Cervical cancer screening: Difference between revisions

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| [[File:Siren.gif|30px|link=Cancer screening resident survival guide]]|| <br> || <br>
| [[Cancer screening resident survival guide|'''Resident'''<br>'''Survival'''<br>'''Guide''']]
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{{Cervical cancer}}
{{Cervical cancer}}
{{CMG}}; '''Assistant Editor-in-Chief:''' [[User:Sarthak|Sarthak Sachdeva]]
{{CMG}}; '''Assistant Editor-in-Chief:''' {{Nnasiri}}{{MD}}
 


==Overview==
==Overview==
[[Pap smear]] is a medical [[screening]] method, invented by [[Georgios Papanikolaou]], primarily designed to detect premalignant and malignant processes in the [[ectocervix]]. It may also detect [[infection]]s and abnormalities in the endocervix and [[endometrium]].
According to the [[American Cancer Society]] (ACS) (the American Society for Colposcopy and Cervical Pathology (ASCCP), and American Society for Clinical Pathology participated in the 2021 update<ref name="pmid22422631">{{cite journal| author=Saslow D, Solomon D, Lawson HW, Killackey M, Kulasingam SL, Cain J | display-authors=etal| title=American Cancer Society, American Society for Colposcopy and Cervical Pathology, and American Society for Clinical Pathology screening guidelines for the prevention and early detection of cervical cancer. | journal=CA Cancer J Clin | year= 2012 | volume= 62 | issue= 3 | pages= 147-72 | pmid=22422631 | doi=10.3322/caac.21139 | pmc=3801360 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22422631  }} </ref> but did not participate in this update):
==Procedure==
[[Image:200px-Gray1167.svg.png|left]]
The 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.
It is generally recommended that sexually active females seek Pap smear testing annually, although guidelines may vary from country to country. 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 (or even as an alternative) to Pap testing.
 
About 5% to 7% of pap smears produce abnormal results, 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 or (more frequently with the advent of liquid-based cytology) a plastic-fronded broom. 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 can not 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 Cytoscreeners, [[Biomedical scientist]]s (BMS), Advanced Practitioners and [[Pathologist]]s. The latter two take responsibility for reporting the abnormal sample which may require further investigation.  
"individuals with a cervix initiate cervical cancer screening at age 25 years and undergo primary human papillomavirus (HPV) testing every 5 years through age 65 years (preferred); if primary HPV testing is not available, then individuals aged 25 to 65 years should be screened with cotesting (HPV testing in combination with cytology) every 5 years or cytology alone every 3 years (acceptable) (strong recommendation).."<ref name="pmid32729638">{{cite journal| author=Fontham ETH, Wolf AMD, Church TR, Etzioni R, Flowers CR, Herzig A | display-authors=etal| title=Cervical cancer screening for individuals at average risk: 2020 guideline update from the American Cancer Society. | journal=CA Cancer J Clin | year= 2020 | volume= 70 | issue= 5 | pages= 321-346 | pmid=32729638 | doi=10.3322/caac.21628 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32729638  }} </ref>


Studies of the accuracy of conventional cytology report:
Importantly, self-sampling HPV testing is not yet approved by the FDA although this is a priority of the "Last Mile" initiative of the National Cancer Institute<ref>https://prevention.cancer.gov/major-programs/nci-cervical-cancer-last-mile-initiative</ref>
* [[sensitivity (tests)|Sensitivity]] 72%<ref name="pmid12676841"/>
* [[specificity (tests)|Specificity]] 94%<ref name="pmid12676841"/>
 
==Liquid Based Monolayer Cytology==
The 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= |volume= |issue= |pages= |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.
 
==Results==
[[Image:320px-Low-grade sil and endocx.jpg|thumb|left|[[Micrograph]] of a '''Pap test''' showing a low-grade intraepithelial lesion (LSIL) and benign [[endocervix|endocervical]] mucosa. [[Pap stain]].]]
 
[[Image:Trichomonas pap test.jpg|thumb|left|[[Micrograph]] of a '''Pap test''' showing [[trichomoniasis]]. Trichomonas organism seen in the upper right. [[Pap stain]].]]
 
[[Image:310px-Herpes simplex virus pap test.jpg|thumb|left|[[Micrograph]] of a '''Pap test''' showing changes of [[herpes simplex virus]]. [[Pap stain]].]]
'''The Bethesda system''' ('''TBS''') is a system for reporting [[cervix|cervical]] or vaginal [[Cytopathology|cytologic]] diagnoses,<ref name="pmid14655809">{{cite journal| author=Apgar BS, Zoschnick L, Wright TC| title=The 2001 Bethesda System terminology. | journal=Am Fam Physician | year= 2003 | volume= 68 | issue= 10 | pages= 1992-8 | pmid=14655809 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14655809  }} </ref> used for reporting [[Pap smear]] results.
* '''Types of results'''
:* Abnormal results include
::* Atypical squamous cells
:::* Atypical squamous cells of undetermined significance (ASC-US)
:::* Atypical squamous cells – cannot exclude HSIL (ASC-H)
::* Low grade squamous intraepithelial lesion (LGSIL or LSIL)
::* High grade squamous intraepithelial lesion (HGSIL or HSIL)
::* [[Squamous cell carcinoma]]
::* Atypical Glandular Cells not otherwise specified (AGC-NOS)
::* Atypical Glandular Cells, suspicious for AIS or cancer (AGC-neoplastic)
::* Adenocarcinoma ''in situ'' (AIS)
 
==Effectiveness==
The Pap test, when combined with a regular program of screening and appropriate follow-up, can reduce cervical cancer deaths by up to 80%.<ref name=Arbyn10>{{cite journal| journal = Annals of Oncology | volume = 21 | pages = 448–458 | year = 2010| title = European Guidelines for Quality Assurance in Cervical Cancer Screening. Second Edition—Summary Document| pmid = 20176693 | author = M. Arbyn; et al.| pmc = 2826099 | issue = 3 | doi=10.1093/annonc/mdp471 }}</ref>
Failure of prevention of cancer by the Pap test can occur for many reasons, including not getting regular screening, lack of appropriate follow up of abnormal results, and sampling and interpretation errors.<ref name=DeMay>{{cite book| author = DeMay, M. | year = 2007 | title = Practical principles of cytopathology.  Revised edition. | isbn = 978-0-89189-549-7| publisher = American Society for Clinical Pathology Press| location = Chicago, IL}}</ref>  In the US, over half of all invasive cancers occur in women that have never had a Pap smear; an additional 10 to 20% of cancers occur in women that have not had a Pap smear in the preceding five years.  About one-quarter of US cervical cancers were in women that had an abnormal Pap smear, but did not get appropriate follow-up (woman did not return for care, or clinician did not perform recommended tests or treatment).
 
[[Adenocarcinoma]] of the cervix has not been shown to be prevented by Pap tests.<ref name=DeMay />  In the UK, which has a Pap smear screening program, Adenocarcinoma accounts for about 15% of all cervical cancers<ref>{{cite web| title=Cancer Research UK website | url = http://info.cancerresearchuk.org/cancerstats/types/cervix/incidence/ | accessdate = 2009-01-03}}</ref>
 
==Screening With the Pap Test: Harms==
Based on solid evidence, regular screening with the Pap test leads to additional diagnostic procedures (e.g., [[colposcopy]]) and treatment for low-grade squamous intraepithelial lesions ([[LSIL]]), with long-term consequences for fertility and pregnancy. These harms are greatest for younger women, who have a higher prevalence of LSIL, lesions that often regress without treatment. Harms are also increased in younger women because they have a higher rate of false-positive results.
Magnitude of Effect: Additional diagnostic procedures were performed in 50% of women undergoing regular Pap testing. Approximately 5% were treated for LSIL. The number with impaired fertility and pregnancy complications is unknown.
 
==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</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]] 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.
 
==Screening With the Human Papillomavirus (HPV) DNA Test: Benefits==
Based on solid evidence, screening with HPV DNA or HPV RNA detects high-grade [[cervical dysplasia]], a precursor lesion for cervical cancer. Additional clinical trials show that [[HPV testing]] is superior to other cervical cancer screening strategies. In April 2014, the U.S. Food and Drug Administration approved an HPV DNA test that can be used alone for the primary screening of cervical cancer risk in women aged 25 years and older.
Magnitude of Effect: In one prospective, clustered, randomized trial, HPV testing was superior to other strategies for preventing cervical cancer mortality. <ref>http://www.cancer.gov/types/cervical/hp/cervical-screening-pdq#link/_133_toc</ref>
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"/>
 
==Screening With the HPV DNA Test: Harms==
Based on solid evidence, HPV testing identifies numerous infections that will not lead to [[cervical dysplasia]] or cervical cancer. This is especially true in women younger than 30 years, in whom rates of HPV infection may be higher. In one study, 86.7 % of women with a positive [[HPV test]] did not develop cervical cancer or related premalignant disease after more than a decade of follow up.<ref>http://www.cancer.gov/types/cervical/hp/cervical-screening-pdq#link/_133_toc</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= |volume= |issue= |pages= |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.


==Screening==
The Pap test screening detects and prevents 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]] of the [[uterus]] and the endocervix.
It is generally recommended that sexually active females seek [[pap smear]] testing annually, although guidelines may vary from country to country. <ref>{{cite journal|journal=ecancermedicalscience|issn=17546605|doi=10.3332/ecancer.2012.258}}</ref><ref name="CurryKrist2018">{{cite journal|last1=Curry|first1=Susan J.|last2=Krist|first2=Alex H.|last3=Owens|first3=Douglas K.|last4=Barry|first4=Michael J.|last5=Caughey|first5=Aaron B.|last6=Davidson|first6=Karina W.|last7=Doubeni|first7=Chyke A.|last8=Epling|first8=John W.|last9=Kemper|first9=Alex R.|last10=Kubik|first10=Martha|last11=Landefeld|first11=C. Seth|last12=Mangione|first12=Carol M.|last13=Phipps|first13=Maureen G.|last14=Silverstein|first14=Michael|last15=Simon|first15=Melissa A.|last16=Tseng|first16=Chien-Wen|last17=Wong|first17=John B.|title=Screening for Cervical Cancer|journal=JAMA|volume=320|issue=7|year=2018|pages=674|issn=0098-7484|doi=10.1001/jama.2018.10897}}</ref><ref>{{cite journal|doi=10.1097/AOG.0000000000001708.}}</ref><ref name="HuhAult2015">{{cite journal|last1=Huh|first1=Warner K.|last2=Ault|first2=Kevin A.|last3=Chelmow|first3=David|last4=Davey|first4=Diane D.|last5=Goulart|first5=Robert A.|last6=Garcia|first6=Francisco A. R.|last7=Kinney|first7=Walter K.|last8=Massad|first8=L. Stewart|last9=Mayeaux|first9=Edward J.|last10=Saslow|first10=Debbie|last11=Schiffman|first11=Mark|last12=Wentzensen|first12=Nicolas|last13=Lawson|first13=Herschel W.|last14=Einstein|first14=Mark H.|title=Use of Primary High-Risk Human Papillomavirus Testing for Cervical Cancer Screening|journal=Obstetrics & Gynecology|volume=125|issue=2|year=2015|pages=330–337|issn=0029-7844|doi=10.1097/AOG.0000000000000669}}</ref><ref name="urlFinal Recommendation Statement: Cervical Cancer: Screening - US Preventive Services Task Force">{{cite web |url=https://www.uspreventiveservicestaskforce.org/Page/Document/RecommendationStatementFinal/cervical-cancer-screening2 |title=Final Recommendation Statement: Cervical Cancer: Screening - US Preventive Services Task Force |format= |work= |accessdate=}}</ref><ref name="urlPractice Advisory: Cervical Cancer Screening (Update) - ACOG">{{cite web |url=https://www.acog.org/Clinical-Guidance-and-Publications/Practice-Advisories/Practice-Advisory-Cervical-Cancer-Screening-Update |title=Practice Advisory: Cervical Cancer Screening (Update) - ACOG |format= |work= |accessdate=}}</ref>
*


==Screening Guidelines==
==Screening Guidelines==
 
{| style="border: 0px; font-size: 90%; margin: 3px;" align="center"
{| style="border: 0px; font-size: 90%; margin: 3px;" align=center
|-
|-
! colspan=2 style="padding: 5px 5px; background: #4479BA; color:#FFF; width: 10%;" |
! colspan="2" style="padding: 5px 5px; background: #4479BA; color:#FFF; width: 10%;" |
! style="padding: 5px 5px; background: #4479BA; color:#FFF; width: 30%;" |'''American Cancer Society (ACS), American Society for Colposcopy and Cervical Pathology (ASCCP), and American Society for Clinical Pathology '''
! style="padding: 5px 5px; background: #4479BA; color:#FFF; width: 30%;" |'''American Cancer Society (ACS), American Society for Colposcopy and Cervical Pathology (ASCCP), and American Society for Clinical Pathology '''
! style="padding: 5px 5px; background: #4479BA; color:#FFF; width: 30%;" |'''U.S. Preventive Services Task Force (USPSTF)'''  
2012 version (has since been updated in 2020
! style="padding: 5px 5px; background: #4479BA; color:#FFF; width: 30%;" |'''U.S. Preventive Services Task Force (USPSTF)'''
2018 guidelines
! style="padding: 5px 5px; background: #4479BA; color:#FFF; width: 30%;" |'''American College of Obstetricians and Gynecologists (ACOG)'''
! style="padding: 5px 5px; background: #4479BA; color:#FFF; width: 30%;" |'''American College of Obstetricians and Gynecologists (ACOG)'''
|-
|-
| colspan=2 style="padding: 5px 5px; background: #DCDCDC;" | When to start screening
! colspan="2" style="padding: 5px 5px; background: #DCDCDC;" | When to start screening
| style="padding: 5px 5px; background: #F5F5F5;" | Age 21. Women aged <21 years should not be screened regardless of the age of sexual initiation or other risk factors
| style="padding: 5px 5px; background: #F5F5F5;" | Age 21. Women aged <21 years should not be screened regardless of the age of sexual initiation or other risk factors
| style="padding: 5px 5px; background: #F5F5F5;" | Age 21. (A recommendation) Recommend against screening women aged <21 years (D recommendation)
| style="padding: 5px 5px; background: #F5F5F5;" | Age 21. (A recommendation) Recommend against screening women aged <21 years (D recommendation)
| style="padding: 5px 5px; background: #F5F5F5;" | Age 21 regardless of the age of onset of sexual activity. Women aged <21 years should not be screened regardless of age at sexual initiation and other behavior-related risk factors (Level A evidence)
| style="padding: 5px 5px; background: #F5F5F5;" | Age 21 regardless of the age of onset of sexual activity. Women aged <21 years should not be screened regardless of age at sexual initiation and other behavior-related risk factors (Level A evidence)
|-
|-
| colspan=2 style="padding: 5px 5px; background: #DCDCDC;" | Statement about annual screening  
! colspan="2" style="padding: 5px 5px; background: #DCDCDC;" | Statement about annual screening  
| style="padding: 5px 5px; background: #F5F5F5;" | Women of any age should not be screened annually by any screening method
| style="padding: 5px 5px; background: #F5F5F5;" | Women of any age should not be screened annually by any screening method
| style="padding: 5px 5px; background: #F5F5F5;" | Individuals and clinicians can use the annual Pap test screening visit as an opportunity to discuss other health problems and preventive measures. Individuals, clinicians, and health systems should seek effective ways to facilitate the receipt of recommended preventive services at intervals that are beneficial to the patient. Efforts also should be made to ensure that individuals are able to seek care for additional health concerns as they present
| style="padding: 5px 5px; background: #F5F5F5;" | Individuals and clinicians can use the annual [[Pap test]] screening visit as an opportunity to discuss other health problems and preventive measures. Individuals, clinicians, and health systems should seek effective ways to facilitate the receipt of recommended preventive services at intervals that are beneficial to the patient. Efforts also should be made to ensure that individuals are able to seek care for additional health concerns as they present
| style="padding: 5px 5px; background: #F5F5F5;" | In women aged 30–65 years, annual cervical cancer screening should not be performed. (Level A evidence) Patients should be counseled that annual well-woman visits are recommended even if cervical cancer screening is not performed at each visit
| style="padding: 5px 5px; background: #F5F5F5;" | In women aged 30–65 years, annual cervical cancer screening should not be performed. (Level A evidence) Patients should be counseled that annual well-woman visits are recommended even if cervical cancer screening is not performed at each visit
|-
|-
| colspan=2 style="padding: 5px 5px; background: #DCDCDC;" | Screening method and intervals
! colspan="2" style="padding: 5px 5px; background: #DCDCDC;" | Screening method and intervals
| colspan=3 style="padding: 5px 5px; background: #F5F5F5;" |  
| colspan="3" style="padding: 5px 5px; background: #F5F5F5;" |  
|-
|-
| rowspan=2 style="padding: 5px 5px; background: #DCDCDC;" | Cytology (conventional or liquid based)
! rowspan="2" style="padding: 5px 5px; background: #DCDCDC;" | [[Cytology]] (conventional or liquid based)
| style="padding: 5px 5px; background: #DCDCDC;" | 21–29 years
! style="padding: 5px 5px; background: #DCDCDC;" | 21–29 years
| style="padding: 5px 5px; background: #F5F5F5;" | Every 3 years
| style="padding: 5px 5px; background: #F5F5F5;" | Every 3 years
| style="padding: 5px 5px; background: #F5F5F5;" | Every 3 years (A recommendation).
| style="padding: 5px 5px; background: #F5F5F5;" | Every 3 years (A recommendation)  
| style="padding: 5px 5px; background: #F5F5F5;" | Every 3 years (Level A evidence).
| style="padding: 5px 5px; background: #F5F5F5;" | Every 3 years (Level A evidence)  
|-
|-
| style="padding: 5px 5px; background: #DCDCDC;" | 30–65 years
! style="padding: 5px 5px; background: #DCDCDC;" | 30–65 years
| style="padding: 5px 5px; background: #F5F5F5;" | Every 3 years
| style="padding: 5px 5px; background: #F5F5F5;" | Every 3 years
| style="padding: 5px 5px; background: #F5F5F5;" | Every 3 years (A recommendation).
| style="padding: 5px 5px; background: #F5F5F5;" | Every 3 years (A recommendation)  
| style="padding: 5px 5px; background: #F5F5F5;" | Every 3 years (Level A evidence).
| style="padding: 5px 5px; background: #F5F5F5;" | Every 3 years (Level A evidence)
|-
|-
| rowspan=2 style="padding: 5px 5px; background: #DCDCDC;" | HPV co-test (cytology + HPV test administered together)
! rowspan="2" style="padding: 5px 5px; background: #DCDCDC;" | HPV co-test (cytology + [[HPV test]] administered together)
| style="padding: 5px 5px; background: #DCDCDC;" | 21–29 years
! style="padding: 5px 5px; background: #DCDCDC;" | 21–29 years
| style="padding: 5px 5px; background: #F5F5F5;" | HPV co-testing should not be used for women aged <30 years  
| style="padding: 5px 5px; background: #F5F5F5;" | HPV co-testing should not be used for women aged <30 years  
| style="padding: 5px 5px; background: #F5F5F5;" | Recommend against HPV co-testing in women aged <30 years (D recommendation)
| style="padding: 5px 5px; background: #F5F5F5;" | Recommend against [[HPV]] co-testing in women aged <30 years (D recommendation)
| style="padding: 5px 5px; background: #F5F5F5;" | HPV co-testinge should not be performed in women aged <30 years. (Level A evidence )
| style="padding: 5px 5px; background: #F5F5F5;" | [[HPV]] co-testing should not be performed in women aged <30 years. (Level A evidence )
|-
|-
| style="padding: 5px 5px; background: #DCDCDC;" | 30–65 years
! style="padding: 5px 5px; background: #DCDCDC;" | 30–65 years
| style="padding: 5px 5px; background: #F5F5F5;" | Every 5 years; this is the preferred method.
| style="padding: 5px 5px; background: #F5F5F5;" | Every 5 years; this is the preferred method.
| style="padding: 5px 5px; background: #F5F5F5;" | For women who want to extend their screening interval, HPV co-testing every 5 years is an option (A recommendation)
| style="padding: 5px 5px; background: #F5F5F5;" | For women who want to extend their screening interval, HPV co-testing every 5 years is an option (A recommendation)
| style="padding: 5px 5px; background: #F5F5F5;" | Every 5 years; this is the preferred method (Level A evidence)
| style="padding: 5px 5px; background: #F5F5F5;" | Every 5 years; this is the preferred method (Level A evidence)
|-
|-
| colspan=2 style="padding: 5px 5px; background: #DCDCDC;" | Primary hrHPV f testing (as an alternative to cotesting or g cytology alone)
! colspan="2" style="padding: 5px 5px; background: #DCDCDC;" | Primary hrHPV f testing (as an alternative to cotesting or g cytology alone)
| style="padding: 5px 5px; background: #F5F5F5;" | For women aged 30–65 years, screening by HPV testing alone is not recommended in most clinical settings
| style="padding: 5px 5px; background: #F5F5F5;" | For women aged 30–65 years, screening by [[HPV]] testing alone is not recommended in most clinical settings
| style="padding: 5px 5px; background: #F5F5F5;" | Recommend against screening for cervical cancer with HPV testing (alone or in combination with cytology) in women aged <30 years (D recommendation)
| style="padding: 5px 5px; background: #F5F5F5;" | Recommend against screening for cervical cancer with HPV testing (alone or in combination with cytology) in women aged <30 years (D recommendation)
| style="padding: 5px 5px; background: #F5F5F5;" | Not addressed
| style="padding: 5px 5px; background: #F5F5F5;" | Not addressed
|-
|-
| colspan=2 style="padding: 5px 5px; background: #DCDCDC;" | When to stop screening  
! colspan="2" style="padding: 5px 5px; background: #DCDCDC;" | When to stop screening  
| style="padding: 5px 5px; background: #F5F5F5;" | Aged >65 years with adequate negative prior screening* and no history of CIN2 or higher within the last 20 years
| style="padding: 5px 5px; background: #F5F5F5;" | Aged >65 years with adequate negative prior screening and no history of [[CIN]]2 or higher within the last 20 years
| style="padding: 5px 5px; background: #F5F5F5;" | Aged >65 years with adequate screening history* and are not otherwise at high risk for cervical cancer (D recommendation)
| style="padding: 5px 5px; background: #F5F5F5;" | Aged >65 years with adequate screening history and are not otherwise at high risk for cervical [[cancer]] (D recommendation)
| style="padding: 5px 5px; background: #F5F5F5;" | Aged >65 years with adequate negative prior screening* results and no history of CIN 2 or higher (Level A evidence)
| style="padding: 5px 5px; background: #F5F5F5;" | Aged >65 years with adequate negative prior screening* results and no history of CIN 2 or higher (Level A evidence)
|-
|-
| colspan=2 style="padding: 5px 5px; background: #DCDCDC;" | When to screen after age 65 years  
! colspan="2" style="padding: 5px 5px; background: #DCDCDC;" | When to screen after age 65 years  
| style="padding: 5px 5px; background: #F5F5F5;" | When to screen after age 65 years Aged >65 years with a history of CIN2 CIN2, CIN3, or adenocarcinoma in situ, routine screeningk should continue for at least 20 years
| style="padding: 5px 5px; background: #F5F5F5;" | When to screen after age 65 years Aged >65 years with a history of [[CIN]]2 CIN2, CIN3, or [[adenocarcinoma]] in situ, routine screening should continue for at least 20 years
| style="padding: 5px 5px; background: #F5F5F5;" | Women aged >65 years who have never been screened, do not meet the criteria for adequate prior screening, or for whom the adequacy of prior screening cannot be accurately accessed or documented.l Routine screeningk should continue for at least 20 years after spontaneous regression or appropriate management of a high-grade precancerous lesion, even if this extends screening past age 65 years. Certain considerations may support screening in women aged > 65 years who are otherwise considered high risk (such as women with a highgrade precancerous lesion or cervical cancer, women with in utero exposure to diethylstilbestrol, or women who are immunocompromised)
| style="padding: 5px 5px; background: #F5F5F5;" | Women aged >65 years who have never been screened, do not meet the criteria for adequate prior screening, or for whom the adequacy of prior screening cannot be accurately accessed or documented. Routine screening should continue for at least 20 years after spontaneous regression or appropriate management of a high-grade precancerous lesion, even if this extends screening past age 65 years. Certain considerations may support screening in women aged > 65 years who are otherwise considered high risk (such as women with a highgrade precancerous lesion or cervical cancer, women with in utero exposure to diethylstilbestrol, or women who are [[immunocompromised]])
| style="padding: 5px 5px; background: #F5F5F5;" | Women aged >65 years with a history of CIN2, CIN3, or AIS should continue routine agebased screeningk for at least 20 years (Level B evidence)
| style="padding: 5px 5px; background: #F5F5F5;" | Women aged >65 years with a history of CIN2, [[CIN]]3, or [[AIS]] should continue routine agebased screeningk for at least 20 years (Level B evidence)
|-
|-
| colspan=2 style="padding: 5px 5px; background: #DCDCDC;" | Screening post-hysterectomy
! colspan="2" style="padding: 5px 5px; background: #DCDCDC;" | Screening post-[[hysterectomy]]
| style="padding: 5px 5px; background: #F5F5F5;" | Women who have had a total hysterectomy (removal of the uterus and cervix) should stop screening.m Women who have had a supra-cervical hysterectomy (cervix intact) should continue screening according to guidelines
| style="padding: 5px 5px; background: #F5F5F5;" | Women who have had a total [[hysterectomy]] (removal of the [[uterus]] and [[cervix]]) should stop screening. Women who have had a supra-cervical [[hysterectomy]] (cervix intact) should continue screening according to guidelines
| style="padding: 5px 5px; background: #F5F5F5;" | Recommend against screening in women who have had a hysterectomy (removal of the cervix)n (D recommendation)
| style="padding: 5px 5px; background: #F5F5F5;" | Recommend against screening in women who have had a [[hysterectomy]] (removal of the [[cervix]]) (D recommendation)
| style="padding: 5px 5px; background: #F5F5F5;" | Women who have had a hysterectomy (removal of the cervix) should stop screening and not restart for any reasonn,o (Level A evidence)
| style="padding: 5px 5px; background: #F5F5F5;" | Women who have had a [[hysterectomy]] (removal of the [[cervix]]) should stop screening and not restart for any reason, (Level A evidence)
|-
|-
| colspan=2 style="padding: 5px 5px; background: #DCDCDC;" | The need for a bimanual pelvic exam
! colspan="2" style="padding: 5px 5px; background: #DCDCDC;" | The need for a bimanual [[pelvic exam]]
| style="padding: 5px 5px; background: #F5F5F5;" | Not addressed in 2012 guidelines but was addressed in 2002 ACS guidelines
| style="padding: 5px 5px; background: #F5F5F5;" | Not addressed in 2012 guidelines but was addressed in 2002 ACS guidelines
| style="padding: 5px 5px; background: #F5F5F5;" | Addressed in USPSTF ovarian cancer screening recommendations (draft)
| style="padding: 5px 5px; background: #F5F5F5;" | Addressed in USPSTF ovarian cancer screening recommendations.
| style="padding: 5px 5px; background: #F5F5F5;" | Addressed in 2012 well-woman visit recommendations.r Aged <21 years, no evidence supports the routine internal examination of the healthy, asymptomatic patient. An “external-only” genital examination is acceptable. Aged ≥21 years, no evidence supports or refutes the annual pelvic examination or speculum and bimanual examination. The decision whether or not to perform a complete pelvic examination should be a shared decision after a discussion between the patient and her health care provider. Annual examination of the external genitalia should continue
| style="padding: 5px 5px; background: #F5F5F5;" | Aged <21 years, no evidence supports the routine internal examination of the healthy, asymptomatic patient. An “external-only” genital examination is acceptable. Aged ≥21 years, no evidence supports or refutes the annual [[pelvic]] examination or speculum and bimanual examination. The decision whether or not to perform a complete [[pelvic]] examination should be a shared decision after a discussion between the patient and her health care provider. Annual examination of the external genitalia should continue
|-
|-
| colspan=2 style="padding: 5px 5px; background: #DCDCDC;" | Screening among those immunized against HPV 16/18
! colspan="2" style="padding: 5px 5px; background: #DCDCDC;" | Screening among those immunized against [[HPV]] 16/18
| style="padding: 5px 5px; background: #F5F5F5;" | Women at any age with a history of HPV vaccination should be screened according to the age specific recommendations for the general population
| style="padding: 5px 5px; background: #F5F5F5;" | Women at any age with a history of [[HPV]] vaccination should be screened according to the age specific recommendations for the general population
| style="padding: 5px 5px; background: #F5F5F5;" | The possibility that vaccination might reduce the need for screening with cytology alone or in combination with HPV testing is not established. Given these uncertainties, women who have been vaccinated should continue to be screened
| style="padding: 5px 5px; background: #F5F5F5;" | The possibility that [[vaccination]] might reduce the need for screening with cytology alone or in combination with [[HPV]] testing is not established. Given these uncertainties, women who have been vaccinated should continue to be screened
| style="padding: 5px 5px; background: #F5F5F5;" | Women who have received the HPV vaccine should be screened according to the same guidelines as women who have not been vaccinated (Level C evidence)
| style="padding: 5px 5px; background: #F5F5F5;" | Women who have received the [[HPV]] vaccine should be screened according to the same guidelines as women who have not been vaccinated (Level C evidence)
|}
|}
HPV = human papillomavirus; CIN = cervical intraepithelial neoplasia; AIS=adenocarcinoma in situ; hrHPV = high-risk HPV.
HPV = human papillomavirus; CIN = cervical intraepithelial neoplasia; AIS=adenocarcinoma in situ; hrHPV = high-risk HPV.
==See also==
[[Colposcopy]]


==References==
==References==
{{reflist|2}}
{{reflist|2}}
{{WH}}
{{WS}}


[[Category:Disease]]
[[Category:Disease]]
[[Category:Gynecology]]
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[[Category:Types of cancer]]
[[Category:Types of cancer]]
[[Category:Needs overview]]
[[Category:Up-To-Date]]
[[Category:primary care]]
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[[Category:Medicine]]
{{WH}}
{{WS}}

Latest revision as of 19:46, 16 September 2023
Resident
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Cervical cancer Microchapters

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Assistant Editor-in-Chief: Nima Nasiri, M.D.[2]Monalisa Dmello, M.B,B.S., M.D. [3]

Overview

According to the American Cancer Society (ACS) (the American Society for Colposcopy and Cervical Pathology (ASCCP), and American Society for Clinical Pathology participated in the 2021 update[1] but did not participate in this update):

"individuals with a cervix initiate cervical cancer screening at age 25 years and undergo primary human papillomavirus (HPV) testing every 5 years through age 65 years (preferred); if primary HPV testing is not available, then individuals aged 25 to 65 years should be screened with cotesting (HPV testing in combination with cytology) every 5 years or cytology alone every 3 years (acceptable) (strong recommendation).."[2]

Importantly, self-sampling HPV testing is not yet approved by the FDA although this is a priority of the "Last Mile" initiative of the National Cancer Institute[3]

Screening

The Pap test screening detects and prevents the progression of HPV-induced cervical cancer and other abnormalities in the female genital tract by sampling cells from the outer opening of the cervix of the uterus and the endocervix. It is generally recommended that sexually active females seek pap smear testing annually, although guidelines may vary from country to country. [4][5][6][7][8][9]

Screening Guidelines

American Cancer Society (ACS), American Society for Colposcopy and Cervical Pathology (ASCCP), and American Society for Clinical Pathology

2012 version (has since been updated in 2020

U.S. Preventive Services Task Force (USPSTF)

2018 guidelines

American College of Obstetricians and Gynecologists (ACOG)
When to start screening Age 21. Women aged <21 years should not be screened regardless of the age of sexual initiation or other risk factors Age 21. (A recommendation) Recommend against screening women aged <21 years (D recommendation) Age 21 regardless of the age of onset of sexual activity. Women aged <21 years should not be screened regardless of age at sexual initiation and other behavior-related risk factors (Level A evidence)
Statement about annual screening Women of any age should not be screened annually by any screening method Individuals and clinicians can use the annual Pap test screening visit as an opportunity to discuss other health problems and preventive measures. Individuals, clinicians, and health systems should seek effective ways to facilitate the receipt of recommended preventive services at intervals that are beneficial to the patient. Efforts also should be made to ensure that individuals are able to seek care for additional health concerns as they present In women aged 30–65 years, annual cervical cancer screening should not be performed. (Level A evidence) Patients should be counseled that annual well-woman visits are recommended even if cervical cancer screening is not performed at each visit
Screening method and intervals
Cytology (conventional or liquid based) 21–29 years Every 3 years Every 3 years (A recommendation) Every 3 years (Level A evidence)
30–65 years Every 3 years Every 3 years (A recommendation) Every 3 years (Level A evidence)
HPV co-test (cytology + HPV test administered together) 21–29 years HPV co-testing should not be used for women aged <30 years Recommend against HPV co-testing in women aged <30 years (D recommendation) HPV co-testing should not be performed in women aged <30 years. (Level A evidence )
30–65 years Every 5 years; this is the preferred method. For women who want to extend their screening interval, HPV co-testing every 5 years is an option (A recommendation) Every 5 years; this is the preferred method (Level A evidence)
Primary hrHPV f testing (as an alternative to cotesting or g cytology alone) For women aged 30–65 years, screening by HPV testing alone is not recommended in most clinical settings Recommend against screening for cervical cancer with HPV testing (alone or in combination with cytology) in women aged <30 years (D recommendation) Not addressed
When to stop screening Aged >65 years with adequate negative prior screening and no history of CIN2 or higher within the last 20 years Aged >65 years with adequate screening history and are not otherwise at high risk for cervical cancer (D recommendation) Aged >65 years with adequate negative prior screening* results and no history of CIN 2 or higher (Level A evidence)
When to screen after age 65 years When to screen after age 65 years Aged >65 years with a history of CIN2 CIN2, CIN3, or adenocarcinoma in situ, routine screening should continue for at least 20 years Women aged >65 years who have never been screened, do not meet the criteria for adequate prior screening, or for whom the adequacy of prior screening cannot be accurately accessed or documented. Routine screening should continue for at least 20 years after spontaneous regression or appropriate management of a high-grade precancerous lesion, even if this extends screening past age 65 years. Certain considerations may support screening in women aged > 65 years who are otherwise considered high risk (such as women with a highgrade precancerous lesion or cervical cancer, women with in utero exposure to diethylstilbestrol, or women who are immunocompromised) Women aged >65 years with a history of CIN2, CIN3, or AIS should continue routine agebased screeningk for at least 20 years (Level B evidence)
Screening post-hysterectomy Women who have had a total hysterectomy (removal of the uterus and cervix) should stop screening. Women who have had a supra-cervical hysterectomy (cervix intact) should continue screening according to guidelines Recommend against screening in women who have had a hysterectomy (removal of the cervix) (D recommendation) Women who have had a hysterectomy (removal of the cervix) should stop screening and not restart for any reason, (Level A evidence)
The need for a bimanual pelvic exam Not addressed in 2012 guidelines but was addressed in 2002 ACS guidelines Addressed in USPSTF ovarian cancer screening recommendations. Aged <21 years, no evidence supports the routine internal examination of the healthy, asymptomatic patient. An “external-only” genital examination is acceptable. Aged ≥21 years, no evidence supports or refutes the annual pelvic examination or speculum and bimanual examination. The decision whether or not to perform a complete pelvic examination should be a shared decision after a discussion between the patient and her health care provider. Annual examination of the external genitalia should continue
Screening among those immunized against HPV 16/18 Women at any age with a history of HPV vaccination should be screened according to the age specific recommendations for the general population The possibility that vaccination might reduce the need for screening with cytology alone or in combination with HPV testing is not established. Given these uncertainties, women who have been vaccinated should continue to be screened Women who have received the HPV vaccine should be screened according to the same guidelines as women who have not been vaccinated (Level C evidence)

HPV = human papillomavirus; CIN = cervical intraepithelial neoplasia; AIS=adenocarcinoma in situ; hrHPV = high-risk HPV.

See also

Colposcopy

References

  1. ↑ Saslow D, Solomon D, Lawson HW, Killackey M, Kulasingam SL, Cain J; et al. (2012). "American Cancer Society, American Society for Colposcopy and Cervical Pathology, and American Society for Clinical Pathology screening guidelines for the prevention and early detection of cervical cancer". CA Cancer J Clin. 62 (3): 147–72. doi:10.3322/caac.21139. PMC 3801360. PMID 22422631.
  2. ↑ Fontham ETH, Wolf AMD, Church TR, Etzioni R, Flowers CR, Herzig A; et al. (2020). "Cervical cancer screening for individuals at average risk: 2020 guideline update from the American Cancer Society". CA Cancer J Clin. 70 (5): 321–346. doi:10.3322/caac.21628. PMID 32729638 Check |pmid= value (help).
  3. ↑ https://prevention.cancer.gov/major-programs/nci-cervical-cancer-last-mile-initiative
  4. ↑ ecancermedicalscience. doi:10.3332/ecancer.2012.258. ISSN 1754-6605. Missing or empty |title= (help)
  5. ↑ Curry, Susan J.; Krist, Alex H.; Owens, Douglas K.; Barry, Michael J.; Caughey, Aaron B.; Davidson, Karina W.; Doubeni, Chyke A.; Epling, John W.; Kemper, Alex R.; Kubik, Martha; Landefeld, C. Seth; Mangione, Carol M.; Phipps, Maureen G.; Silverstein, Michael; Simon, Melissa A.; Tseng, Chien-Wen; Wong, John B. (2018). "Screening for Cervical Cancer". JAMA. 320 (7): 674. doi:10.1001/jama.2018.10897. ISSN 0098-7484.
  6. ↑ . doi:10.1097/AOG.0000000000001708. Check |doi= value (help). Missing or empty |title= (help)
  7. ↑ Huh, Warner K.; Ault, Kevin A.; Chelmow, David; Davey, Diane D.; Goulart, Robert A.; Garcia, Francisco A. R.; Kinney, Walter K.; Massad, L. Stewart; Mayeaux, Edward J.; Saslow, Debbie; Schiffman, Mark; Wentzensen, Nicolas; Lawson, Herschel W.; Einstein, Mark H. (2015). "Use of Primary High-Risk Human Papillomavirus Testing for Cervical Cancer Screening". Obstetrics & Gynecology. 125 (2): 330–337. doi:10.1097/AOG.0000000000000669. ISSN 0029-7844.
  8. ↑ "Final Recommendation Statement: Cervical Cancer: Screening - US Preventive Services Task Force".
  9. ↑ "Practice Advisory: Cervical Cancer Screening (Update) - ACOG".

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