Editing Cervical cancer (section)

==Diagnosis==
[[File:Ca cervicis uteri T2 SAG.jpg|thumb|Cervical cancer seen on a T2-weighted sagittal MR image of the pelvis]]

===Biopsy===
The [[Pap test]] can be used as a [[Screening (medicine)|screening test]] but produces a [[False positives and false negatives#False negative error|false negative]] in up to 50% of cases of cervical cancer.<ref>Cecil Medicine: Expert Consult Premium Edition. {{ISBN|1-4377-3608-4}}, 9781437736083. Page 1317.</ref><ref>Berek and Hacker's Gynecologic Oncology. {{ISBN|0-7817-9512-5}}, 9780781795128. Page 342</ref> Another concern is the cost of doing Pap tests, which makes them unaffordable in many areas of the world.<ref>{{cite journal | vauthors = Cronjé HS | title = Screening for cervical cancer in developing countries | journal = International Journal of Gynaecology and Obstetrics | volume = 84 | issue = 2 | pages = 101–108 | date = February 2004 | pmid = 14871510 | doi = 10.1016/j.ijgo.2003.09.009 | s2cid = 21356776 }}</ref>

Confirmation of the diagnosis of cervical cancer or precancer requires a biopsy of the cervix. This is often done through [[colposcopy]], a magnified visual inspection of the cervix aided by using a dilute [[acetic acid]] (e.g. [[vinegar]]) solution to highlight abnormal cells on the surface of the cervix,<ref name=Robbins/> with visual contrast provided by staining the normal tissues a mahogany brown with Lugol's iodine.<ref>{{cite book | vauthors = Sellors JW |title=Colposcopy and treatment of cervical intraepithelial neoplasia: a beginners' manual |date=2003 |isbn=978-92-832-0412-1 |chapter-url=http://screening.iarc.fr/colpochap.php?lang=1&chap=4 |chapter=Chapter 4: An introduction to colposcopy: indications for colposcopy, instrumentation, principles and documentation of results|publisher=International Agency for Research on Cancer }}</ref> Medical devices used for biopsy of the cervix include [[Instruments used in obstetrics and gynecology|punch forceps]]. Colposcopic impression, the estimate of disease severity based on the visual inspection, forms part of the diagnosis. Further diagnostic and treatment procedures are [[loop electrical excision procedure]] and [[cervical conization]], in which the inner lining of the cervix is removed to be examined pathologically. These are carried out if the biopsy confirms severe [[cervical intraepithelial neoplasia]].<ref name=":1">{{cite journal | vauthors = Athanasiou A, Veroniki AA, Efthimiou O, Kalliala I, Naci H, Bowden S, Paraskevaidi M, Arbyn M, Lyons D, Martin-Hirsch P, Bennett P, Paraskevaidis E, Salanti G, Kyrgiou M | display-authors = 6 | title = Comparative effectiveness and risk of preterm birth of local treatments for cervical intraepithelial neoplasia and stage IA1 cervical cancer: a systematic review and network meta-analysis | journal = The Lancet. Oncology | volume = 23 | issue = 8 | pages = 1097–1108 | date = August 2022 | pmid = 35835138 | pmc = 9630146 | doi = 10.1016/S1470-2045(22)00334-5 }}</ref><ref name=":2">{{Cite journal |date=2023-11-10 |title=Prevention of cervical cancer: what are the risks and benefits of different treatments? |url=https://evidence.nihr.ac.uk/alert/prevention-of-cervical-cancer-what-are-the-risks-and-benefits-of-different-treatments/ |journal=NIHR Evidence |type=Plain English summary |publisher=National Institute for Health and Care Research |doi=10.3310/nihrevidence_60599|s2cid=265201829 }}</ref>

[[File:Squamous carcinoma of the cervix.jpg|right|thumb|This large squamous carcinoma (bottom of the picture) has obliterated the cervix and invaded the lower uterine segment. The uterus also has a round [[leiomyoma]] up higher.]]

Often before the biopsy, the doctor asks for medical imaging to rule out other causes of a woman's symptoms. Imaging modalities such as [[ultrasound]], CT scan, and MRI have been used to look for alternating disease, spread of the tumor, and effect on adjacent structures. Typically, they appear as heterogeneous masses on the cervix.<ref>{{cite journal | vauthors = Pannu HK, Corl FM, Fishman EK | title = CT evaluation of cervical cancer: spectrum of disease | journal = Radiographics | volume = 21 | issue = 5 | pages = 1155–1168 | date = September–October 2001 | pmid = 11553823 | doi = 10.1148/radiographics.21.5.g01se311155 }}</ref>

Interventions such as playing music during the procedure and viewing the procedure on a monitor can reduce the anxiety associated with the examination.<ref>{{cite journal | vauthors = Galaal K, Bryant A, Deane KH, Al-Khaduri M, Lopes AD | title = Interventions for reducing anxiety in women undergoing colposcopy | journal = The Cochrane Database of Systematic Reviews | volume = 2022 | issue = 12 | pages = CD006013 | date = December 2011 | pmid = 22161395 | pmc = 4161490 | doi = 10.1002/14651858.cd006013.pub3 }}</ref>

===Precancerous lesions===
[[IMage:Ca in situ, cervix 2.jpg|thumb|Histopathologic image ([[H&E stain]]) of carcinoma ''in situ'' (also called CIN3), stage 0: The normal architecture of stratified squamous epithelium is replaced by irregular cells that extend throughout its full thickness. Normal columnar epithelium is also seen.]]
[[Cervical intraepithelial neoplasia]] (CIN) means the development of abnormal cells on the surface of the cervix. It is caused by an HPV infection but in most cases, it is resolved by the immune system. However, a small percentage of people might develop a more serious CIN which, if left untreated, can develop into cervical cancer.<ref>{{cite book | vauthors = Mello V, Sundstrom RK | chapter = Cervical Intraepithelial Neoplasia |date=2023 | chapter-url = http://www.ncbi.nlm.nih.gov/books/NBK544371/ | title = StatPearls |access-date=2023-11-16 |place=Treasure Island (FL) |publisher=StatPearls Publishing |pmid=31335091 }}</ref><ref name=":3">{{Cite web |title=Cervical Dysplasia: Causes, Symptoms, Diagnosis & Treatment |url=https://my.clevelandclinic.org/health/diseases/15678-cervical-intraepithelial-neoplasia-cin |access-date=2023-11-16 |website=Cleveland Clinic |language=en}}</ref> CIN is often diagnosed during routine Pap smear examination or colposcopy.<ref name=":3" />

The naming and [[histology|histologic]] classification of cervical carcinoma precursor lesions has changed many times over the 20th century. The [[World Health Organization]] classification system was descriptive of the lesions, naming them mild, moderate, or severe [[dysplasia]] or [[carcinoma in situ|carcinoma ''in situ'']] (CIS).<ref name="CAresearchUK" /><ref name="DeMay">{{cite book |title=Practical principles of cytopathology. Revised edition. |vauthors=DeMay M |publisher=American Society for Clinical Pathology Press |year=2007 |isbn=978-0-89189-549-7 |location=Chicago, IL}}</ref> The term cervical intraepithelial neoplasia (CIN) was developed to place emphasis on the spectrum of abnormality in these lesions, and to help standardize treatment.<ref name=DeMay/> For premalignant dysplastic changes, cervical intraepithelial neoplasia grading  (CIN 1–3) is used. It classifies mild dysplasia as CIN1, moderate dysplasia as CIN2, and severe dysplasia and CIS as CIN3.<ref>{{cite book | vauthors = Salcedo MP, Phoolcharoen N, Schmeler KM | chapter = Intraepithelial neoplasia of the lower genital tract (cervix, vagina, vulva) |date=2022 | title = Comprehensive Gynecology |pages=637–647.e2 |publisher=Elsevier |language=en |doi=10.1016/b978-0-323-65399-2.00038-3 |isbn=978-0-323-65399-2 }}</ref> More recently, CIN2 and CIN3 have been combined into CIN2/3.  These results are what a pathologist might report from a biopsy.{{citation needed|date=September 2020}}

These should not be confused with the [[Bethesda system]] terms for Pap test ([[cytopathology]]) results.  Among the Bethesda results: [[Bethesda system|Low-grade squamous intraepithelial lesion]] (LSIL) and [[Bethesda system#HSIL|high-grade squamous intraepithelial lesion]] (HSIL). An LSIL Pap may correspond to CIN1, and HSIL may correspond to CIN2 and CIN3,<ref name=DeMay/> but they are results of different tests, and the Pap test results need not match the histologic findings.{{medical citation needed|date=May 2021}}

===Cancer subtypes===
[[Histopathology|Histologic]] subtypes of invasive cervical carcinoma include:<ref>{{cite web |url=http://www.emedicine.com/med/topic324.htm#section~workup |title=Cervical Cancer |access-date=2 December 2007 |vauthors=Garcia A, Hamid O, El-Khoueiry A |date=6 July 2006 |work=eMedicine |publisher=[[WebMD]] |url-status=live |archive-url=https://web.archive.org/web/20071209093214/http://www.emedicine.com/med/TOPIC324.HTM#section~workup |archive-date=9 December 2007 }}</ref><ref>{{cite news | vauthors = Dolinsky C |title=Cervical Cancer: The Basics |date=17 July 2006 |publisher=[[University of Pennsylvania|Abramson Cancer Center of the University of Pennsylvania]] | url=http://www.oncolink.upenn.edu/types/article.cfm?c=6&s=17&ss=129&id=8226 | work=OncoLink | access-date=2 December 2007 | archive-url=https://web.archive.org/web/20080118175524/http://www.oncolink.upenn.edu/types/article.cfm?c=6&s=17&ss=129&id=8226 | archive-date=18 January 2008 }}</ref>
* [[Squamous cell carcinoma]] (about 80–85%<ref>{{cite web|title=What Is Cervical Cancer?|url=https://www.cancer.org/cancer/cervical-cancer/about/what-is-cervical-cancer.html|publisher=American Cancer Society}}</ref><ref>{{cite web|title=Cervical cancer – Types and grades|url=http://www.cancerresearchuk.org/about-cancer/cervical-cancer/stages-types-grades/types-and-grades|publisher=Cancer Research UK}}</ref>)
* [[adenocarcinoma]] (about 15% of cervical cancers in the UK<ref name=CAresearchUK>{{cite web |title = Cancer Research UK website |url = http://info.cancerresearchuk.org/cancerstats/types/cervix/incidence/ |access-date = 3 January 2009 |archive-url = https://web.archive.org/web/20090116222837/http://info.cancerresearchuk.org/cancerstats/types/cervix/incidence/ |archive-date = 16 January 2009 }}</ref>)
* [[Adenosquamous carcinoma]]
* [[Small cell carcinoma]]
* [[Neuroendocrine tumour]]
* [[Glassy cell carcinoma of the cervix|Glassy cell carcinoma]]
* [[Villoglandular adenocarcinoma of the cervix|Villoglandular adenocarcinoma]]
<gallery mode="packed" heights="160">
Image:Histopathology of squamous cell carcinoma of the cervix.png|Invasive squamous cell carcinoma of the cervix is characterized by infiltration as irregular anastomosing nests or single cells.<ref>{{cite web | vauthors = Turashvili G | title = Squamous cell carcinoma and variants | website= Pathology Outlines |url= https://www.pathologyoutlines.com/topic/cervixscc.html }}</ref> This case is poorly differentiated. H&E stain.
File:Immunohistochemistry for p16 in cervical squamous cell carcinoma.jpg|Cervical squamous cell carcinoma generally shows diffuse staining of both nuclei and cytoplasm on [[p16]] [[Immunohistochemistry|immuno-<br />histochemistry]] (except verrucous variant).<ref>Image by Mikael Häggström, MD. Source for caption: {{cite web|url=https://www.pathologyoutlines.com/topic/cervixscc.html|title=Cervix - Squamous cell carcinoma and variants|website=Pathology Outlines|vauthors=Turashvili G}} Last author update: 24 September 2020</ref>
File:Invasive cervical squamous cell carcinoma on H&E histopathology and Ki-67 immunohistochemistry.jpg|Invasive cervical squamous cell carcinoma on H&E histopathology and Ki-67 immunohistochemistry. The latter correlates well with the degree and level of dysplasia.<ref>Image by Mikael Häggström, MD. Source for caption: {{cite journal|vauthors=Ghosh A, Nirupama M, Padmanabha N, Kini H| title=Assessment of p16 and Ki67 Immunohistochemistry Expression in Squamous Intraepithelial Lesion with Cytohistomorphological Correlation. | journal=Iran J Pathol | year= 2020 | volume= 15 | issue= 4 | pages= 268–273 | pmid=32944038 | doi=10.30699/ijp.2020.112421.2208 | pmc=7477676 }}</ref>
Image:Cervix quadrants and directions.svg|The location of cervical cancer can be described in terms of quadrants, or corresponding to a [[clock face]] when the subject is in [[supine position]].
</gallery>

Though squamous cell carcinoma is the cervical cancer with the most incidence, the incidence of adenocarcinoma of the cervix has been increasing in recent decades.<ref name=Robbins/> Endocervical adenocarcinoma represents 20–25% of the histological types of cervical carcinoma. Gastric-type mucinous adenocarcinoma of the cervix is a rare type of cancer with aggressive behavior. This type of malignancy is not related to high-risk human papillomavirus (HPV).<ref>{{cite journal |vauthors = Mulita F, Iliopoulos F, Kehagias I |title = A rare case of gastric-type mucinous endocervical adenocarcinoma in a 59-year-old woman |journal = Przeglad Menopauzalny = Menopause Review |volume = 19 |issue = 3 |pages = 147–150 |date = September 2020 |pmid = 33100952 |pmc = 7573334 |doi = 10.5114/pm.2020.99563 }}</ref>
Noncarcinoma malignancies which can rarely occur in the cervix include [[melanoma]] and [[lymphoma]].  The [[International Federation of Gynecology and Obstetrics]] (FIGO) stage does not incorporate [[lymph node]] involvement in contrast to the [[TNM staging system|TNM]] staging for most other cancers. For cases treated surgically, information obtained from the pathologist can be used in assigning a separate pathologic stage but is not to replace the original clinical stage.{{citation needed|date=September 2020}}

===Staging===
{{Main|Cervical cancer staging}}
Cervical cancer is staged by the FIGO system, which is based on clinical examination rather than surgical findings. Before the 2018 revisions to FIGO staging, the system allowed only these diagnostic tests to be used in determining the stage: palpation, inspection, [[colposcopy]], endocervical [[curettage]], [[hysteroscopy]], [[cystoscopy]], [[proctoscopy]], intravenous [[urography]], and [[X-ray]] examination of the lungs and skeleton, and cervical [[conization]]. However, the system allows use of any imaging or pathological methods for staging.<ref>{{cite journal |vauthors = Bhatla N, Berek JS, Cuello Fredes M, Denny LA, Grenman S, Karunaratne K, Kehoe ST, Konishi I, Olawaiye AB, Prat J, Sankaranarayanan R, Brierley J, Mutch D, Querleu D, Cibula D, Quinn M, Botha H, Sigurd L, Rice L, Ryu HS, Ngan H, Mäenpää J, Andrijono A, Purwoto G, Maheshwari A, Bafna UD, Plante M, Natarajan J |display-authors = 6 |title = Revised FIGO staging for carcinoma of the cervix uteri |journal = International Journal of Gynaecology and Obstetrics |volume = 145 |issue = 1 |pages = 129–135 |date = April 2019 |pmid = 30656645 |doi = 10.1002/ijgo.12749 |s2cid = 58656013 }}</ref>

<gallery>
File:Diagram showing stage 1A cervical cancer CRUK 200.svg|Stage 1A cervical cancer
File:Diagram showing stage 1B cervical cancer CRUK 203.svg|Stage 1B cervical cancer
File:Diagram showing stage 2A cervical cancer CRUK 212.svg|Stage 2A cervical cancer
File:Diagram showing stage 2B cervical cancer CRUK 216.svg|Stage 2B cervical cancer
File:Diagram showing stage 3B cervical cancer CRUK 226.svg|Stage 3B cervical cancer
File:Diagram showing stage 4A cervical cancer CRUK 236.svg|Stage 4A cervical cancer
File:Diagram showing stage 4B cervical cancer CRUK 239.svg|Stage 4B cervical cancer
</gallery>