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Cervical Cancer

By

Pedro T. Ramirez

, MD, The University of Texas MD Anderson Cancer Center;


Gloria Salvo

, MD, MD Anderson Cancer Center

Last full review/revision Jul 2022| Content last modified Sep 2022
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Cervical cancer is usually a squamous cell carcinoma; less often, it is an adenocarcinoma. The cause of most cervical cancers is human papillomavirus infection. Cervical neoplasia is often asymptomatic; the first symptom of cervical cancer is usually irregular, often postcoital vaginal bleeding. Diagnosis is by a cervical Papanicolaou test and biopsy. Staging is clinical, combined with imaging and pathology results when available. Treatment usually involves surgical resection for early-stage disease or radiation therapy plus chemotherapy for locally advanced disease. If the cancer has widely metastasized, chemotherapy is often used alone.

Cervical cancer is the 3rd most common gynecologic cancer and the 8th most common cancer among women in the US. Mean age at diagnosis is 50; it is frequently diagnosed in women aged 35 to 44 years. The National Cancer Institute estimates that in 2021, there were 14,480 new cases of invasive cervical cancer and 4290 deaths (1 Arteries of the heart Arteries of the heart ). Worldwide, cervical cancer incidence and mortality are higher in low- or middle-income countries; rates are highest in sub-Saharan Africa. Among females, it is the most common cancer in 23 countries and the leading cause of cancer death in 36 countries (2 Arteries of the heart Arteries of the heart ).

Risk factors associated with cervical cancer include

The precursor to cervical cancer is cervical intraepithelial neoplasia (CIN). The great majority of cases of CIN and invasive cervical cancer are caused by persistent infection with human papillomavirus Human Papillomavirus (HPV) Infection Human papillomavirus (HPV) causes warts. Some types cause skin warts, and other types cause raised or flat genital warts (lesions of the skin or mucous membranes of the genitals). Infection... read more Human Papillomavirus (HPV) Infection (HPV), transmitted mainly through sexual activity. Most (70%) of precancerous and invasive disease can be directly attributed to HPV types 16 or 18; however, 99% of cervical cancer specimens contain DNA from a high-risk HPV genotype (3 Arteries of the heart Arteries of the heart , 4 Arteries of the heart Arteries of the heart ). The incidence of cervical cancer has decreased steadily over the past several decades because of HPV vaccination, cervical cancer screening, and treatment of CIN.

General references

  • 1. National Cancer Institute: Cancer Stat Facts: Cervical Cancer. Accessed 6/21/22.

  • 2. Sung H, Ferlay J, Siegel RL, et al: Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 71 (3):209–249, 2021. doi: 10.3322/caac.21660 Epub 2021 Feb 4.

  • 3. Joste NE, Ronnett BM, Hunt WC, et al: Human papillomavirus genotype-specific prevalence across the continuum of cervical neoplasia and cancer. Cancer Epidemiol Biomarkers Prev 24 (1): 230–240, 2015. doi: 10.1158/1055-9965.EPI-14-0775

  • 4. Walboomers JMM, Jacobs MV, Manos MM, et al: Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol 189 (1):12–19, 1999. doi: 10.1002/(SICI)1096-9896(199909)189:1<12::aid-path431>3.0.CO;2-F

Pathology of Cervical Cancer

The cervix is composed of stroma and epithelium. The ectocervix protrudes into the vagina and is lined with squamous epithelium. The endocervix (a canal that passes from the internal os to the external os) is lined with columnar epithelium. Nearly all cervical carcinomas originate in the transformation zone, which surrounds the external os; the transformation zone is an area of squamous metaplasia between the original and current squamocolumnar junction (1 Pathology reference Cervical cancer is usually a squamous cell carcinoma; less often, it is an adenocarcinoma. The cause of most cervical cancers is human papillomavirus infection. Cervical neoplasia is often asymptomatic... read more Pathology reference ).

Cervical intraepithelial neoplasia (CIN) is graded as

  • 1: Mild cervical dysplasia

  • 2: Moderate dysplasia

  • 3: Severe dysplasia and carcinoma in situ

CIN 3 is unlikely to regress spontaneously; if untreated, it may, over months or years, penetrate the basement membrane, becoming invasive carcinoma.

About 80 to 85% of all cervical cancers are squamous cell carcinoma; most of the rest are adenocarcinomas. Sarcomas and small cell neuroendocrine tumors are rare.

Invasive cervical cancer usually spreads by direct extension into surrounding tissues or via the lymphatics to the pelvic and para-aortic lymph nodes. Hematogenous spread is possible but rare.

If cervical cancer spreads to the pelvic or para-aortic lymph nodes, the prognosis is worse, and the location and size of the radiation therapy field is affected.

Pathology reference

Symptoms and Signs of Cervical Cancer

Early cervical cancer can be asymptomatic. When symptoms occur, they usually include irregular vaginal bleeding, which is most often postcoital, but may occur spontaneously between menses. Larger cancers are more likely to bleed spontaneously and may cause a foul-smelling vaginal discharge or pelvic pain. More widespread cancer may cause obstructive uropathy, back pain, and leg swelling due to venous or lymphatic obstruction.

Pelvic examination may detect an exophytic necrotic cervical tumor; however, most cervical cancers cannot be seen without magnification.

Diagnosis of Cervical Cancer

  • Papanicolaou (Pap) test (cervical cytology)

  • Biopsy

Cervical cancer may be suspected during a routine gynecologic examination. It is considered in women with

  • Visible cervical lesion

  • Abnormal vaginal bleeding

Cervical cancer is usually diagnosed when cervical cytology and/or HPV testing detects abnormalities. Reporting of cervical cytology results is standardized (see table Bethesda Classification of Cervical Cytology Bethesda Classification of Cervical Cytology* Bethesda Classification of Cervical Cytology* [ 1 Diagnosis references Cervical cancer is usually a squamous cell carcinoma; less often, it is an adenocarcinoma. The cause of most cervical cancers is human papillomavirus infection. Cervical neoplasia is often asymptomatic... read more Diagnosis references ]). Further evaluation with screening tests or colposcopy is indicated if atypical or cancerous cells are found and/or HPV testing is positive. Colposcopy (examination of the vagina and cervix with a magnifying lens) is used to identify areas that require biopsy; endocervical curettage is also often performed. Cone biopsy (conization) is required if the diagnosis is uncertain and high-grade CIN or invasive cancer is suspected; a cone of tissue is removed using a loop electrical excision procedure (LEEP), laser, or scalpel (cold knife).

Table

Staging

Cervical cancer staging underwent a major revision in 2018. The previous FIGO 2009 staging system allowed only clinical examination, cervical biopsy, and a few additional tests to assign the stage. The FIGO 2018 staging system allows, when available, cross-sectional imaging (eg, ultrasonography, CT, MRI, positron emission tomography [PET], PET-CT, MRI-PET) and surgical pathology results to supplement clinical findings in all stages. Imaging and pathology results are optional because they may be not available in low- and middle-income countries, where cervical cancer is more common (2 Diagnosis references Cervical cancer is usually a squamous cell carcinoma; less often, it is an adenocarcinoma. The cause of most cervical cancers is human papillomavirus infection. Cervical neoplasia is often asymptomatic... read more Diagnosis references , 3 Diagnosis references Cervical cancer is usually a squamous cell carcinoma; less often, it is an adenocarcinoma. The cause of most cervical cancers is human papillomavirus infection. Cervical neoplasia is often asymptomatic... read more Diagnosis references , 4 Diagnosis references Cervical cancer is usually a squamous cell carcinoma; less often, it is an adenocarcinoma. The cause of most cervical cancers is human papillomavirus infection. Cervical neoplasia is often asymptomatic... read more Diagnosis references ).

Other changes in the 2018 staging system include the following:

If the stage is > IA2, CT or MRI of the abdomen and pelvis is typically done to better determine tumor size, parametrial involvement, vaginal compromise, and nodal metastases. PET with CT (PET/CT) is often used to check for spread beyond the cervix. If PET/CT, MRI, or CT is not available, cystoscopy, sigmoidoscopy, chest x-ray, and IV urography, when clinically indicated, may be used for staging.

Table

When imaging tests suggest that pelvic or para-aortic lymph nodes are grossly enlarged (> 2 cm), surgical exploration, typically with a retroperitoneal approach, may be indicated. Its sole purpose is to remove enlarged lymph nodes so that radiation therapy can be more precisely targeted and more effective.

Diagnosis references

Prognosis for Cervical Cancer

The most common histologic types of cervical cancer (squamous cell carcinoma, adenocarcinoma) usually metastasize to distant sites only when the cancer is locally advanced or recurrent. The 5-year survival rates are as follows:

  • Stage I: 80 to 90%

  • Stage II: 60 to 75%

  • Stage III: 30 to 40%

  • Stage IV: 0 to 15%

Nearly 80% of recurrences manifest within 2 years.

Adverse prognostic factors include

  • Lymph node involvement

  • Large tumor size and volume

  • Deep cervical stromal invasion

  • Parametrial invasion

  • Lymphovascular space invasion (LVSI)

  • Nonsquamous histology

Treatment of Cervical Cancer

  • Surgery alone for microinvasive disease

  • Surgery or curative radiation therapy if there is no spread to parametria or beyond

  • Radiation therapy and chemotherapy (chemoradiation) if there is spread to parametria or beyond

  • Chemotherapy for metastatic and recurrent cancer

Treatment of cervical cancer may include surgery, radiation therapy, and chemotherapy. If radical hysterectomy is indicated but patients are not ideal candidates for it, chemoradiation is used and has similar oncologic outcomes.

Stage IA1 (no lymphovascular space invasion)

Treatment of stage IA1 involves

  • Conization or simple hysterectomy

Microinvasive cervical cancer, defined as FIGO stage IA1 with no lymphovascular space invasion (LVSI), has a < 1% risk of lymph node metastases and may be managed conservatively with conization using LEEP, laser, or cold knife. Conization is indicated for patients who are interested in preserving fertility (to obtain, if possible, a nonfragmented specimen with a 3-mm margin). A cold knife preserves the margins for pathology evaluation but cannot always be used.

Simple hysterectomy should be done if patients are not interested in preserving fertility or if margins are positive after conization. If margins are positive, sentinel lymph node (SLN) mapping should be considered, and if patients are interested in preserving fertility, repeat conization is an alternative.

Sentinel lymph node mapping for cervical cancer

Sentinel lymph node (SLN) mapping is an alternative to full pelvic lymphadenectomy for patients with early-stage (IA1 with lymphovascular space invasion, IB1, IB2, or IIA1) cervical cancer (1 Treatment references Cervical cancer is usually a squamous cell carcinoma; less often, it is an adenocarcinoma. The cause of most cervical cancers is human papillomavirus infection. Cervical neoplasia is often asymptomatic... read more Treatment references ) because only 15 to 20% of these patients have positive nodes. SLN mapping therefore decreases the number of full pelvic lymphadenectomies, which can have adverse effects (eg, lymphedema, nerve damage).

For SLN mapping, blue dye, technetium-99 (99Tc), or indocyanine green (ICG) is directly injected into the cervix, usually at 3 and 9 o’clock. During surgery, SLNs are identified by direct visualization of blue dye, by a camera to detect the fluorescence of ICG, or by a gamma probe to detect 99Tc. SLNs are commonly located medial to the external iliac vessels, ventral to the hypogastric vessels, or in the superior part of the obturator space.

Ultrastaging of all SLNs is done to detect micrometastasis and isolated tumor cells (low-volume disease). Any grossly suspicious node must be removed regardless of mapping. If there is no mapping on a hemipelvis, a side-specific lymphadenectomy is done. In the 2018 FIGO staging system, only macrometastases and micrometastases are considered when classifying cases as IIIC; isolated tumor cells do not change the stage, they are considered pN0.

Detection rates for SLN mapping are best for tumors < 2 cm.

Stage IA1 (with lymphovascular space invasion) and stage IA2

For stage IA1 with LVSI or stage IA2, recommended treatments include

  • Modified radical hysterectomy and pelvic lymphadenectomy (with or without SLN mapping)

  • External pelvic radiation therapy with brachytherapy

Criteria for radiation therapy after radical hysterectomy

Criteria used to determine whether pelvic radiation with concurrent chemotherapy should be done after radical hysterectomy include the following (see table Sedlis Criteria for External Pelvic Radiation After Radical Hysterectomy Sedlis Criteria for External Pelvic Radiation After Radical Hysterectomy* Sedlis Criteria for External Pelvic Radiation After Radical Hysterectomy* ):

  • Presence of lymphovascular space invasion

  • Depth of invasion

  • Tumor size

Risk factors such as positive margins and/or pathologically confirmed positive pelvic lymph nodes and/or microscopic involvement of the parametrium are considered higher risk. In a randomized trial, the estimated 4-year survival rates for patients with stage IB cervical cancer and high-risk factors were 81% for those treated with combined chemotherapy and radiation therapy and 71% for those treated with radiation therapy alone (4 Treatment references Cervical cancer is usually a squamous cell carcinoma; less often, it is an adenocarcinoma. The cause of most cervical cancers is human papillomavirus infection. Cervical neoplasia is often asymptomatic... read more Treatment references , 5 Treatment references Cervical cancer is usually a squamous cell carcinoma; less often, it is an adenocarcinoma. The cause of most cervical cancers is human papillomavirus infection. Cervical neoplasia is often asymptomatic... read more Treatment references ).

Table

Stages IB1, IB2, and IIA1

For stages IB1, IB2, and IIA1, the standard recommendation is

  • Open radical hysterectomy with bilateral pelvic lymphadenectomy (with or without SLN mapping)

Radical hysterectomy includes resection of the uterus (including the cervix), parts of the cardinal and uterosacral ligaments, the upper 1 to 2 cm of the vagina, the pelvic lymph nodes and parametrium. The Querleu & Morrow classification system describes four types of radical hysterectomy based on the lateral extent of resection; a few subtypes take nerve preservation and paracervical lymphadenectomy into account (6 Treatment references Cervical cancer is usually a squamous cell carcinoma; less often, it is an adenocarcinoma. The cause of most cervical cancers is human papillomavirus infection. Cervical neoplasia is often asymptomatic... read more Treatment references ).

Results from a randomized trial (7 Treatment references Cervical cancer is usually a squamous cell carcinoma; less often, it is an adenocarcinoma. The cause of most cervical cancers is human papillomavirus infection. Cervical neoplasia is often asymptomatic... read more Treatment references ) showed that minimally invasive surgery (laparoscopy or robot-assisted laparoscopy) resulted in a lower overall survival rate and a higher recurrence rate than total abdominal radical hysterectomy. Therefore, open radical hysterectomy is recommended as the appropriate approach.

When patients are not considered ideal candidates for surgery because of comorbidities, another valid option is external pelvic radiation therapy and brachytherapy with or without concurrent platinum-based chemotherapy.

Another treatment option is radical hysterectomy and bilateral pelvic lymphadenectomy (with or without para-aortic lymphadenectomy), sometimes with adjuvant radiation therapy (see table Sedlis Criteria for External Pelvic Radiation After Radical Hysterectomy Sedlis Criteria for External Pelvic Radiation After Radical Hysterectomy* Sedlis Criteria for External Pelvic Radiation After Radical Hysterectomy* ).

If extracervical spread is noted during radical hysterectomy, the procedure should be aborted, and postoperative radiation therapy with concurrent chemotherapy is recommended to prevent local recurrence (8 Treatment references Cervical cancer is usually a squamous cell carcinoma; less often, it is an adenocarcinoma. The cause of most cervical cancers is human papillomavirus infection. Cervical neoplasia is often asymptomatic... read more Treatment references ).

Stages IB3, IIA2, IIB, III, and IVA

The standard therapy for stages IB3, IIA2, IIB, III, and IVA cancer is

  • External pelvic radiation therapy with brachytherapy and concurrent platinum-based chemotherapy

To determine the extent of the radiation field, clinicians may evaluate spread to para-aortic lymph nodes clinically (abdominal CT and/or MRI) or surgically (pelvic and para-aortic lymphadenectomy). In a randomized trial, oncologic outcomes did not differ significantly in patients with stage IIB through IVA staged clinically compared with those staged surgically before chemoradiation. In this study, laparoscopic staging appeared to be safe, did not delay primary treatment, and resulted in upstaging in 33% of patients with locally advanced cervical cancer (9 Treatment references Cervical cancer is usually a squamous cell carcinoma; less often, it is an adenocarcinoma. The cause of most cervical cancers is human papillomavirus infection. Cervical neoplasia is often asymptomatic... read more Treatment references ).

When cancer is limited to the cervix and/or pelvic lymph nodes, the standard recommendation is

  • External beam radiation therapy, followed by brachytherapy (local radioactive implants, usually using cesium) to the cervix

Radiation therapy may cause acute complications (eg, radiation proctitis and cystitis) and, occasionally, late complications (eg, vaginal stenosis, intestinal obstruction, rectovaginal and vesicovaginal fistula formation).

Chemotherapy (cisplatin or carboplatin) is usually given with radiation therapy, often to sensitize the tumor to radiation.

Although stage IVA cancers are usually treated with radiation therapy initially, pelvic exenteration (excision of all pelvic organs) may be considered. If after radiation therapy, cancer remains but is confined to the central pelvis, exenteration is indicated and cures up to 40% of patients. The procedure may include continent or incontinent urostomy, low anterior rectal anastomosis without colostomy or with an end-descending colostomy, omental carpet to close the pelvic floor (J-flap), and vaginal reconstruction with gracilis or rectus abdominis myocutaneous flaps.

Stage IVB and recurrent cancer

Chemotherapy is the primary treatment for stage IVB cervical cancer. Response rates are about 48%.

Adding bevacizumab to combination chemotherapy (cisplatin plus paclitaxel or topotecan plus paclitaxel) resulted in an improvement of 3.7 months in median overall survival in patients with recurrent, persistent, or metastatic cervical cancer (10 Treatment references Cervical cancer is usually a squamous cell carcinoma; less often, it is an adenocarcinoma. The cause of most cervical cancers is human papillomavirus infection. Cervical neoplasia is often asymptomatic... read more Treatment references ).

Metastases outside the radiation field appear to respond better to chemotherapy than does previously irradiated cancer or metastases in the pelvis.

Clinicians should consider testing for mismatch repair (MMR) and microsatellite instability (MSI), PD-L1 (programmed cell death-ligand 1) expression, and/or NTRK gene fusion if patients have recurrent, progressive, or metastatic cervical cancer. Results can help predict responses to immunotherapies such as PD-L1 inhibitors.

In a randomized, placebo-controlled trial, adding pembrolizumab to chemotherapy, improved progression-free and overall survival in patients with persistent, recurrent, or metastatic cervical cancer (11 Treatment references Cervical cancer is usually a squamous cell carcinoma; less often, it is an adenocarcinoma. The cause of most cervical cancers is human papillomavirus infection. Cervical neoplasia is often asymptomatic... read more Treatment references ).

Fertility-sparing surgery

In some patients who have early-stage cervical cancer (IA1 with LVSI, IA2, IB1, some cases of IB2) and who wish to preserve fertility, fertility-sparing surgery is an option.

Surgical treatment of cervical cancer does not include oophorectomy unless ovaries appear abnormal. In young patients having surgery, ovarian preservation is particular important to avoid premature menopause. Before pelvic radiation, ovaries may be moved outside the radiation field (oophoropexy) to avoid toxic exposure. Patients should be counseled about the benefit of preserving ovary function versus the risk of potential ovarian metastases. In a study of 3471 patients who had stage Ib through IIb cervical cancer treated with a radical hysterectomy, the cancer metastasized to the ovaries in 1.5% of patients (12 Treatment references Cervical cancer is usually a squamous cell carcinoma; less often, it is an adenocarcinoma. The cause of most cervical cancers is human papillomavirus infection. Cervical neoplasia is often asymptomatic... read more Treatment references ). Ovarian metastasis was more common among patients with adenocarcinoma (5.31%) than among those with squamous cell carcinoma (0.79%).

Surgical options for uterine conservation include

  • Radical trachelectomy with nodal evaluation

  • Cervical conization

Radical trachelectomy is removal of the cervix, parametria immediately adjacent to the cervix, upper 2 cm of the vagina, and pelvic lymph nodes. The uterus is conserved and is reattached to the upper vagina, preserving the potential for fertility. Candidates for this procedure are patients with the following:

  • Histologic subtypes such as squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma (not neuroendocrine or small cell carcinoma or sarcoma)

  • Stage IA1/grade 2 or 3 with lymphovascular space invasion

  • Stage IA2

  • Stage IB1

Invasion of the upper cervix and lower uterine segment should be excluded by MRI before surgery. Rates of recurrence and death are similar to those after radical hysterectomy. If patients who have this procedure plan to have children, delivery must be cesarean. After a radical trachelectomy, fertility rates range from 50 to 70%, and the recurrence rate is about 5 to 10%.

Radical trachelectomy can be performed via vaginal surgery, laparotomy, laparoscopy, or robotic-assisted surgery. There has been concern about the safety of radical trachelectomy using minimally invasive approaches (laparoscopy or robotic-assisted surgery) compared with laparotomy. In one retrospective study of patients with early-stage cervical cancer (≤ 2 cm), laparotomy compared with minimally invasive approaches had comparable 4.5-year disease-free survival rates (13 Treatment references Cervical cancer is usually a squamous cell carcinoma; less often, it is an adenocarcinoma. The cause of most cervical cancers is human papillomavirus infection. Cervical neoplasia is often asymptomatic... read more Treatment references ).

For patients with low-risk, early-stage cervical cancer, conization with pelvic nodal evaluation may be an alternative to radical trachelectomy. In a single-arm, prospective study, conservative surgery (cervical conization or simple hysterectomy with nodal evaluation) appeared to be safe and feasible in women with low-risk, early-stage cervical cancer; the 2-year recurrence rate was 3.5% (14 Treatment references Cervical cancer is usually a squamous cell carcinoma; less often, it is an adenocarcinoma. The cause of most cervical cancers is human papillomavirus infection. Cervical neoplasia is often asymptomatic... read more Treatment references ). Studies to determine the optimal treatment for patients with early-stage cervical cancer are ongoing.

An ongoing prospective study (CONTESSA) is evaluating the role of neoadjuvant chemotherapy followed by fertility-sparing surgery in patients who have tumors 2 to 4 cm and who wish to preserve fertility.

Treatment references

  • 1. National Comprehensive Cancer Network (NCCN): NCCN Clinical Practice Guidelines in Oncology: Cervical Cancer. Version 1.2022. October 26, 2021. Accessed 6/21/22.

  • 2. Sedlis A, Bundy BN, Rotman MZ, et al: A randomized trial of pelvic radiation therapy versus no further therapy in selected patients with stage IB carcinoma of the cervix after radical hysterectomy and pelvic lymphadenectomy: A Gynecologic Oncology Group Study. Gynecol Oncol 73 (2):177–183, 1999. doi: 10.1006/gyno.1999.5387

  • 3. Rotman M, Sedlis A, Piedmonte MR, et al: A phase III randomized trial of postoperative pelvic irradiation in stage IB cervical carcinoma with poor prognostic features: Follow-up of a Gynecologic Oncology Group Study. Int J Radiat Oncol Biol Phys 65 (1):169–176, 2006. doi: 10.1016/j.ijrobp.2005.10.019 Epub 2006 Jan 19.

  • 4. Peters WA, Liu PY, Barrett RJ, et al: Concurrent chemotherapy and pelvic radiation therapy compared with pelvic radiation therapy alone as adjuvant therapy after radical surgery in high-risk early-stage cancer of the cervix. J Clin Oncol 18 (8):1606–1613, 2000. doi: 10.1200/JCO.2000.18.8.1606

  • 5. Monk BJ, Wang J, Im S, et al: Rethinking the use of radiation and chemotherapy after radical hysterectomy: a clinical-pathologic analysis of a Gynecologic Oncology Group/Southwest Oncology Group/Radiation Therapy Oncology Group trial. Gynecol Oncol 96 (3):721–728, 2005. doi: 10.1016/j.ygyno.2004.11.007

  • 6. Querleu D, Morrow CP: Classification of radical hysterectomy. Lancet Oncol 9 (3):297–303, 2008. doi: 10.1016/S1470-2045(08)70074-3

  • 7. Ramirez PT, Frumovitz M, Pareja R, et al: Minimally invasive versus abdominal radical hysterectomy for cervical cancer. N Engl J Med 379 (20): 1895–1904, 2018. doi: 10.1056/NEJMoa1806395

  • 8. Cibula D, Dostalek L, Hillemanns P, et al: Completion of radical hysterectomy does not improve survival of patients with cervical cancer and intraoperatively detected lymph node involvement: ABRAX international retrospective cohort study. Eur J Cancer 143:88–100, 2021. doi: 10.1016/j.ejca.2020.10.037 Epub 2020 Dec 5.

  • 9. Marnitz S, Tsunoda AT, Martus P, et al: Surgical versus clinical staging prior to primary chemoradiation in patients with cervical cancer FIGO stages IIB–IVA: Oncologic results of a prospective randomized international multicenter (Uterus-11) intergroup study. Int J Gynecol Cancer 30:1855–1861, 2020. doi:10.1136/ijgc-2020-001973

  • 10. Tewari KS, Sill MW, Long HJ III: Improved survival with bevacizumab in advanced cervical cancer. N Engl J Med 370 (8):734-743, 2014. doi: 10.1056/NEJMoa1309748

  • 11. Colombo N, Dubot C, Lorusso D, et al; Pembrolizumab for persistent, recurrent, or metastatic cervical cancer. N Engl J Med 385 (20):1856–1867, 2021. doi: 10.1056/NEJMoa2112435 Epub 2021 Sep 18.

  • 12. Shimada M, Kigawa J, Nishimura R, Yamaguchi S, et al: Ovarian metastasis in carcinoma of the uterine cervix. Gynecol Oncol 101 (2):234–237, 2006. doi: 10.1016/j.ygyno.2005.10.004 Epub 2005/11/23.

  • 13. Salvo G, Ramirez PT, Leitao M, et al: Open vs minimally invasive radical trachelectomy in early-stage cervical cancer: International Radical Trachelectomy Assessment Study. Am J Obstet Gynecol 226 (1):97.e1-97.e16, 2022. doi: 10.1016/j.ajog.2021.08.029 Epub 2021 Aug 27.

  • 14. Schmeler KM, Pareja R, Aldo Lopez Blanco AL, et al: ConCerv: A prospective trial of conservative surgery for low-risk early-stage cervical cancer. Int J Gynecol Cancer 31 (10):1317–1325, 2021. doi: 10.1136/ijgc-2021-002921 Epub 2021 Sep 7.

Prevention of Cervical Cancer

Screening tests

Routine cervical cancer screening effectively detects preinvasive and early-stage disease and decreases cervical cancer incidence and mortality rates.

Two types of screening tests for cervical abnormalities are used:

  • Tests for high-risk HPV genotypes

  • Pap test (cervical cytology)

If Pap and HPV tests are not available (eg, in resource-limited settings), visual inspection of the cervix after application of acetic acid or Lugol iodine is an alternative screening method.

  • Screening should begin at age 25, rather than age 21.

  • If primary human papillomavirus (HPV) testing is available, it should be started at age 25 years, rather than at age 30 and done every 5 years; cytology (eg, Pap tests) is not needed.

  • If primary HPV testing is not available, co-testing with Pap and HPV tests should be done every 5 years or a Pap test should be done every 3 years.

  • For those over age 65, guidance remains the same: Testing is stopped if an adequate series of previous tests have been normal during the preceding 10 years; testing should be continued if women have not had adequate normal test results or started if they have not been screened previously.

If women have had a hysterectomy for a disorder other than cancer and have not had abnormal Pap test results, screening is not indicated.

Table

HPV testing is the preferred method of follow-up evaluation for all women with ASCUS (atypical squamous cells of undetermined significance), an inconclusive finding detected by Pap tests. If HPV testing shows that the woman does not have HPV, screening should continue at the routinely scheduled intervals. If HPV is present, colposcopy should be done.

HPV vaccine

  • A bivalent vaccine that protects against subtypes 16 and 18 (which cause most cervical cancers)

  • A quadrivalent vaccine that protects against subtypes 16 and 18 plus 6 and 11

  • A 9-valent vaccine that protects against the same subtypes as the quadrivalent plus subtypes 31, 33, 45, 52, and 58 (which cause about 15% of cervical cancers)

The vaccines aim to prevent cervical cancer but do not treat it. All three vaccines are most effective if given before first sexual activity and potential exposure to HPV.

The HPV vaccine is recommended for all people, ideally before they become sexually active. The standard recommendation is to vaccinate beginning at age 11 to 12 years, but vaccination may begin at age 9.

Prevention reference

  • 1. Fontham ETH, Wolf AMD, Church TR, et al: Cervical cancer screening for individuals at average risk: 2020 guideline update from the American Cancer Society. CA Cancer J Clin 70 (5):321–346, 2020. doi: 10.3322/caac.21628 Epub 2020 Jul 30.

Key Points

  • Consider cervical cancer if women have abnormal cervical cancer screening (HPV or Pap test) results, visible cervical lesions, or abnormal, particularly postcoital, vaginal bleeding.

  • Do a colposcopy and/or biopsy to further evaluate and confirm the diagnosis.

  • Stage cervical cancer clinically, using biopsy, pelvic examination, and available imaging, including chest x-ray; also use ultrasonography, PET/CT, MRI, or CT and surgical pathology, if available.

  • Treatment is surgical resection for early-stage cancer, radiation therapy plus chemotherapy for locally advanced cancer, and chemotherapy for metastatic and recurrent cancer.

  • Recommend HPV vaccination for children before first sexual activity.

More Information

The following is an English-language resource that may be useful. Please note that THE MANUAL is not responsible for the content of this resource.

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