Editing Cervical cancer (section)

==Treatment==
[[File:Cervical Cryotherapy.png|thumb|Cervical cryotherapy]]
The treatment of cervical cancer varies worldwide, largely due to access to surgeons skilled in radical pelvic surgery and the emergence of fertility-sparing therapy in developed nations. Less advanced stages of cervical cancer typically have treatment options that allow fertility to be maintained if the patient desires.<ref>{{Cite web|title=Cervical Cancer Treatment Options {{!}} Treatment Choices by Stage|url=https://www.cancer.org/cancer/cervical-cancer/treating/by-stage.html|access-date=12 September 2020|website=www.cancer.org}}</ref>

Because cervical cancers are radiosensitive, radiation may be used in all stages where surgical options do not exist. Surgical intervention may have better outcomes than radiological approaches.<ref name="BaalbergenVeenstra2013">{{cite journal | vauthors = Baalbergen A, Veenstra Y, Stalpers L | title = Primary surgery versus primary radiotherapy with or without chemotherapy for early adenocarcinoma of the uterine cervix | journal = The Cochrane Database of Systematic Reviews | volume = 2021 | issue = 1 | pages = CD006248 | date = January 2013 | pmid = 23440805 | pmc = 7387233 | doi = 10.1002/14651858.CD006248.pub3 }}</ref> In addition, chemotherapy can be used to treat cervical cancer and is more effective than radiation alone.<ref>{{cite journal | vauthors = Einhorn N, Tropé C, Ridderheim M, Boman K, Sorbe B, Cavallin-Ståhl E | title = A systematic overview of radiation therapy effects in cervical cancer (cervix uteri) | journal = Acta Oncologica | volume = 42 | issue = 5–6 | pages = 546–556 | date = 2003 | pmid = 14596512 | doi = 10.1080/02841860310014660 | doi-access = free }}</ref> Chemoradiotherapy may increase overall survival and reduce the risk of disease recurrence compared to radiotherapy alone.<ref>{{cite journal | title = Reducing uncertainties about the effects of chemoradiotherapy for cervical cancer: individual patient data meta-analysis | journal = The Cochrane Database of Systematic Reviews | issue = 1 | pages = CD008285 | date = January 2010 | pmid = 20091664 | pmc = 7105912 | doi = 10.1002/14651858.cd008285 | author1 = Chemoradiotherapy for Cervical Cancer Meta-analysis Collaboration (CCCMAC) | volume = 2010 }}</ref>

Precancerous cells ([[cervical intraepithelial neoplasia]]) that would lead to cancer and early-stage cervical cancer (IA1) can be treated effectively by various surgical techniques. Surgical treatment methods include excision, where a [[Cervical conization|cone-shaped portion]] of the cervix is removed, and ablation which removes only the parts with abnormal tissues. While these effectively reduce the risk of cancer developing or spreading, they cause an increased risk of [[Preterm birth|premature birth]] in future pregnancies. Surgical techniques that remove more cervical tissue come with less risk of the cancer recurring but a higher chance of giving birth prematurely. Due to this risk, taking into account the age, childbearing plans of the woman, and the size and location of the cancer cells are crucial for choosing the right procedure.<ref name=":1" /><ref name=":2" /> There is low-certainty evidence that peri-operative care approaches, such as 'fast-track surgery' or 'enhanced recovery programmes' may lower surgical stress and improve recovery after gynaecological cancer surgery.<ref>{{cite journal |vauthors=Chau JP, Liu X, Lo SH, Chien WT, Hui SK, Choi KC, Zhao J |date=March 2022 |title=Perioperative enhanced recovery programmes for women with gynaecological cancers |journal=The Cochrane Database of Systematic Reviews |volume=2022 |issue=3 |pages=CD008239 |doi=10.1002/14651858.CD008239.pub5 |pmc=8922407 |pmid=35289396}}</ref>

Microinvasive cancer (stage IA) may also be treated by [[hysterectomy]] (removal of the whole uterus, including part of the [[vagina]]).<ref>{{cite journal | vauthors = van Nagell JR, Greenwell N, Powell DF, Donaldson ES, Hanson MB, Gay EC | title = Microinvasive carcinoma of the cervix | journal = American Journal of Obstetrics and Gynecology | volume = 145 | issue = 8 | pages = 981–991 | date = April 1983 | pmid = 6837683 | doi = 10.1016/0002-9378(83)90852-9 }}</ref> For stage IA2, the [[lymph node]]s are removed as well. Alternatives include local surgical procedures such as a [[loop electrical excision procedure]] <!-- (LEEP) --> or [[Cervical conization|cone biopsy]].<ref>{{cite web | vauthors = Erstad S | title=Cone biopsy (conization) for abnormal cervical cell changes | date=12 January 2007 | website=[[WebMD]] | url=http://www.webmd.com/cancer/cervical-cancer/cone-biopsy-conization-for-abnormal-cervical-cell-changes | access-date=2 December 2007 | url-status=live | archive-url=https://web.archive.org/web/20071119114319/http://www.webmd.com/cancer/cervical-cancer/cone-biopsy-conization-for-abnormal-cervical-cell-changes | archive-date=19 November 2007 }}</ref><ref name="LinZhou2017">{{cite journal | vauthors = Lin Y, Zhou J, Dai L, Cheng Y, Wang J | title = Vaginectomy and vaginoplasty for isolated vaginal recurrence 8 years after cervical cancer radical hysterectomy: A case report and literature review | journal = The Journal of Obstetrics and Gynaecology Research | volume = 43 | issue = 9 | pages = 1493–1497 | date = September 2017 | pmid = 28691384 | doi = 10.1111/jog.13375 | s2cid = 42161609 }}</ref> A systematic review concluded that more evidence is needed to inform decisions about different surgical techniques for women with cervical cancer at stage IA2.<ref>{{cite journal | vauthors = Kokka F, Bryant A, Brockbank E, Jeyarajah A | title = Surgical treatment of stage IA2 cervical cancer | journal = The Cochrane Database of Systematic Reviews | issue = 5 | pages = CD010870 | date = May 2014 | volume = 2018 | pmid = 24874726 | pmc = 6513277 | doi = 10.1002/14651858.cd010870.pub2 }}</ref>

If a cone biopsy does not produce clear margins<ref name=pmid8244170>{{cite journal | vauthors = Jones WB, Mercer GO, Lewis JL, Rubin SC, Hoskins WJ | title = Early invasive carcinoma of the cervix | journal = Gynecologic Oncology | volume = 51 | issue = 1 | pages = 26–32 | date = October 1993 | pmid = 8244170 | doi = 10.1006/gyno.1993.1241 }}</ref> (findings on biopsy showing that the tumor is surrounded by cancer free tissue, suggesting all of the tumor is removed), one more possible treatment option for women who want to preserve their fertility is a [[trachelectomy]].<ref>{{cite web |url=http://www.baymoon.com/~gyncancer/library/glossary/bldeftrachelect.htm |title=Trachelectomy |access-date=2 December 2007 | vauthors = Dolson L |year=2001 |archive-url=https://web.archive.org/web/20070927143641/http://www.baymoon.com/~gyncancer/library/glossary/bldeftrachelect.htm |archive-date=27 September 2007 }}</ref> This attempts to surgically remove the cancer while preserving the ovaries and uterus, providing for a more conservative operation than a hysterectomy. It is a viable option for those in stage I cervical cancer which has not spread; however, it is not yet considered a standard of care,<ref name=pmid16493253>{{cite journal | vauthors = Burnett AF | title = Radical trachelectomy with laparoscopic lymphadenectomy: review of oncologic and obstetrical outcomes | journal = Current Opinion in Obstetrics & Gynecology | volume = 18 | issue = 1 | pages = 8–13 | date = February 2006 | pmid = 16493253 | doi = 10.1097/01.gco.0000192968.75190.dc | s2cid = 22958941 }}</ref> as few doctors are skilled in this procedure. Even the most experienced surgeon cannot promise that a trachelectomy can be performed until after surgical microscopic examination, as the extent of the spread of cancer is unknown. If the surgeon is not able to microscopically confirm clear margins of cervical tissue once the woman is under general anaesthesia in the operating room, a hysterectomy may still be needed. This can only be done during the same operation if the woman consented. Due to the possible risk of cancer spreading to the lymph nodes in stage 1B cancers and some stage 1A cancers, the surgeon may also need to remove some lymph nodes from around the uterus for pathologic evaluation.{{citation needed|date=September 2017}}

A radical trachelectomy can be performed abdominally<ref name=pmid15918265>{{cite journal | vauthors = Cibula D, Ungár L, Svárovský J, Zivný J, Freitag P | title = [Abdominal radical trachelectomy--technique and experience] | language = cs | journal = Ceska Gynekologie | volume = 70 | issue = 2 | pages = 117–122 | date = March 2005 | pmid = 15918265 }}</ref> or vaginally<ref name=pmid15936061>{{cite journal | vauthors = Plante M, Renaud MC, Hoskins IA, Roy M | title = Vaginal radical trachelectomy: a valuable fertility-preserving option in the management of early-stage cervical cancer. A series of 50 pregnancies and review of the literature | journal = Gynecologic Oncology | volume = 98 | issue = 1 | pages = 3–10 | date = July 2005 | pmid = 15936061 | doi = 10.1016/j.ygyno.2005.04.014 }}</ref> and opinions are conflicting as to which is better.<ref name=pmid8812529>{{cite journal | vauthors = Roy M, Plante M, Renaud MC, Têtu B | title = Vaginal radical hysterectomy versus abdominal radical hysterectomy in the treatment of early-stage cervical cancer | journal = Gynecologic Oncology | volume = 62 | issue = 3 | pages = 336–339 | date = September 1996 | pmid = 8812529 | doi = 10.1006/gyno.1996.0245 }}</ref> A radical abdominal trachelectomy with lymphadenectomy usually only requires a two- to three-day hospital stay, and most women recover very quickly (about six weeks). Complications are uncommon, although women who can conceive after surgery are susceptible to preterm labour and possible late miscarriage.<ref name=pmid10760765>{{cite journal | vauthors = Dargent D, Martin X, Sacchetoni A, Mathevet P | title = Laparoscopic vaginal radical trachelectomy: a treatment to preserve the fertility of cervical carcinoma patients | journal = Cancer | volume = 88 | issue = 8 | pages = 1877–1882 | date = April 2000 | pmid = 10760765 | doi = 10.1002/(SICI)1097-0142(20000415)88:8<1877::AID-CNCR17>3.0.CO;2-W | doi-access = free }}</ref> A wait of at least one year is generally recommended before attempting to become pregnant after surgery.<ref name=pmid12548192>{{cite journal | vauthors = Schlaerth JB, Spirtos NM, Schlaerth AC | title = Radical trachelectomy and pelvic lymphadenectomy with uterine preservation in the treatment of cervical cancer | journal = American Journal of Obstetrics and Gynecology | volume = 188 | issue = 1 | pages = 29–34 | date = January 2003 | pmid = 12548192 | doi = 10.1067/mob.2003.124 }}</ref> Recurrence in the residual cervix is rare if the trachelectomy has cleared the cancer.<ref name=pmid16493253/> Yet, women are recommended to practice vigilant prevention and follow-up care, including Pap screenings/[[colposcopy]], with biopsies of the remaining lower uterine segment as needed (every 3–4 months for at least 5 years) to monitor for any recurrence in addition to minimizing any new exposures to HPV through [[safe sex]] practices until one is actively trying to conceive.{{citation needed|date=September 2017}}

Early stages (IB1 and IIA less than 4&nbsp;cm) can be treated with radical hysterectomy with removal of the lymph nodes or [[radiation therapy]]. Radiation therapy is given as external beam radiotherapy to the pelvis and [[brachytherapy]] (internal radiation). Women treated with surgery who have high-risk features found on pathologic examination are given radiation therapy with or without chemotherapy to reduce the risk of relapse.{{citation needed|date=September 2017}}  A Cochrane review has found moderate-certainty evidence that radiation decreases the risk of disease progression in people with stage IB cervical cancer when compared to no further treatment.<ref name = "Rogers_2012">{{cite journal | vauthors = Rogers L, Siu SS, Luesley D, Bryant A, Dickinson HO | title = Radiotherapy and chemoradiation after surgery for early cervical cancer | journal = The Cochrane Database of Systematic Reviews | issue = 5 | pages = CD007583 | date = May 2012 | volume = 5 | pmid = 22592722 | pmc = 4171000 | doi = 10.1002/14651858.cd007583.pub3 }}</ref> However, little evidence was found on its effects on overall survival.<ref name = "Rogers_2012" />
[[File:Diagram showing the position of the applicators for internal radiotherapy for cervical cancer CRUK 344.svg|thumb|right|Brachytherapy for cervical cancer]]

Larger early-stage tumors (IB2 and IIA more than 4&nbsp;cm) may be treated with radiation therapy and [[cisplatin]]-based chemotherapy, hysterectomy (which then usually requires [[adjuvant]] radiation therapy), or cisplatin chemotherapy followed by hysterectomy. When cisplatin is present, it is thought to be the most active single agent in periodic diseases.<ref>{{cite journal | vauthors = Waggoner SE | title = Cervical cancer | journal = Lancet | volume = 361 | issue = 9376 | pages = 2217–2225 | date = June 2003 | pmid = 12842378 | doi = 10.1016/S0140-6736(03)13778-6 | s2cid = 24115541 }}</ref> Such addition of platinum-based chemotherapy to chemoradiation seems not only to improve survival but also reduces risk of recurrence in women with early-stage cervical cancer (IA2–IIA).<ref>{{cite journal | vauthors = Falcetta FS, Medeiros LR, Edelweiss MI, Pohlmann PR, Stein AT, Rosa DD | title = Adjuvant platinum-based chemotherapy for early stage cervical cancer | journal = The Cochrane Database of Systematic Reviews | volume = 11 | pages = CD005342 | date = November 2016 | issue = 11 | pmid = 27873308 | pmc = 4164460 | doi = 10.1002/14651858.CD005342.pub4 }}</ref> A Cochrane review found a lack of evidence on the benefits and harms of primary hysterectomy compared to primary chemoradiotherapy for cervical cancer in stage IB2.<ref>{{cite journal | vauthors = Nama V, Angelopoulos G, Twigg J, Murdoch JB, Bailey J, Lawrie TA | title = Type II or type III radical hysterectomy compared to chemoradiotherapy as a primary intervention for stage IB2 cervical cancer | journal = The Cochrane Database of Systematic Reviews | volume = 2018 | issue = 10 | pages = CD011478 | date = October 2018 | pmid = 30311942 | pmc = 6516889 | doi = 10.1002/14651858.cd011478.pub2 }}</ref>

Advanced-stage tumors (IIB-IVA) are treated with radiation therapy and cisplatin-based chemotherapy. On 15 June 2006, the US [[Food and Drug Administration]] approved the use of a combination of two chemotherapy drugs, [[hycamtin]] and cisplatin, for women with late-stage (IVB) cervical cancer treatment.<ref>{{cite news | title=FDA Approves First Drug Treatment for Late-Stage Cervical Cancer | date=15 June 2006 | publisher=[[Food and Drug Administration|U.S. Food and Drug Administration]] | url=https://www.fda.gov/bbs/topics/NEWS/2006/NEW01391.html | access-date=2 December 2007 | url-status=live | archive-url=https://web.archive.org/web/20071010035641/https://www.fda.gov/bbs/topics/NEWS/2006/NEW01391.html | archive-date=10 October 2007 }}</ref> Combination treatment has significant risk of [[neutropenia]], [[anemia]], and [[thrombocytopenia]] side effects.<ref>{{cite journal | vauthors = Moon JY, Song IC, Ko YB, Lee HJ | title = The combination of cisplatin and topotecan as a second-line treatment for patients with advanced/recurrent uterine cervix cancer | journal = Medicine | volume = 97 | issue = 14 | pages = e0340 | date = April 2018 | pmid = 29620661 | pmc = 5902288 | doi = 10.1097/MD.0000000000010340 }}</ref>

There is insufficient evidence of whether anticancer drugs after standard care help women with locally advanced cervical cancer to live longer.<ref>{{cite journal | vauthors = Tangjitgamol S, Katanyoo K, Laopaiboon M, Lumbiganon P, Manusirivithaya S, Supawattanabodee B | title = Adjuvant chemotherapy after concurrent chemoradiation for locally advanced cervical cancer | journal = The Cochrane Database of Systematic Reviews | issue = 12 | pages = CD010401 | date = December 2014 | volume = 2019 | pmid = 25470408 | pmc = 6402532 | doi = 10.1002/14651858.cd010401.pub2 }}</ref>

For surgery to be curative, the entire cancer must be removed with no cancer found at the margins of the removed tissue on examination under a microscope.<ref name="Sar2015" /> This procedure is known as exenteration.<ref name="Sar2015">{{cite journal | vauthors = Sardain H, Lavoue V, Redpath M, Bertheuil N, Foucher F, Levêque J | title = Curative pelvic exenteration for recurrent cervical carcinoma in the era of concurrent chemotherapy and radiation therapy. A systematic review | journal = European Journal of Surgical Oncology | volume = 41 | issue = 8 | pages = 975–985 | date = August 2015 | pmid = 25922209 | doi = 10.1016/j.ejso.2015.03.235 | s2cid = 21911045 | url = https://hal-univ-rennes1.archives-ouvertes.fr/hal-01147372/file/Curative%20Pelvic%20Exenteration%20For%20Recurrent%20Cervical.pdf }}</ref>

No evidence is available to suggest that any form of follow-up approach is better or worse in terms of prolonging survival, improving quality of life, or guiding the management of problems that can arise because of the treatment and that in the case of radiotherapy treatment worsen with time.<ref>{{cite journal | vauthors = Lanceley A, Fiander A, McCormack M, Bryant A | title = Follow-up protocols for women with cervical cancer after primary treatment | journal = The Cochrane Database of Systematic Reviews | issue = 11 | pages = CD008767 | date = November 2013 | volume = 2014 | pmid = 24277645 | doi = 10.1002/14651858.CD008767.pub2 | pmc = 8969617 | collaboration = Cochrane Gynaecological, Neuro-oncology and Orphan Cancer Group }}</ref> A 2019 review found no controlled trials regarding the efficacy and safety of interventions for vaginal bleeding in women with advanced cervical cancer.<ref>{{cite journal | vauthors = Eleje GU, Eke AC, Igberase GO, Igwegbe AO, Eleje LI | title = Palliative interventions for controlling vaginal bleeding in advanced cervical cancer | journal = The Cochrane Database of Systematic Reviews | volume = 3 | issue = 3 | pages = CD011000 | date = March 2019 | pmid = 30888060 | pmc = 6423555 | doi = 10.1002/14651858.cd011000.pub3 }}</ref>

Immunotherapy with immune checkpoint inhibitors, such as [[pembrolizumab]] (Keytruda), has also been approved by the U.S. Food and Drug Administration (FDA) for certain patients with recurrent or metastatic cervical cancer, demonstrating promising results in ongoing clinical trials. <ref>{{cite web |url=https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pembrolizumab-advanced-cervical-cancer |title=FDA Approves Pembrolizumab for Advanced Cervical Cancer |publisher=U.S. Food and Drug Administration |date=12 June 2018 |access-date=12 January 2025 |archive-url=https://web.archive.org/web/20220110000000/https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pembrolizumab-advanced-cervical-cancer |archive-date=10 January 2022}}</ref><ref>{{cite journal |vauthors=Colomban L, Le Tourneau C |title=Immunotherapy in Cervical Cancer: Advances and Perspectives |journal=Cancers (Basel) |volume=14 |issue=15 |pages=3803 |date=July 2022 |pmid=35955074 |doi=10.3390/cancers14153803 |doi-access=free |pmc=9330146}}</ref> In October 2021, the FDA expanded this approval to include pembrolizumab in combination with chemotherapy, with or without [[bevacizumab]], for people with persistent, recurrent, or metastatic cervical cancer, underscoring the potential of immunotherapeutic approaches in this setting. <ref>{{cite web |url=https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pembrolizumab-cervical-cancer-new-dosing-regimen |title=FDA Approves Pembrolizumab for Cervical Cancer with a New Dosing Regimen |publisher=U.S. Food and Drug Administration |date=13 October 2021 |access-date=12 January 2025 |archive-url=https://web.archive.org/web/20220110000000/https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pembrolizumab-cervical-cancer-new-dosing-regimen |archive-date=10 January 2022}}</ref> Additional immunotherapy agents, including other PD-1 and PD-L1 inhibitors, are under investigation and have similarly shown encouraging outcomes in clinical studies.

Another immune checkpoint inhibitor, [[cemiplimab-rwlc]] (Libtayo), received FDA approval in September 2022 for patients with recurrent or metastatic cervical cancer that has progressed on or after chemotherapy, further highlighting the expanding role of immunotherapeutic strategies in advanced disease. <ref>{{cite web |url=https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-cemiplimab-rwlc-recurrent-or-metastatic-cervical-cancer-disease-progression-or-after-chemotherapy |title=FDA Approves Cemiplimab-rwlc for Recurrent or Metastatic Cervical Cancer with Disease Progression on or after Chemotherapy |publisher=U.S. Food and Drug Administration |date=29 September 2022 |access-date=12 January 2025 |archive-url=https://web.archive.org/web/20230101000000/https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-cemiplimab-rwlc-recurrent-or-metastatic-cervical-cancer-disease-progression-or-after-chemotherapy |archive-date=1 January 2023}}</ref>

[[Tisotumab vedotin]] (Tivdak) was approved for medical use in the United States in September 2021.<ref name="Tivdak FDA label">{{Cite web|url=https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/761208s000lbl.pdf|title=Enforcement Reports|access-date=21 September 2021|archive-date=21 September 2021|archive-url=https://web.archive.org/web/20210921051657/https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/761208s000lbl.pdf}}</ref><ref name="Seagen PR">{{cite web | title=Seagen and Genmab Announce FDA Accelerated Approval for Tivdak (tisotumab vedotin-tftv) in Previously Treated Recurrent or Metastatic Cervical Cancer | publisher=Seagen | via=Business Wire | date=20 September 2021 | url=https://www.businesswire.com/news/home/20210920005921/en/ | access-date=20 September 2021}}</ref>

<gallery>
File:Diagram showing the area removed with a posterior exenteration for cancer of the cervix CRUK 288.svg|Diagram showing the area removed with a posterior surgery
File:Diagram showing the area removed with a total exenteration operation for cancer of the cervix CRUK 289.svg|Diagram showing the area removed with a total operation
File:Diagram showing the area removed with an anterior exenteration operation for cancer of the cervix CRUK 290.svg|Diagram showing the area removed with an anterior operation
</gallery>