report:<ref name="pmid12676841"/>
* [[sensitivity (tests)|sensitivity]] 72%
* [[specificity (tests)|specificity]] 94%
In the [[United States]], [[physician]]s who fail to [[diagnose]] cervical cancer from a pap smear have been convicted of [[negligent homicide]]. In [[1988]] and [[1989]], Karen Smith had received pap smears which were argued to have "unequivocally" shown that she had cancer; yet the lab had not made the diagnosis. She died on [[March 8]] [[1995]]. Later, a physician and a laboratory technician were convicted of negligent homicide.{{Fact|date=April 2008}} These events have led to even more rigorous quality assurance programs, and to emphasizing that this is a screening, not a diagnostic, test, associated with a small irreducible error rate.
===Liquid based monolayer cytology===
Since the mid-1990s, techniques based around placing the sample into a vial containing a liquid medium which preserves the cells have been increasingly used. The media are primarily [[ethanol]] based. Two of the types are [[Sure-Path]] ([[TriPath Imaging]]) and [[Thin-Prep]] ([[Cytyc Corp]]).
Once placed into the vial, the sample is processed at the laboratory into a cell thin-layer, stained, and examined by light microscopy. The liquid sample has the advantage of being suitable for low and high risk HPV testing and reduced unsatisfactory specimens from 4.1% to 2.6%.<ref name="pmid17517761">{{cite journal |author=Ronco G, Cuzick J, Pierotti P, ''et al'' |title=Accuracy of liquid based versus conventional cytology: overall results of new technologies for cervical cancer screening randomised controlled trial |journal= BMJ|volume= 335|issue= |pages= 28|year=2007 |pmid=17517761 |doi=10.1136/bmj.39196.740995.BE}}</ref> Proper sample acquisition is crucial to the accuracy of the test; clearly, a cell that is not in the sample cannot be evaluated.
Studies of the accuracy of liquid based monolayer cytology report:
* [[sensitivity (tests)|sensitivity]] 61%<ref name="pmid12365959">{{cite journal |author=Kulasingam SL, Hughes JP, Kiviat NB, ''et al'' |title=Evaluation of human papillomavirus testing in primary screening for cervical abnormalities: comparison of sensitivity, specificity, and frequency of referral |journal=JAMA |volume=288 |issue=14 |pages=1749–57 |year=2002 |pmid=12365959 |doi=}}</ref> to 66%<ref name="pmid12676841"/>
* [[specificity (tests)|specificity]] 82%<ref name="pmid12365959"/> to 91%<ref name="pmid12676841"/>
Some<ref name="pmid17517761"/>, but not all studies<ref name="pmid12676841">{{cite journal |author=Coste J, Cochand-Priollet B, de Cremoux P, ''et al'' |title=Cross sectional study of conventional cervical smear, monolayer cytology, and human papillomavirus DNA testing for cervical cancer screening |journal=BMJ |volume=326 |issue=7392 |pages=733 |year=2003 |pmid=12676841 |doi=10.1136/bmj.326.7392.733}} [http://www.acpjc.org/Content/139/3/issue/ACPJC-2003-139-3-079.htm ACP Journal Club]</ref><ref name="pmid12365959"/>, report increased [[sensitivity (tests)|sensitivity]] from the liquid based smears.
===Human papillomavirus testing===
The presence of [[Human papillomavirus| HPV]] indicates that the person has been infected, the majority of women who get infected will successfully clear the infection within 18 months. It is those who have an infection of prolonged duration with high risk types<ref name="pmid16126875">{{cite journal |author=Cuschieri KS, Cubie HA, Whitley MW, ''et al'' |title=Persistent high risk HPV infection associated with development of cervical neoplasia in a prospective population study |journal=J. Clin. Pathol. |volume=58 |issue=9 |pages=946–50 |year=2005 |pmid=16126875 |doi=10.1136/jcp.2004.022863}}</ref> (e.g. types 16,18,31,45) that are more likely to develop Cervical Intraepithelial Neoplasia due to the effects that HPV has on DNA.
Studies of the accuracy of [[Human papillomavirus| HPV]] testing report:
* [[sensitivity (tests)|sensitivity]] 88% to 91% (for detecting CIN 3 or higher)<ref name="pmid12365959">{{cite journal |author=Kulasingam SL, Hughes JP, Kiviat NB, ''et al'' |title=Evaluation of human papillomavirus testing in primary screening for cervical abnormalities: comparison of sensitivity, specificity, and frequency of referral |journal=JAMA |volume=288 |issue=14 |pages=1749–57 |year=2002 |pmid=12365959 |doi=}}</ref> to 97% (for detecting CIN2+)<ref name="pmid14667741">{{cite journal |author=Cuzick J, Szarewski A, Cubie H, ''et al'' |title=Management of women who test positive for high-risk types of human papillomavirus: the HART study |journal=Lancet |volume=362 |issue=9399 |pages=1871–6 |year=2003 |pmid=14667741 |doi=}}</ref>
* [[specificity (tests)|specificity]] 73% to 79% (for detecting CIN 3 or higher)<ref name="pmid12365959"/> to 93% (for detecting CIN 3 or higher)<ref name="pmid14667741">{{cite journal |author=Cuzick J, Szarewski A, Cubie H, ''et al'' |title=Management of women who test positive for high-risk types of human papillomavirus: the HART study |journal=Lancet |volume=362 |issue=9399 |pages=1871–6 |year=2003 |pmid=14667741 |doi=}}</ref>
By adding the more [[specificity (tests)|sensitive]] HPV Test, the [[specificity (tests)|specificity]] may decline. However, the drop in specificity is not definite. <ref name="pmid14970277">{{cite journal |author=Arbyn M, Buntinx F, Van Ranst M, Paraskevaidis E, Martin-Hirsch P, Dillner J |title=Virologic versus cytologic triage of women with equivocal Pap smears: a meta-analysis of the accuracy to detect high-grade intraepithelial neoplasia |journal=J. Natl. Cancer Inst. |volume=96 |issue=4 |pages=280–93 |year=2004 |pmid=14970277 |doi=}}</ref> If the [[specificity (tests)|specificity]] does decline, this results in increased numbers of false positive tests and many women who did not have disease having colposcopy<ref>[http://screening.iarc.fr/colpochap.php?lang=1&chap=4 Colposcopy and Treatment of Cervical Intraepithelial Neoplasia: A Beginner's Manual<!-- Bot generated title -->]</ref> and treatment. A worthwhile [[Screening (medicine)|screening]] test requires a balance between the [[sensitivity (tests)|sensitivity]] and [[specificity (tests)|specificity]] to ensure that those having a disease are correctly identified as having it and equally importantly those not identifying those without the disease as having it. Due to the liquid based pap smears having a false negative rate of 15-35%, the [[American College of Obstetricians and Gynecologists]]{{Fact|article|date=June 2007}} and [http://www.asccp.org/ American Society for Colposcopy and Cervical Pathology]<ref name="pmid11966387">{{cite journal |author=Wright TC, Cox JT, Massad LS, Twiggs LB, Wilkinson EJ |title=2001 Consensus Guidelines for the management of women with cervical cytological abnormalities |journal=JAMA |volume=287 |issue=16 |pages=2120–9 |year=2002 |pmid=11966387 |doi=}}</ref> have recommended the use of [[Human papillomavirus| HPV]] testing in addition to the pap smear in all women over the age of 30.
Regarding the role of [[Human papillomavirus| HPV]] testing, [[randomized controlled trials]] have compared [[Human papillomavirus| HPV]] to [[colposcopy]]. [[Human papillomavirus| HPV]] testing appears as [[sensitivity (tests)|sensitive]] as immediate [[colposcopy]] while reducing the number of colposcopies needed.<ref name="pmid12824967">{{cite journal |author=ASCUS-LSIL Traige Study (ALTS) Group. |title=Results of a randomized trial on the management of cytology interpretations of atypical squamous cells of undetermined significance |journal=Am. J. Obstet. Gynecol. |volume=188 |issue=6 |pages=1383–92 |year=2003 |pmid=12824967 |doi=}}</ref> [[Randomized controlled trial]] have suggested that [[Human papillomavirus| HPV]] testing could follow abnormal cytology<ref name="pmid12365959"/> or could precede cervical cytology examination.<ref name="pmid14667741"/>
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>
===Automated analysis===
In the last decade there have been successful attempts to develop automated, computer image analysis systems for screening.<ref name="pmid15842055">{{cite journal |author=Biscotti CV, Dawson AE, Dziura B, ''et al'' |title=Assisted primary screening using the automated ThinPrep Imaging System |journal=Am. J. Clin. Pathol. |volume=123 |issue=2 |pages=281–7 |year=2005 |pmid=15842055 |doi=}}</ref> Automation may improve [[sensitivity (tests)|sensitivity]] and reduce unsatisfactory specimens.<ref name="pmid17604301">{{cite journal |author=Davey E, d'Assuncao J, Irwig L, ''et al'' |title=Accuracy of reading liquid based cytology slides using the ThinPrep Imager compared with conventional cytology: prospective study |journal= BMJ|volume= 335|issue= |pages= 31|year=2007 |pmid=17604301 |doi=10.1136/bmj.39219.645475.55}}</ref> One of these has been FDA approved and functions in high volume reference laboratories, with human oversight.{{Fact|article|date=July 2007}}
==Practical aspects==
The physician or operator collecting a sample for the test inserts a [[speculum (medical)|speculum]] into the patient's vagina, to obtain a cell sample from the [[cervix]]. A pap smear appointment is normally not scheduled during menstruation. The procedure is not usually painful, just a little uncomfortable. Results usually take about 3 weeks. Slight bleeding, cramps, and other discomfort can occur afterwards.
Other tests, including the TruTest, an [[endometrial biopsy]] used for early detection of [[uterine cancer]], can be performed during the same visit.
==References==
{{reflist}}
==External links==
* [http://www.jotrust.co.uk/about_cervical_cancer/screening.cfm Jo's Trust] - UK's leading cervical cancer charity.
* [http://www.imaginis.com/womenshealth/pap_smear.asp Imaginis - Pap Smear information]
* [http://screening.iarc.fr/cervicalindex.php?PHPSESSID=bdf4118e9fbfa65699927273a689bf8f/ International Agency for Research on Cancer] - Resource about screening, including that of Cervical Cancer. There are digital atlases of coloscopy, histology and cytology, the rationale of screening and setting up of a screening programme.
* [http://www.cancer.gov/cancertopics/factsheet/Detection/Pap-test The Pap Test: Questions and Answers — National Cancer Institute] — from the U.S.'s [[National Cancer Institute]]
* [http://www.emedicinehealth.com/articles/12373-1.asp Pap Smear] — from eMedicineHealth
* [http://medlineplus.nlm.nih.gov/medlineplus/cervicalcancer.html#preventionscreening MedlinePlus: Cervical Cancer Prevention/Screening] — from [[MedlinePlus]]
* The [http://bethesda2001.cancer.gov/ Bethesda 2001 Workshop], held April 30 - May 2, 2001, reviewed issues regarding terminology and reporting of cervical cytology
* [http://www.cytopathology.org/NIH/ NCI Bethesda System Web Atlas], with 349 images of different Pap smear morphologic findings — from the [[American Society of Cytopathology]]
*[http://www.hpvinfo.ca/hpvinfo/professionals/guidelines.aspx Canadian Guidelines for Cervical Cancer Screening] - Society of Obstetricians and Gynaecologists of Canada
* The UK's [http://nac.org.uk/ National Association of Cytologists]
* [http://www.clinicalcytology.co.uk/ British Society for Clinical Cytology]
* [http://www.ibms.org/index.cfm?method=science.cellular_pathology/ IBMS — The Institute of Biomedical Science] on cellular pathology
* [http://www.cancerscreening.nhs.uk/cervical/index.html NHS Cervical Screening Programme] — from the UK's [[National Health Service]]
* [http://www.engenderhealth.org/ia/swh/pccccs.html EngenderHealth- Cervical Cancer Screening]
* [http://www.obgyn.ufl.edu/obgyn101/Videos/Pelvic%20Exam.mpg Video of taking a smear using a wooden tool] - from University of Florida, Department of Obstetrics and Gynecology
* [http://www.obgyn.ufl.edu/obgyn101/Videos/Pap.mpg Video of taking a smear using a brush] - from University of Florida, Department of Obstetrics and Gynecology
[[Category:Oncology]]
[[Category:Gynecology]]
[[Category:Medical tests]]
[[Category:Papillomavirus]]
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