Sections

Cervical Cancer

Archetype D 60 regimens (Main Regimens) cervical

Squamous cell carcinoma, adenocarcinoma, and adenosquamous

DefinitionClick to collapse

Cervical cancer refers to malignant neoplasms arising from the uterine cervix, a fibromuscular organ located at the lower end of the uterus, connecting the uterine cavity to the vaginal canal. The cervix is divided into two main regions: the ectocervix (visible portion protruding into the vagina, lined by non-keratinizing squamous epithelium) and the endocervix (inner canal, lined by mucus-secreting glandular epithelium). The transformation zone, the junction between these two epithelial types, is the critical anatomical site where most cervical cancers originate, as this region undergoes continuous metaplastic changes and is particularly susceptible to human papillomavirus (HPV) infection and neoplastic transformation [1-4]. Cervical cancer is a histologically heterogeneous disease. The NCCN Guidelines for Cervical Cancer include the management of squamous cell carcinoma, adenosquamous carcinoma, adenocarcinoma of the cervix, and small cell neuroendocrine carcinoma of the cervix [MS-3]. Squamous cell carcinoma (SCC) is the most common histologic type, accounting for approximately 80% to 90% of all cervical carcinomas worldwide [MS-2]. Adenocarcinoma accounts for approximately 20% of all cervical cancers, and adenocarcinoma and adenosquamous carcinoma (ASC) together make up the remaining proportion [MS-2]. ASC is rare, accounting for approximately 5% to 6% of all cervical carcinomas [MS-17]. Small cell neuroendocrine carcinoma (NECC) accounts for approximately 1% to 1.5% of all cervical cancers and, while rare, the cervix is the most common site for neuroendocrine carcinoma (including small cell and large cell neuroendocrine carcinoma) in the female genital tract [MS-40]. Glassy-cell carcinomas, sarcomas, and other histologic types are not within the scope of the NCCN Guidelines [MS-3]. The earliest stages of cervical carcinoma may be asymptomatic or associated with watery vaginal discharge, postcoital bleeding, or intermittent spotting [MS-3]. Because of the accessibility of the uterine cervix, cervical cytology (Papanicolaou or Pap tests) and cervical biopsies can usually result in an accurate diagnosis [MS-3]. The revised 2018 FIGO staging system stratifies cervical cancer from stage I (confined to the cervix) through stage IV (extending beyond the true pelvis or involving the mucosa of the bladder or rectum), with further subdivisions based on depth of invasion, tumor size, and nodal involvement [ST-1].

EpidemiologyClick to collapse

An estimated 13,360 new cases of carcinoma of the uterine cervix will be diagnosed in the United States in 2025 [MS-2]. Globally in 2022, there were an estimated 661,021 cervical cancer cases [MS-2]. It is the fourth most common cancer in females worldwide, with 85% of cases occurring in developing countries [MS-2]. It is the most diagnosed cancer in 23 countries and the leading cause of cancer death in 36 countries [MS-2]. Squamous cell carcinoma (SCC) accounts for approximately 80% and adenocarcinoma accounts for approximately 20% of all cervical cancers [MS-2]. The ASC subtype accounts for approximately 5% to 6% of all cervical carcinomas [MS-2]. Small cell NECC accounts for approximately 1% to 1.5% of all cervical cancers [MS-40]. Incidence rates of cervical SCC are highest in Black and Hispanic individuals assigned female at birth, while incidence rates of cervical adenocarcinoma are highest among Hispanic and white individuals assigned female at birth [MS-2]. AC/ASC of the cervix have increased over the past 3 decades [MS-2].
Annual Incidence
An estimated 4,320 people are estimated to die of cervical cancer in the United States in 2025 [MS-2]. Globally in 2022, there were 348,189 deaths associated with cervical cancer [MS-2]. Effective treatment for cervical cancer (including surgery and concurrent chemoradiation) can yield cures in 80% of patients with early-stage disease (stages I–II) and in 60% of patients with stage III disease [MS-44].
Annual Mortality
Cervical cancer rates are decreasing in the United States following the introduction of screening [MS-2]. However, incidence remains high among Hispanic/Latino, Black, and Asian populations [MS-2]. In developed countries, the substantial decline in incidence and mortality of SCC of the cervix is presumed to be the result of effective screening and higher HPV-vaccination coverage, although racial, ethnic, and geographic disparities exist [MS-2]. AC/ASC of the cervix have increased over the past 3 decades, probably because cervical cytologic screening methods are less effective for AC/ASC [MS-2].
Trend & Projections
Incidence rates of cervical SCC are highest in Black and Hispanic individuals assigned female at birth, while incidence rates of cervical adenocarcinoma are highest among Hispanic and white individuals assigned female at birth [MS-2]. The substantial decline in incidence and mortality of SCC of the cervix exists alongside racial, ethnic, and geographic disparities [MS-2]. Small cell NECC presents predominantly in younger women (mean age 30–40 years) and is aggressive with rapid metastasis [MS-40].
Demographics

SubtypesClick to collapse

80%–90% of all cervical carcinomas; >90% of SCCs are HPV-associated [CERV-A 2 of 7, MS-2]
Squamous Cell Carcinoma (SCC) — HPV-Associated

Cervical squamous cell carcinoma is a squamous epithelial tumor with stromal invasion and/or exophytic invasion. It accounts for approximately 80% to 90% of cervical carcinomas worldwide. The majority of cervical SCCs (>90%) are HPV-associated, with high-risk HPV 16 and 18 being the most common types. Histologic patterns include keratinizing (presence of keratin pearls), non-keratinizing, basaloid (nests of basal-type squamous cells), warty (condylomatous), and papillary types. Non-keratinizing and basaloid patterns are most commonly noted with HPV-associated tumors. Almost all HPV-associated SCCs show strong and diffuse p16 overexpression in nuclei and cytoplasm by immunohistochemistry (IHC).

5%–7% of cervical SCCs [CERV-A 2 of 7]
Squamous Cell Carcinoma (SCC) — HPV-Independent

HPV-independent cervical SCC is a relatively recently described entity, with 5%–7% of cervical SCCs reported to be HPV-negative. These tumors typically present later in life (7th decade) and at an advanced stage. HPV-independent cervical SCCs have been described to demonstrate TP53, KRAS, ARID1A, and PTEN mutations. Morphologically, HPV-independent SCCs are usually of the keratinizing type. Morphology alone is unreliable for determining HPV association, and utility of p16 IHC and/or molecular HPV typing is recommended for establishing HPV status [CERV-A 2 of 7].

Approximately 75% of HPV-associated adenocarcinomas; adenocarcinomas as a group account for ~20% of all cervical cancers [CERV-A 4 of 7, MS-2]
Endocervical Adenocarcinoma — HPV-Associated (Usual Type)

Endocervical adenocarcinoma is a gland-forming tumor typically originating in the transformation zone, demonstrating stromal invasion and/or expansile type invasion. Adenocarcinomas of the cervix can be HPV-associated (high-risk HPV types 18, 16, and 45 most commonly) or HPV-independent. The usual type accounts for approximately 75% of HPV-associated cases and includes villoglandular and micropapillary subtypes. Mucinous types include intestinal, signet-ring cell, and invasive stratified mucin-producing carcinoma (ISMC). 95% of HPV-associated carcinomas will demonstrate block-type p16 expression by IHC. The Silva classification system is used for evaluating patterns of invasion in HPV-associated endocervical adenocarcinoma, subdividing these tumors into three categories (A, B, C) with Pattern A tumors having excellent survival and no lymph node metastases or recurrences [CERV-A 3 of 7, CERV-A 4 of 7, MS-10, MS-11].

10%–15% of cervical adenocarcinomas (up to 25% in Japan) [CERV-A 4 of 7]
Endocervical Adenocarcinoma — HPV-Independent (Gastric Type)

Gastric-type adenocarcinoma makes up approximately 10%–15% of cervical adenocarcinomas (with up to 25% noted in Japan). It is found in association with Peutz-Jeghers syndrome (STK11 mutation), and while typically negative for p16 block expression, it may show aberrant p53 expression in approximately 50% of cases. These tumors show a high prevalence of invasion, extrauterine spread, and present at an advanced stage. They are considered inappropriate for fertility-sparing surgery due to their diagnostic challenges and potentially aggressive nature [CERV-A 4 of 7, MS-17].

3% of endocervical adenocarcinomas [CERV-A 4 of 7]
Endocervical Adenocarcinoma — HPV-Independent (Clear Cell)

Clear cell carcinomas make up 3% of endocervical adenocarcinomas, occurring sporadically or in association with in-utero diethylstilbestrol (DES) exposure. These tumors may demonstrate diffuse p16 expression despite the absence of HPV infection. In these instances, high-risk HPV in situ hybridization (ISH) can be utilized to confirm HPV status [CERV-A 4 of 7, MS-17].

Rare subtype of endocervical adenocarcinoma [CERV-A 4 of 7]
Endocervical Adenocarcinoma — HPV-Independent (Mesonephric)

Mesonephric type demonstrates mesonephric (Wolffian) differentiation and is associated with mesonephric remnants. It typically is located deep in the lateral wall and histologically demonstrates architectural crowding, haphazard infiltration, atypia, mitotic activity, and necrosis. GATA-3 and CD10 IHC stains will be positive in the tumor and associated mesonephric remnants [CERV-A 4 of 7].

~1% of primary endocervical adenocarcinomas [CERV-A 4 of 7]
Endocervical Adenocarcinoma — HPV-Independent (Endometrioid)

Endometrioid carcinoma is quite uncommon, approximating 1% of primary endocervical adenocarcinomas, and may present in the setting of endometriosis; however, a primary endometrial carcinoma must be ruled out. Utilizing a panel of IHC stains (vimentin, estrogen receptor [ER], p16, and monoclonal carcinoembryonic antigen [CEA]) may be helpful in differentiating between endocervical and endometrial carcinoma. Typically, endometrioid adenocarcinoma will express vimentin and ER, while endocervical adenocarcinoma is positive for monoclonal CEA and p16 (when HPV-associated) [CERV-A 4 of 7, MS-17].

Approximately 5%–6% of all cervical carcinomas [CERV-A 5 of 7, MS-2]
Adenosquamous Carcinoma (ASC)

Epithelial tumor with malignant squamous and malignant glandular differentiation. The tumor components (squamous and glandular) should be admixed and be able to be discerned on routine histology. The squamous component typically demonstrates abundant glycogen-rich (clear) cytoplasm, while the gland-forming component is often of usual HPV-associated adenocarcinoma. IHC for p16 usually shows overexpression in both components. Additional IHC stains such as CK7, CEA, and PAX8 may be utilized to highlight the glandular component, while p63 and p40 highlight the squamous component. Clinical outcomes are similar to cervical adenocarcinoma [CERV-A 5 of 7, MS-17].

<5% of cervical cancers; accounts for approximately 1%–1.5% of all cervical cancers [CERV-A 6 of 7, MS-40]
Small Cell Neuroendocrine Carcinoma (NECC)

Although rare, comprising <5% of cervical cancers, the cervix is the most common site for neuroendocrine carcinoma (eg, small cell and large cell neuroendocrine carcinoma) in the genital tract. NECC is clinically aggressive, with rapid metastasis and a frequently poor clinical outcome. NECC is usually HPV-associated; types 16 and 18 are the most common (18 more often than 16). This carcinoma type morphologically resembles neuroendocrine carcinomas of the lung. Small cell NECC is a morphologic diagnosis. The predominant growth pattern is diffuse, with additional patterns including insular, perivascular, and thick trabeculae with serpiginous growth. Cytologic features include a uniform population of cells with indistinct cell borders, scant cytoplasm, and hyperchromatic nuclei with fine granular chromatin. Small cell NECC is variably positive for chromogranin, CD56, and synaptophysin by IHC. CD56 and synaptophysin are the most sensitive neuroendocrine markers, but CD56 lacks specificity. Chromogranin is the most specific neuroendocrine marker, but lacks sensitivity with only about 50%–60% of small cell NECC being positive. Insulinoma-associated protein 1 (INSM1) and synaptophysin are other neuroendocrine markers, with 80% and 70% positivity, respectively. A high percentage of primary NECCs are thyroid transcription factor-1 (TTF-1)-positive, and this marker is of no value in distinction from a pulmonary metastasis [CERV-A 6 of 7, MS-40].

Molecular PathogenesisClick to collapse

The development of cervical cancer is overwhelmingly driven by persistent infection with high-risk human papillomavirus (HPV), which is the most important factor in the development of cervical cancer [MS-2]. The incidence of cervical cancer appears to be related to the prevalence of HPV in the population; in countries with high incidence of cervical cancer, the prevalence of chronic HPV is approximately 10% to 20%, whereas the prevalence in low-incidence countries is 5% to 10% [MS-2]. The majority of cervical SCCs (>90%) are HPV-associated, with high-risk HPV 16 and 18 being the most common types [CERV-A 2 of 7]. Adenocarcinomas of the cervix can also be HPV-associated, with high-risk HPV types 18, 16, and 45 most commonly involved [CERV-A 3 of 7]. Adenosquamous carcinoma accounts for approximately 5% to 6% of all cervical carcinomas, and HPV-associated adenocarcinomas demonstrate block-type p16 expression by IHC in 95% of cases [CERV-A 4 of 7, CERV-A 5 of 7]. Small cell NECC is usually HPV-associated; types 16 and 18 are the most common (18 more often than 16) [CERV-A 6 of 7]. Around 5% of cervical tumors are reported as HPV-independent tumors [MS-2]. HPV-independent cervical SCC, described as a relatively recently entities, have been described to demonstrate TP53, KRAS, ARID1A, and PTEN mutations [CERV-A 2 of 7]. In 2020, the World Health Organization updated the Female Genital Tumors classification of cervical cancer by subdividing the cervical cancer lesions into HPV-associated and HPV-independent tumors based on the new pathological findings [MS-2]. For molecular profiling, the NCCN Panel recommends comprehensive molecular profiling by an FDA-approved assay, or a validated test performed in a CLIA-certified laboratory including at least HER2, mismatch repair (MMR)/microsatellite instability (MSI), tumor mutational burden (TMB) testing, NTRK, and RET for predicting rare pan-tumor targeted therapy opportunities in the setting of metastatic or recurrent disease [CERV-A 1 of 7]. Cervical carcinomas demonstrating HER2 amplification/overexpression have been associated with higher recurrence rates and worse prognosis [CERV-A 1 of 7]. HER2 positivity rate in cervical cancer is approximately 2% to 6% [MS-34]. The HER2-positive rate of HER2 IHC 3+ or 2+ in cervical cancer can be found [MS-34]. The most common HER2 variant in cervical cancer is S310F/Y mutation [MS-16]. NTRK gene fusions are found in about 1% of all solid tumors [MS-15]. RET gene fusions most commonly occur in thyroid and non-small cell lung cancers and are observed in <1% of patients with other solid tumors [MS-16]. TMB testing has shown that cervical cancer had the highest proportion of patients with TMB-high status (21%) in the KEYNOTE-158 study [MS-14]. PD-L1 combined positive score (CPS) testing is recommended for patients with recurrent, progressive, or metastatic disease to guide treatment selection [CERV-A 1 of 7, MS-13]. HPV-independent endocervical adenocarcinomas, including gastric type (10%–15% of cervical adenocarcinomas, associated with Peutz-Jeghers syndrome and STK11 mutation), clear cell (3% of endocervical adenocarcinomas, associated with DES exposure), mesonephric, and endometrioid types, have less favorable prognosis compared to HPV-associated tumors [CERV-A 4 of 7, MS-17].

Risk FactorsClick to collapse

Persistent HPV infection

Persistent HPV infection is the most important factor in the development of cervical cancer. High-risk HPV types 16 and 18 are most commonly implicated, found in the majority of HPV-associated cervical SCCs. In countries with a high incidence of cervical cancer, the prevalence of chronic HPV is approximately 10% to 20%, whereas in low-incidence countries it is 5% to 10%.

Smoking

A history of smoking is an epidemiologic risk factor associated with cervical cancer. Smoking cessation should be advised in current smokers, and former smokers should continue to avoid smoking.

Oral contraceptive use

Oral contraceptive use has been identified as an epidemiologic risk factor associated with cervical cancer.

Early age of onset of coitus

Early age of onset of sexual intercourse is an epidemiologic risk factor associated with cervical cancer.

Larger number of sexual partners

A larger number of sexual partners is an epidemiologic risk factor associated with cervical cancer.

History of sexually transmitted disease

A history of sexually transmitted disease is an epidemiologic risk factor associated with cervical cancer.

Certain autoimmune diseases

Certain autoimmune diseases have been identified as epidemiologic risk factors associated with cervical cancer.

Chronic immunosuppression

Chronic immunosuppression, including HIV infection, is an epidemiologic risk factor associated with cervical cancer. The guidelines recommend considering HIV testing, especially in younger patients. Patients with cervical cancer and HIV should be referred to an HIV specialist and should be treated for cervical cancer as per the guidelines without modification solely on the basis of HIV status.

Clinical FeaturesClick to collapse

Typical Presentation

Cervical cancer may present in early stages as asymptomatic or with subtle symptoms such as watery vaginal discharge, postcoital bleeding, or intermittent spotting, which are often not recognized by the patient. As the disease advances, symptoms can include pelvic pain, leg edema, weight loss, anorexia, and persistent coughing. On examination, a visible or palpable cervical mass, ulceration, or barrel-shaped cervix may be noted. For advanced stages, involvement of adjacent organs (e.g., bladder, rectum) can cause hematuria, dysuria, rectal bleeding, or constipation.

Symptoms

Vaginal bleeding

Postcoital, intermenstrual, or postmenopausal bleeding

Vaginal discharge

Watery, foul-smelling, or bloody discharge

Pelvic pain

Dull, aching pain in the pelvis, lower back, or legs

Weight loss

Unintentional weight loss

Anorexia

Loss of appetite

Urinary symptoms

Dysuria, hematuria, frequency, or urgency

Rectal symptoms

Rectal bleeding, tenesmus, or constipation

Leg edema

Unilateral or bilateral swelling due to lymphatic or venous obstruction

Persistent cough

May indicate pulmonary metastases

Signs

Cervical mass or ulcer

Visible or palpable lesion on pelvic examination

Barrel-shaped cervix

Enlarged, firm cervix suggesting deep stromal invasion

Parametrial induration

Fixation or thickening of the parametria on bimanual exam

Pelvic sidewall mass

Fixed mass extending to the pelvic wall

Lymphadenopathy

Palpable inguinal or supraclavicular nodes

Red FlagsClick to collapse

InvestigationsClick to collapse

Diagnostic

Cervical biopsy

Gold standard for diagnosis of cervical cancer; obtains tissue for histologic subtype and grade.

Cone biopsy (cold knife conization preferred, LEEP acceptable)

Required to assess depth of invasion, margin status, and lymphovascular space invasion (LVSI) for staging and treatment planning.

Endocervical curettage (ECC)

Evaluates endocervical canal for invasion, especially when adenocarcinoma in situ vs. invasive adenocarcinoma is suspected.

Staging

Pelvic MRI (with and without contrast)

Preferred imaging for assessing local tumor extent, parametrial invasion, vaginal involvement, and lymph node status.

FDG-PET/CT (neck/chest/abdomen/pelvis/groin)

Preferred for evaluating metastatic disease (lymph nodes, distant metastases) in stages IB1–IVA.

Chest/abdomen/pelvis CT with contrast

Alternative to PET/CT for metastatic evaluation; useful for assessing lymph nodes and distant organs.

Transvaginal ultrasound

May be used if MRI is contraindicated to assess local tumor extent.

Brain MRI

For small cell neuroendocrine carcinoma (NECC) to evaluate for brain metastases.

Cystoscopy/proctoscopy

To evaluate bladder or rectal invasion when symptoms or clinical findings suggest involvement (e.g., barrel-shaped lesion, anterior vaginal involvement).

Examination under anesthesia (EUA)

Allows thorough pelvic assessment for parametrial and vaginal involvement.

Biomarkers

PD-L1 (combined positive score, CPS)

Predicts response to pembrolizumab in recurrent/metastatic disease.

HPV testing (in situ hybridization or molecular testing) or p16 IHC

Determines HPV association; HPV-associated tumors have better prognosis and may guide treatment.

HER2 IHC (with reflex to FISH if equivocal)

Identifies HER2 amplification/overexpression, which is associated with worse prognosis and potential targeted therapy (e.g., fam-trastuzumab deruxtecan).

Mismatch repair (MMR) / microsatellite instability (MSI)

dMMR/MSI-H tumors may respond to pembrolizumab.

Tumor mutational burden (TMB)

TMB-high tumors (≥10 mut/Mb) may respond to pembrolizumab.

NTRK gene fusion testing

Identifies tumors with NTRK fusions, which are sensitive to TRK inhibitors (larotrectinib, entrectinib, repotrectinib).

RET gene fusion testing

Identifies tumors with RET fusions, which are sensitive to selpercatinib.

StagingClick to collapse

FIGO 2018 staging system (International Federation of Gynecology and Obstetrics)

T Categories

StageDescription
IAInvasive carcinoma diagnosed only by microscopy, maximum depth of invasion ≤5 mm.
IA1Measured stromal invasion ≤3 mm in depth.
IA2Measured stromal invasion >3 mm and ≤5 mm in depth.
IBInvasive carcinoma with deepest invasion >5 mm, limited to the cervix, size measured by maximum tumor diameter.
IB1Invasive carcinoma >5 mm depth of stromal invasion and ≤2 cm in greatest dimension.
IB2Invasive carcinoma >2 cm and ≤4 cm in greatest dimension.
IB3Invasive carcinoma >4 cm in greatest dimension.
IICervical carcinoma invades beyond the uterus but not to the lower third of the vagina or to the pelvic wall.
IIAInvolvement limited to the upper two-thirds of the vagina without parametrial invasion.
IIA1Invasive carcinoma ≤4 cm in greatest dimension.
IIA2Invasive carcinoma >4 cm in greatest dimension.
IIBWith parametrial invasion but not up to the pelvic wall.
IIICarcinoma involves the lower third of the vagina and/or extends to the pelvic wall and/or causes hydronephrosis or non-functioning kidney and/or involves pelvic and/or para-aortic lymph nodes.
IIIACarcinoma involves lower third of the vagina, with no extension to the pelvic wall.
IIIBExtension to the pelvic wall and/or hydronephrosis or non-functioning kidney (unless known to be due to another cause).
IIICInvolvement of pelvic and/or para-aortic lymph nodes (including micrometastases), irrespective of tumor size and extent.
IIIC1Pelvic lymph node metastasis only.
IIIC2Paraaortic lymph node metastasis.
IVCarcinoma has extended beyond the true pelvis or has involved (biopsy proven) the mucosa of the bladder or rectum.
IVASpread of the growth to adjacent organs.
IVBSpread to distant organs.

N Categories

StageDescription
N0No regional lymph node metastasis.
N1Regional lymph node metastasis (pelvic and/or para-aortic).

M Categories

StageDescription
M0No distant metastasis.
M1Distant metastasis (including peritoneal dissemination, distant lymph nodes, visceral metastases).

Stage Groupings

GroupCriteriaClinical MeaningFive Yr SurvivalTreatment Intent
IAT1a N0 M0Microinvasive disease; very low risk of lymph node metastasis (<1%).NoneCurative with fertility-sparing or non-fertility-sparing surgery.
IB1T1b1 N0 M0Invasive carcinoma ≤2 cm, confined to cervix; low to intermediate risk.NoneCurative with surgery or radiation.
IB2T1b2 N0 M0Invasive carcinoma 2-4 cm, confined to cervix; intermediate risk.NoneCurative with surgery or radiation.
IB3T1b3 N0 M0Invasive carcinoma >4 cm, confined to cervix; high risk.NoneCurative with chemoradiation.
IIA1T2a1 N0 M0Upper vaginal involvement, no parametrial invasion, tumor ≤4 cm.NoneCurative with surgery or radiation.
IIA2T2a2 N0 M0Upper vaginal involvement, no parametrial invasion, tumor >4 cm.NoneCurative with chemoradiation.
IIBT2b N0 M0Parametrial invasion but not to pelvic wall.NoneCurative with chemoradiation.
IIIAT3a N0 M0Lower third vaginal involvement, no extension to pelvic wall.NoneCurative with chemoradiation.
IIIBT3b N0 M0 or T任何 N0 M0 with hydronephrosisExtension to pelvic wall and/or hydronephrosis.NoneCurative with chemoradiation.
IIIC1T任何 N1 M0 (pelvic nodes only)Pelvic lymph node metastasis.NoneCurative with chemoradiation ± extended-field radiation.
IIIC2T任何 N1 M0 (paraaortic nodes)Paraaortic lymph node metastasis.NoneCurative with chemoradiation + extended-field radiation.
IVAT4 任何 N M0Spread to adjacent organs (bladder or rectum mucosa).NoneCurative intent with chemoradiation; pelvic exenteration may be considered.
IVB任何 T 任何 N M1Distant metastasis.NonePalliative; systemic therapy ± local radiation.

Staging Pearls

  • Staging is clinical based on FIGO 2018, but imaging (r) and pathology (p) findings can supplement staging, especially for lymph node status (stage IIIC).
  • Lymphovascular space invasion (LVSI) does not alter the FIGO stage but is an important prognostic factor for adjuvant treatment decisions.
  • For small cell neuroendocrine carcinoma (NECC), the same FIGO staging system is used, but the tumor is highly aggressive with frequent early metastasis.
  • In adenocarcinomas, the Silva pattern of invasion may provide additional prognostic information beyond depth of invasion.
  • Isolated tumor cells in lymph nodes do not change the stage but should be recorded.

Management PrinciplesClick to collapse

The primary goal of cervical cancer treatment is curative intent, achieved through a multidisciplinary approach tailored to disease stage, histology (squamous cell carcinoma, adenocarcinoma, adenosquamous carcinoma), and patient factors. Treatment philosophy is guided by the 2018 FIGO staging system and involves a risk-stratified strategy. For early-stage disease, the primary modality is surgery, often with fertility-sparing options considered for select patients. For locally advanced disease (stages IB3-IVA), definitive concurrent chemoradiation is the standard of care. For recurrent or metastatic disease, systemic therapy incorporating targeted agents and immunotherapy is central. Management of the rare small cell neuroendocrine carcinoma (NECC) of the cervix is modeled after regimens for small cell lung cancer. The NCCN emphasizes the importance of clinical trials and shared decision-making [1].

Curative

Patients with localized or locoregional disease (FIGO stages IA-IVA without distant metastases).

Treatment is directed at eliminating all detectable disease. Primary options include surgery (cone biopsy, trachelectomy, hysterectomy) for early stages, and definitive chemoradiation for locally advanced stages. Adjuvant therapy (radiation or chemoradiation) may be added postoperatively based on pathologic risk factors.

Palliative

Patients with recurrent, persistent, or metastatic disease not amenable to curative therapy (e.g., Stage IVB, distant metastases).

Treatment aims to control symptoms, prolong survival, and improve quality of life. Primary modalities include systemic therapy (chemotherapy, immunotherapy, targeted agents). Local therapies (e.g., radiation, ablative procedures) may be used for symptom control or oligometastatic disease [1].

Management requires a multidisciplinary team (MDT) including gynecologic oncologists, radiation oncologists, medical oncologists, pathologists, radiologists, and fertility specialists (REI). The NCCN panel is composed of experts from these disciplines. Complex cases, such as fertility preservation or pelvic exenteration for recurrence, should be managed at specialized centers [1].

Mdt Requirements

While not explicitly detailed with ECOG/PS cutoffs in this excerpt, the guideline implies that treatment intensity is tailored to patient fitness. For example, concurrent chemoradiation is standard for advanced disease but requires adequate organ function. Surgical candidacy is assessed medically. Systemic therapy options, including intensive combination regimens, are generally considered for patients with good performance status. Supportive care and best supportive care are options for those not tolerating active therapy [1].

Performance Status Guide

Management PathwaysClick to collapse

Stage IA1, No LVSI - Fertility Sparing

Branching: Fertility desire, Margin status after cone biopsy, Medical operability

Stage IA1 (no LVSI) on cone biopsy with negative margins (preferred non-fragmented specimen with at least 1-mm margins); patient desires fertility preservation.
Observe (Preferred); Cone biopsy (CKC preferred, LEEP acceptable) + SLN mapping or pelvic lymphadenectomy (Preferred)
Stage IA1, No LVSI - Non-Fertility Sparing

Branching: Margin status after cone biopsy, Medical operability

Stage IA1 (no LVSI) on cone biopsy. Negative margins and medically inoperable.
Observe (Preferred)
Negative margins and medically operable.
Type A hysterectomy (Preferred)
Positive margins for carcinoma and medically inoperable.
Repeat cone biopsy (preferred) or Brachytherapy ± pelvic EBRT (Preferred)
Positive margins for dysplasia or carcinoma and medically operable.
Consider repeat cone biopsy; or Type A hysterectomy (if margins positive for dysplasia) + SLN mapping or pelvic lymphadenectomy; or Type B radical hysterectomy (if margins positive for carcinoma) + SLN mapping or pelvic lymphadenectomy (Preferred)
Proceed to adjuvant treatment assessment based on surgical findings (CERV-6).
Stage IA1, With LVSI

Branching: Fertility desire, Margin status after cone/LEEP, Specimen integrity

Stage IA1 with LVSI based on cone/LEEP. Patient desires fertility preservation.
Cone biopsy (with negative margins) + pelvic SLN mapping/lymphadenectomy (Preferred)
Stage IA1 with LVSI, negative margins (or when specimen integrity unknown). Non-fertility sparing.
Type A hysterectomy + SLN mapping or pelvic lymphadenectomy (Preferred); Pelvic EBRT ± brachytherapy ± concurrent platinum-containing chemotherapy (Other recommended)
For surgical pathway, proceed to adjuvant treatment assessment based on findings (CERV-6).
Stage IA1 with LVSI, positive margins for dysplasia or carcinoma. Non-fertility sparing.
Consider repeat cone biopsy; or Type A hysterectomy (if margins positive for dysplasia) + SLN mapping or pelvic lymphadenectomy; or Type B radical hysterectomy (if margins positive for carcinoma) + SLN mapping or pelvic lymphadenectomy (Preferred)
Proceed to adjuvant treatment assessment based on surgical findings (CERV-6).
Stage IA2-IB1, Fertility Sparing

Branching: Conservative surgery criteria met, Tumor size, Histology, LVSI, Margins, Imaging

Stage IA2-IB1 based on cone biopsy; all conservative surgery criteria must be met: No LVSI (preferred), negative cone margins for cancer (preferred), squamous cell (any grade) or usual type adenocarcinoma (grade 1 or 2 only) (preferred), tumor size ≤2 cm, depth of invasion ≤10 mm on LEEP/cone, negative imaging for locoregional disease (MRI recommended).
Cone biopsy with negative margins + SLN mapping or pelvic lymphadenectomy (Preferred)
If surgical nodes are positive, proceed to adjuvant treatment (CERV-6).
Stage IB1 not meeting conservative surgery criteria, or select Stage IB2. Patient desires fertility preservation.
Radical trachelectomy + SLN mapping or pelvic lymphadenectomy ± para-aortic lymphadenectomy (Preferred)
If surgical nodes are positive, proceed to adjuvant treatment (CERV-6).
Stage IA2-IB1, Non-Fertility Sparing

Branching: Conservative surgery criteria met, Tumor size, Histology, LVSI, Margins, Imaging

Stage IA2-IB1 cervical carcinoma; all conservative surgery criteria met (same as above).
Type A hysterectomy + SLN mapping or pelvic lymphadenectomy (Preferred)
Proceed to adjuvant treatment assessment based on findings (CERV-6).
Stage IB1 (not meeting conservative criteria), IB2, IIA1 - Non-Fertility Sparing

Branching: Disease extent, Surgical findings

Stage IB1 not meeting conservative surgery criteria, IB2, or IIA1.
Type C1 radical hysterectomy + SLN mapping or pelvic lymphadenectomy (category 1) ± para-aortic lymphadenectomy (category 2B) (Preferred); Pelvic EBRT + brachytherapy ± concurrent platinum-containing chemotherapy (Other recommended)
For surgical pathway, proceed to adjuvant treatment assessment based on findings (CERV-6).
Stage IB3 and Stage IIA2

Branching: Disease extent, Response to chemoradiation, IGBT feasibility

Stage IB3 and Stage IIA2.
Pelvic EBRT + concurrent platinum-containing chemotherapy + brachytherapy (category 1) (Preferred); Type C1 radical hysterectomy + pelvic lymphadenectomy ± para-aortic lymphadenectomy (category 2B) (Other recommended); Pelvic EBRT + concurrent platinum-containing chemotherapy + brachytherapy + selective completion hysterectomy (category 3 for completion hysterectomy) (Other recommended)
For primary chemoradiation pathway, completion hysterectomy is considered only in select patients with poor response/residual disease or for whom IGBT is not feasible.
Adjuvant Treatment After Surgery

Branching: Nodal status, Margin status, Parametrial status, GOG/Sedlis criteria

Negative nodes, negative margins, negative parametrium.
Observe (Preferred); Pelvic EBRT if combination of risk factors (ie, primary tumor size, stromal invasion, and/or LVSI that meet GOG/Sedlis criteria) (category 1) (Other recommended)
Positive pelvic nodes and/or positive surgical margin and/or positive parametrium. Negative for distant metastases after imaging workup.
EBRT + concurrent platinum-containing chemotherapy (category 1) ± brachytherapy (Preferred)
Positive pelvic nodes and/or positive surgical margin and/or positive parametrium. Positive for distant metastases after imaging workup/biopsy.
Systemic therapy ± individualized EBRT (Preferred)
Para-aortic lymph node positive by surgical staging. Negative for distant metastases.
Extended-field EBRT + concurrent platinum-containing chemotherapy (category 1) ± brachytherapy (Preferred)
Stage IIB-IVA (Locally Advanced)

Branching: Nodal status, Distant metastases, Biomarkers (PD-L1)

Stage IIB-IVA. Negative for distant metastases after imaging workup.
EBRT + concurrent platinum-containing chemotherapy + brachytherapy ± concurrent and maintenance Pembrolizumab (category 1 for FIGO 2014 stage IIIA, IIIB, and IVA; category 2B for select FIGO 2018 stage III–IVA) (Preferred)
Stage IIB-IVA. Positive for distant metastases after biopsy of suspicious areas.
Systemic therapy ± individualized RT (Preferred)
Incidental Finding After Simple/Total Hysterectomy

Branching: Stage, Margin status, LVSI, Conservative surgery criteria met, Distant metastases

Stage IA1. No LVSI, negative margins.
Observe (Preferred)
Stage IA1. No LVSI, negative margins. Pelvic lymphadenectomy performed (preferred).
If negative nodes: Observe; If positive nodes: Adjuvant Treatment (CERV-6) (Preferred)
N/A
Stage IA1 with LVSI and negative margins (or specimen integrity unknown). Negative for distant metastases.
Pelvic EBRT ± brachytherapy ± concurrent platinum-containing chemotherapy (Preferred)
Stage IA2-IB1 cervical carcinoma (based on TH and all conservative surgery criteria met). Negative margins for cancer, No LVSI (preferred). Negative for distant metastases.
Pelvic lymphadenectomy (preferred) (Preferred)
If negative nodes: observe. If positive nodes: Adjuvant Treatment (CERV-6).
Any hysterectomy with a positive margin for cancer (invasive cancer at surgical margin). Negative for distant metastases.
Pelvic EBRT + concurrent platinum-containing chemotherapy + brachytherapy (Preferred)
Stage IB1 (not meeting conservative criteria) – IB2. Negative margins on hysterectomy AND GOG/Sedlis criteria not met.
Pelvic EBRT + brachytherapy ± concurrent platinum-containing chemotherapy (Preferred); Complete parametrectomy/upper vaginectomy + pelvic lymphadenectomy ± para-aortic lymph node sampling (Other recommended)
For surgical pathway, proceed to adjuvant treatment based on findings (positive nodes/margins/parametrium -> CERV-6; negative -> observe).
Surveillance After Primary Treatment

Branching: Stage, Risk of recurrence, Imaging findings, Symptoms

All stages post-treatment.
Interval H&P every 3–6 months for 2 years, then every 6–12 months for 3–5 years, then annually based on risk (Preferred); Cervical/vaginal cytology annually (limited value; consider for immunocompromised or lower genital tract neoplasia detection) (Other recommended); Stage-dependent imaging as clinically indicated (FDG-PET/CT, CT, MRI) for symptoms or examination findings suspicious for recurrence (Preferred); Biopsy ± EUA as clinically indicated to confirm recurrence (Preferred)
Locoregional Recurrence

Branching: Prior RT, Location of recurrence (central vs noncentral), Distant metastases

Locoregional recurrence. No prior radiation therapy or recurrence outside of previous RT field.
Consider surgical resection, if feasible (Preferred); Individualized EBRT + concurrent platinum-containing chemotherapy ± brachytherapy (Preferred)
Locoregional recurrence. Prior RT. Central pelvic disease.
Pelvic exenteration ± intraoperative RT (IORT) (Preferred); Individualized EBRT ± concurrent platinum-containing chemotherapy (Other recommended); Systemic therapy or best supportive care (Other recommended)
Locoregional recurrence. Prior RT. Noncentral disease.
Resection ± IORT (Preferred); Systemic therapy or best supportive care (Other recommended)
Stage IVB or Recurrence with Distant Metastases

Branching: Amenability to local treatment, Biomarkers, Performance status

Distant metastases amenable to local treatment (oligometastatic).
Local treatment: Resection ± individualized EBRT or Local ablative therapies ± individualized EBRT (Preferred); Consider adjuvant systemic therapy (Other recommended)
Distant metastases not amenable to local treatment.
Systemic therapy (Preferred); Best supportive care (Other recommended)
Small Cell Neuroendocrine Carcinoma of the Cervix (NECC) - Primary Workup

Branching: Stage, Tumor size

Stage IA1–IB2 (tumor ≤4 cm).
Radical hysterectomy + SLN mapping or pelvic lymphadenectomy (preferred if suitable for primary surgery) ± para-aortic lymph node sampling (Preferred); Chemoradiation (cisplatin/carboplatin + etoposide) ± brachytherapy (Preferred)
After surgery, adjuvant chemotherapy (Cisplatin/Etoposide or Carboplatin/Etoposide) is recommended.
Stage IB3 (tumor >4 cm).
Chemoradiation + brachytherapy (preferred) (Preferred); Systemic therapy (preferred) or Best supportive care (Preferred)
Small Cell NECC - Locally Advanced Disease (IIA–IVA)

Branching: Treatment response, Disease persistence/recurrence

Stage IIA–IVA. Primary treatment.
Chemoradiation (Cisplatin/Carboplatin + Etoposide) + brachytherapy (preferred) ± chemotherapy (Preferred); Neoadjuvant chemotherapy (Cisplatin/Etoposide or Carboplatin/Etoposide) followed by chemoradiation (Other recommended)
For neoadjuvant pathway, assess response before proceeding to chemoradiation/brachytherapy.
Stage IIA–IVA. Persistent or recurrent disease after primary treatment.
Systemic therapy (preferred) or Best supportive care (Preferred); Consider pelvic exenteration (if local disease) (Other recommended)

Pretreatment EvaluationClick to collapse

History and Physical
Complete history and physical examination
Required (CERV-1)
Assess for distress (use NCCN Distress Thermometer)
Required (CERV-1)
Laboratory
Complete blood count (CBC) including platelets
Required (CERV-1)
Liver function test (LFT)
Required (CERV-1)
Renal function tests (BUN, creatinine)
Required (CERV-1)
Consider HIV testing, especially in younger patients
Category 2A (CERV-1)
Pathology
Cervical biopsy with pathologic review (Principles of Pathology CERV-A)
Required (CERV-1)
Cone biopsy (CKC preferred, LEEP acceptable) as indicated for staging/treatment
Category 2A (CERV-1)
Histologic type (HPV-associated vs. HPV-independent), grade, stromal invasion, LVSI, margin status
Required for pathologic assessment
PD-L1 testing by FDA-approved assay for recurrent, progressive, or metastatic disease
Category 2A (CERV-A)
HER2 IHC testing (with reflex to FISH for equivocal) for advanced, metastatic, or recurrent carcinoma
Category 2A (CERV-A)
Comprehensive molecular profiling (including MMR/MSI, TMB, NTRK, RET) by FDA-approved/CLIA-certified assay for metastatic or recurrent disease
Preferred (CERV-A)
Imaging
Pelvic MRI to assess local disease extent (preferred for Stage IB1-IB3, and when considering conservative surgery)
Preferred (CERV-B)
FDG-PET/CT (preferred) or chest/abdomen/pelvis CT or FDG-PET/MRI to evaluate for metastatic disease in Stage IB1-IB3 and ≥Stage II
Preferred for Stage IB1-IB3 and ≥Stage II (CERV-B)
For small cell NECC: Neck/chest/abdomen/pelvis/groin FDG-PET/CT + brain MRI (preferred) or Chest/abdomen/pelvis CT + brain MRI
Preferred (CERV-B)
Imaging should be based on symptomatology and clinical concern for metastatic disease
Category 2A
Procedures/Consultation
Consider examination under anesthesia (EUA) cystoscopy/proctoscopy (based on symptoms, barrel-shaped lesions, or anterior vaginal involvement)
Category 2A (CERV-1)
Consider options for fertility sparing or referral to reproductive endocrinology and infertility (REI) specialist
Category 2A (CERV-1)
Smoking cessation and counseling intervention
Required (CERV-1)
Avoid
Cytology is not recommended for routine surveillance of recurrent cervical cancer, as its value is limited
Note (CERV-10)
Cytology is not recommended in patients with prior radiation, given limited accuracy
Note (CERV-10)

SurgeryClick to collapse

Primary treatment for early-stage disease (stages IA, IB1, IB2, select IIA1) with curative intent. Also used for fertility preservation in select patients. Salvage surgery (pelvic exenteration) is an option for central pelvic recurrence after prior RT. Surgical staging via lymphadenectomy informs adjuvant therapy.

Surgical Role

Treatment is stratified by stage and histology (CERV 1-5).

Fertility-sparing approaches (conization, trachelectomy) are options for highly selected patients with early-stage, low-risk disease (Stage IA1 with no LVSI, Stage IA2-IB1 meeting conservative criteria). Consultation with REI experts is suggested.

Querleu and Morrow classification (Type A, B, C) describes the extent of hysterectomy. Open abdominal approach is standard (Category 1). Minimally invasive radical hysterectomy is associated with lower DFS and OS in a randomized trial (LACC).

Sentinel lymph node (SLN) mapping is recommended for early-stage disease; best detection in tumors <2 cm. Adherence to the SLN algorithm (side-specific dissection for failed mapping) is critical.

Para-aortic lymphadenectomy is recommended for ≥Stage IB1 disease.

Pelvic exenteration for recurrence should be performed at high-volume centers.

Procedures

Cone Biopsy (Conization)

Diagnostic staging for microinvasive disease; fertility-sparing treatment for Stage IA1 (no LVSI); part of conservative surgery for Stage IA2-IB1 meeting criteria.

Type A Hysterectomy (Simple/Extrafascial)

Non-fertility-sparing treatment for Stage IA1 (no LVSI, negative margins); treatment for Stage IA2-IB1 meeting all conservative surgery criteria (CERV-4).

Type B Radical Hysterectomy (Modified Radical)

Stage IA1 with LVSI and positive carcinoma margins; some cases of Stage IA2-IB1.

Type C1 Radical Hysterectomy

Stage IB1 (not meeting conservative criteria), IB2, IIA1 (Category 1). Nerve-sparing.

Radical Trachelectomy (Vaginal or Abdominal)

Fertility-sparing for Stage IB1 (not meeting conservative criteria), select IB2 (tumors <2 cm).

Pelvic Exenteration (Anterior, Posterior, Total)

Central pelvic recurrence after prior RT, no distant metastasis.

Radiation TherapyClick to collapse

Definitive treatment for locally advanced disease (Stage IB3-IVA) and medically inoperable early-stage disease. Adjuvant treatment after hysterectomy for intermediate-risk (GOG/Sedlis criteria) and high-risk (positive nodes, margins, parametrium) features. Palliative treatment for recurrent/metastatic disease.

Principles

  • CT-based treatment planning with conformal blocking is standard. MRI is best for soft tissue assessment; FDG-PET/CT is useful for nodal volume definition.
  • IMRT is preferred to minimize toxicities in definitive and post-hysterectomy settings.
  • Brachytherapy is a critical component of definitive RT for intact cervix. Image-guided adaptive brachytherapy (IGABT) with MRI improves outcomes.
  • Concurrent platinum-containing chemotherapy (cisplatin, or carboplatin if cisplatin intolerant) is standard with definitive EBRT for locally advanced disease.
  • Optimal results when treatment is completed within 8 weeks.
  • SBRT is not an appropriate routine alternative to brachytherapy.
  • Reirradiation (IORT, brachytherapy, SBRT, IMRT, proton) is highly customized.

Dose Frameworks

NameTotal DoseDose Per FractionFractionsScheduleIndication
Whole Pelvic EBRT (Microscopic Disease)40-45 Gy1.8-2.0 Gy25-28Daily, 5 days/weekInitial treatment for definitive RT (intact cervix) or adjuvant RT post-hysterectomy.
Boost to Gross Nodes (SIB with IMRT)54-63 Gy2.1-2.3 Gy25-30Concurrent with whole pelvis SIBGross unresected nodal disease.
Brachytherapy (Point A Dose, LDR Equivalent)70-80 GyN/A (LDR 40-70 cGy/h)N/AIntracavitary ± interstitialBoost for intact cervix after EBRT.
Brachytherapy (HR-CTV D90, EQD2)≥85 Gy (preferred); 75-80 Gy for very small tumorsN/AN/AImage-guided adaptive (IGABT)Definitive boost for intact cervix.
Post-Hysterectomy Vaginal Cuff Boost15-18 Gy (5-6 Gy x 3 fractions)5-6 Gy2-3HDR brachytherapy to upper 3-4 cmPositive or close vaginal margins after radical hysterectomy, or after total/simple hysterectomy if completion upper vaginectomy not performed.

Approaches

NameDose FractionationConcurrent ChemotherapyIndicationKey TrialToxicities
Definitive Chemoradiation (Intact Cervix)EBRT 45 Gy + concurrent cisplatin ± pembrolizumab, followed by brachytherapy to HR-CTV D90 ≥85 Gy.Cisplatin (preferred) or carboplatin (if cisplatin intolerant).Locally advanced disease (Stage IB3-IVA).KEYNOTE-A18 (Pembrolizumab added for FIGO 2014 stage IIIA-IIIA).Acute: Cystitis, proctitis, diarrhea, fatigue, hematologic toxicity. Late: Fistula, stenosis, bowel/bladder injury.
Adjuvant Radiation (Post-Hysterectomy)EBRT 45-50 Gy to pelvis ± vaginal cuff boost.Cisplatin (category 1 for high-risk: positive nodes/margins/parametrium).High-risk (positive nodes, margins, parametrium) or intermediate-risk (meeting GOG/Sedlis criteria) disease.GOG 92 (Sedlis criteria), GOG 109 (high-risk).Similar to definitive RT.
Adjuvant Extended-Field RadiationEBRT to pelvis and para-aorta to L3/L4 level, 45 Gy.Cisplatin (category 1).Positive para-aortic lymph nodes (confirmed pathologically).GOG studies.Increased risk of renal, bowel, and hematologic toxicity.
ReirradiationHighly individualized (IORT, SBRT, IMRT, brachytherapy, proton).Variable, based on prior therapy and tolerance.Locoregional recurrence after prior RT.N/A.High risk of severe late toxicity (fistula, necrosis).

Systemic TherapyClick to collapse

Systemic therapy is used concurrently with radiation for locally advanced disease, as adjuvant therapy, and as primary treatment for recurrent/metastatic disease. The landscape includes traditional cytotoxic chemotherapy, anti-angiogenic agents (bevacizumab), immune checkpoint inhibitors (pembrolizumab, cemiplimab, atezolizumab, nivolumab), and antibody-drug conjugates (tisotumab vedotin). Treatment selection is increasingly guided by biomarkers (PD-L1, MSI-H/dMMR, TMB-H, HER2, NTRK, RET).

Concurrent with Definitive EBRT (Locally Advanced Disease)
Category 1 evidence from randomized trials showing improved survival with concurrent cisplatin over RT alone. KEYNOTE-A18 adds pembrolizumab for improved PFS/OS in stage III-IVA.
Preferred: Cisplatin ± Pembrolizumab (Category 1 for FIGO 2014 stage IIIA, IIIB, IVA; Category 2B for select FIGO 2018 stage III-IVA). Carboplatin ± Pembrolizumab if cisplatin intolerant.
Adjuvant (After Hysterectomy) - High-Risk
Category 1 evidence (GOG 109) for improved survival with concurrent chemoradiation in high-risk disease (positive nodes/margins/parametrium).
Preferred: Pelvic EBRT + concurrent cisplatin (or carboplatin if cisplatin intolerant) ± brachytherapy.
Recurrent or Metastatic Disease - First-Line
KEYNOTE-826 (pembrolizumab) and BEATcc (atezolizumab) trials demonstrated significant OS/PFS benefits with addition of IO to chemo ± bevacizumab in first-line setting.
Preferred: For PD-L1-positive tumors (CPS ≥1): Cisplatin/Paclitaxel + Pembrolizumab ± Bevacizumab (Category 1) OR Carboplatin/Paclitaxel + Pembrolizumab ± Bevacizumab (Category 1). Cisplatin/Paclitaxel + Bevacizumab (Category 1) OR Carboplatin/Paclitaxel + Bevacizumab. Cisplatin/Paclitaxel + Atezolizumab + Bevacizumab (Category 1) OR Carboplatin/Paclitaxel + Atezolizumab + Bevacizumab (Category 1).
Recurrent or Metastatic Disease - Second-Line/Subsequent
Pembrolizumab approved for TMB-H, PD-L1+, MSI-H/dMMR tumors. Tisotumab vedotin showed OS benefit over chemotherapy in innovaTV-301 trial.
Preferred: TMB-H tumors: Pembrolizumab. PD-L1-positive: Pembrolizumab. MSI-H/dMMR tumors: Pembrolizumab. Tisotumab vedotin-tftv (Category 1).
Recurrent or Metastatic Disease - Biomarker-Directed (Useful in Certain Circumstances)
Tumor-agnostic approvals based on high response rates in basket trials (DESTINY-PanTumor02, SUMMIT, LIBRETTO-001, STARTRK, TRIDENT-1, CheckMate-358, innovaTV 205).
Preferred: HER2-positive (IHC 3+ or 2+): Fam-trastuzumab deruxtecan-nxki. HER2-mutant: Neratinib. RET gene fusion-positive: Selpercatinib. NTRK gene fusion-positive: Larotrectinib, Entrectinib, Repotrectinib. PD-L1-positive: Nivolumab; Pembrolizumab + Tisotumab vedotin-tftv.

Key Regimens

Cisplatin/Paclitaxel + Pembrolizumab ± Bevacizumab
Cisplatin 50 mg/m2 IV Day 1 + Paclitaxel 175 mg/m2 IV Day 1 + Pembrolizumab 200 mg IV Day 1 + Bevacizumab 15 mg/kg IV Day 1
Carboplatin/Paclitaxel + Atezolizumab + Bevacizumab
Carboplatin AUC 5-6 IV Day 1 + Paclitaxel 175 mg/m2 IV Day 1 + Atezolizumab 1200 mg IV Day 1 + Bevacizumab 15 mg/kg IV Day 1
Tisotumab Vedotin-tftv
Tisotumab vedotin-tftv 2.0 mg/kg IV Day 1
Cisplatin/Etoposide + Radiation (for Small Cell NECC)
Cisplatin 50 mg/m2 IV Day 1, 22 + Etoposide 100 mg/m2 IV Days 1-3, 22-24

Treatment Response AssessmentClick to collapse

Title

Response Assessment and Biopsy Logic

Timing

Post-treatment surveillance is based on risk of recurrence. High-risk patients are assessed more frequently (every 3 months for 2 years). Imaging within 3-6 months post-chemoradiation for stage II-IVA. For small cell NECC, reassessment after neoadjuvant chemotherapy is recommended.

Response Logic

  • All recurrences should be proven by biopsy before proceeding to treatment planning for recurrent disease.

  • For suspected recurrence or metastasis, perform neck/chest/abdomen/pelvis/groin FDG-PET/CT and consider pelvis MRI.

  • For small cell NECC, if primary treatment is chemoradiation, FDG-PET/CT ± brain MRI is preferred for assessment. If neoadjuvant chemotherapy is used, reassessment prior to chemoradiation/brachytherapy is recommended.

Imaging Recommendations

  • Surveillance imaging is stage-dependent. For Stage I: based on symptoms/concern. For Stage II-IV: FDG-PET/CT preferred within 3-6 months post-therapy.

  • If first post-treatment FDG-PET/CT is indeterminate, consider repeating in 3 months.

  • For fertility-sparing surgery: Consider pelvic MRI 6 months post-surgery and yearly for 2-3 years.

  • For small cell NECC surveillance: FDG-PET/CT ± brain MRI preferred.

Biopsy Or Salvage Logic

  • Biopsy of suspicious areas is indicated to confirm recurrence/metastasis before systemic therapy.

  • For central pelvic recurrence after prior RT, evaluate for pelvic exenteration (with or without IORT) in carefully selected patients.

  • For recurrent small cell NECC with local disease, consider pelvic exenteration if feasible.

  • For oligometastatic disease, consider local ablative therapies (resection, SBRT) ± systemic therapy.

SurveillanceClick to collapse

Clinical Follow Up Schedule

  • History & Physical Exam: Every 3–6 months for the first 2 years, then every 6–12 months for years 3–5, and annually thereafter [42].
  • More frequent visits (e.g., every 3 months for 2 years) may be considered for high-risk disease [42].
  • Patient education on symptoms of recurrence (e.g., vaginal discharge, bleeding, pain) at each visit [42].

Imaging Strategy

  • Stage I disease: Imaging based on symptoms or clinical concern. For fertility-sparing treatment, consider pelvic MRI 6 months after surgery and yearly for 2–3 years [42,48].
  • Stage II–IV disease: Consider neck/chest/abdomen/pelvis/groin FDG-PET/CT (preferred) or chest/abdomen/pelvis CT within 3–6 months of completing therapy, especially for high-risk features (e.g., positive nodes, parametrial involvement). Consider pelvis MRI at 3–6 months post-therapy [48,49].
  • Stage IVB or Recurrence: Imaging as appropriate (CT, MRI, FDG-PET/CT) to assess response or guide further therapy [48].
  • Biopsy proven recurrence is recommended before salvage therapy [42].

Laboratory Monitoring

  • Complete Blood Count (CBC): As clinically indicated (e.g., during chemotherapy or if symptoms arise) [42].
  • Renal Function (BUN/Creatinine): As clinically indicated, especially with prior cisplatin therapy or impaired renal function [42].
  • Cervical/vaginal cytology: Has limited value in detecting recurrence. May be considered for surveillance of lower genital tract dysplasia, particularly after fertility-sparing surgery. Not recommended post-pelvic radiation due to low accuracy [42,50].
  • Tumor markers: Not routinely recommended. No established serum marker for cervical cancer [42].

Supportive Follow Up

  • Assessment and management of treatment-related late effects (see "late_effects_screening") [44].
  • Counseling on sexual health, including use of vaginal dilators, lubricants/moisturizers, and local estrogen therapy for menopause [45].
  • Smoking cessation counseling and support [44].
  • Referral to Survivorship program as per Principles of Gynecologic Survivorship [37].

ComplicationsClick to collapse

Disease-Related

ComplicationManagement
Hydronephrosis / Renal failureMay occur with stage IIIB disease due to pelvic sidewall extension. Management may include ureteral stenting or nephrostomy as palliative measures or to preserve renal function during treatment [17].
Fistula formation (vesicovaginal, rectovaginal)Rare at diagnosis but can be a complication of advanced disease or treatment. May require surgical repair (e.g., exenteration) or diversion procedures [18].
LymphedemaRisk after pelvic lymphadenectomy. Managed with compression garments, manual lymphatic drainage, and exercise. Sentinel lymph node mapping may reduce risk [19,20].

Supportive CareClick to collapse

Comprehensive supportive care is integral to managing cervical cancer patients, addressing treatment toxicities, nutritional status, psychosocial well-being, and survivorship concerns. Coordination between oncology, primary care, and specialists is essential [37].

Nutritional Support

Assess nutritional status at each visit. Referral to a dietitian is recommended for weight loss >5%, poor oral intake, or malnutrition. Nutritional counseling and support to maintain adequate caloric and protein intake are important, especially during chemoradiation when mucositis and diarrhea may impair intake [37,38].

Anti Emetic Protocol

Follow NCCN Antiemesis Guidelines. High emetogenic chemotherapy (HEC: cisplatin, >24h infusions of carboplatin) warrants a 3-drug regimen: NK1 receptor antagonist + 5-HT3 antagonist + dexamethasone. Moderately emetogenic chemotherapy (MEC: carboplatin AUC <4, paclitaxel, docetaxel) typically uses 5-HT3 antagonist + dexamethasone. Delayed nausea prophylaxis with dexamethasone may be needed for HEC [24].

Gcsf Guidance

Primary G-CSF prophylaxis is recommended for regimens with a high risk (≥20%) of febrile neutropenia (e.g., dose-dense paclitaxel, topotecan, or combination regimens like cisplatin/etoposide for NECC). For intermediate risk regimens (10-20%), consider patient-specific risk factors (age, comorbidities, prior episodes). Use of biosimilar filgrastim or pegfilgrastim is acceptable [21].

Vte Prophylaxis

VTE prophylaxis is recommended for hospitalized patients and for patients receiving anti-angiogenic agents (bevacizumab). Consider pharmacologic prophylaxis (LMWH or DOACs) for high-risk ambulatory patients with cancer, particularly during periods of immobilization or with combination chemotherapy [32].

Pain Management

Assess pain at every visit. Use WHO analgesic ladder. Neuropathic pain (from platinum/taxanes or radiation plexopathy) may require agents like gabapentin, pregabalin, or duloxetine. For bone metastases, consider bone-modifying agents (zoledronic acid, denosumab) and palliative radiation. Refer to pain or palliative care specialists for complex pain [37,39].

Psychosocial Support

Screen for distress using the NCCN Distress Thermometer and Problem List. Provide referrals for psychosocial support (psychotherapy, support groups), financial counseling, and fertility preservation counseling as appropriate. Address survivorship concerns including body image, sexual health, and fear of recurrence [37,40].

Dental Care

Refer for dental evaluation and necessary treatment before starting chemoradiation to mitigate osteonecrosis risk, especially if mandible/maxilla will be in radiation fields. Recommend fluoride trays and regular dental care during and after RT [37,41].

PrognosisClick to collapse

Cervical cancer prognosis varies significantly by stage at diagnosis, with 5-year survival rates ranging from >90% for stage I disease to <20% for distant metastatic disease. The 5-year relative survival rate for all localized cervical cancer is approximately 92%, while for regional disease it is 60%, and for distant metastases it is only 19% [1,2]. The overall 5-year relative survival rate is approximately 67% [2].

Overall Prognosis

By Stage

StageFive Yr SurvivalContext
Stage IA1>95%Excellent prognosis with <1% risk of lymphatic metastasis. Treatment with conization or simple hysterectomy is curative in nearly all cases [3,4].
Stage IA2–IB190–95%Excellent prognosis with treatment. Radical hysterectomy or radiation therapy provides excellent local control. Fertility-sparing approaches are safe in select cases meeting specific criteria [5,6].
Stage IB280–85%Good prognosis. Treatment typically involves radical hysterectomy or definitive chemoradiation, with outcomes dependent on surgical/pathologic risk factors [5,6].
Stage IB3–IIA265–75%Prognosis is primarily driven by response to definitive chemoradiation, which is the standard of care. Adding pembrolizumab to chemoradiation for FIGO 2014 stage III–IVA improves survival [7].
Stage IIB–IVA50–65%Prognosis is dependent on response to definitive chemoradiation. Concurrent platinum-based chemoradiation is standard. The addition of pembrolizumab improves PFS and OS in FIGO 2014 stage III–IVA disease [7,8].
Stage IVB or Recurrence with Distant Metastases<20%Poor prognosis. Treatment is palliative with systemic therapy. Long-term survival is rare, though isolated oligometastatic disease may be amenable to local therapy with systemic treatment [9].

Prognostic Factors

  • Stage at diagnosis (most important factor) [1,2]
  • Lymph node status (positive nodes confer poorer prognosis) [10]
  • Tumor size and depth of invasion [11]
  • Lymphovascular space invasion (LVSI) [11,12]
  • Histologic subtype (e.g., small cell neuroendocrine carcinoma is aggressive with poor prognosis) [13]
  • HPV status (HPV-independent tumors may have worse prognosis) [14]
  • Surgical margin status (positive margins increase recurrence risk) [15]
  • Response to initial chemoradiation [7,8]
  • Performance status [16]

Follow UpClick to collapse

Post Curative Treatment

After completion of curative-intent treatment, follow-up is based on the Society of Gynecologic Oncology (SGO) recommendations, tailored to recurrence risk and patient preference [42].

Surveillance Rationale

The primary goal of surveillance is the early detection of recurrent or metastatic disease, as some recurrences may be amenable to curative-intent salvage therapy. Patient education about symptoms of recurrence (e.g., vaginal discharge, bleeding, pain) is emphasized. While routine imaging and cytology have limited value in detecting asymptomatic recurrences, they are used selectively based on stage and risk [42,43].

Late Effects Screening

  • Screen for genitourinary symptoms: dysuria, frequency, incontinence [44]
  • Screen for gastrointestinal symptoms: chronic diarrhea, rectal bleeding [44]
  • Assess for sexual dysfunction: vaginal dryness, stenosis, dyspareunia [44,45]
  • Evaluate for lymphedema of lower extremities [44]
  • Screen for bone density loss, especially post-oophorectomy or pelvic RT [44]
  • Assess for psychosocial issues: depression, anxiety, fear of recurrence [40]
  • Provide counseling on healthy lifestyle, smoking cessation, and obesity management [44]
  • Discuss second cancer risks (e.g., colon, bladder) relevant to prior RT fields [36]

Recurrence Patterns

Most recurrences occur within the first 2-3 years post-treatment. Patterns include: 1) Local/pelvic recurrence (most common), 2) Distant metastases (e.g., lungs, liver, bone, para-aortic nodes), 3) Combined local and distant recurrence. The location of recurrence influences salvage therapy options (e.g., pelvic exenteration for central pelvic recurrence) [46,47].

Key TrialsClick to collapse

AcronymFull NameYearNInterventionComparatorPopulationPrimary EndpointKey ResultSecondary OutcomesPractice ChangeJournal
KEYNOTE-A18 (ENGOT-cx11/GOG-3047)Pembrolizumab or Placebo with Chemoradiotherapy Followed by Pembrolizumab or Placebo for Newly Diagnosed, High-Risk, Locally Advanced Cervical Cancer20241060Pembrolizumab + concurrent platinum-based chemoradiation (CRT) followed by pembrolizumab maintenancePlacebo + concurrent platinum-based CRT followed by placebo maintenancePreviously untreated, high-risk locally advanced cervical cancer (FIGO 2014 stage IB2–IIB with node-positive disease or stage III–IVA)Progression-Free Survival (PFS) per RECIST v1.1 by investigator assessmentPembrolizumab + CRT significantly improved PFS vs placebo + CRT (HR 0.62, 95% CI 0.49–0.78; P<0.0001). Median PFS: 24.3 vs 16.1 months.Overall Survival (OS): At interim analysis, HR 0.73 (95% CI 0.56–0.95; P=0.013), favoring pembrolizumab. Overall Response Rate (ORR): 93% vs 85%.Established pembrolizumab + concurrent CRT as a new standard of care for high-risk locally advanced cervical cancer, specifically for patients with FIGO 2014 stage IIIA–IIIB–IVA disease.The Lancet
KEYNOTE-826A Phase 3, Randomized, Double-Blind Study of Pembrolizumab (MK-3475) in Combination with Chemotherapy With or Without Bevacizumab for the First-line Treatment of Persistent, Recurrent, or Metastatic Cervical Cancer2021617Pembrolizumab + chemotherapy (± bevacizumab)Placebo + chemotherapy (± bevacizumab)Persistent, recurrent, or metastatic cervical cancer not previously treated with chemotherapyOverall Survival (OS) and Progression-Free Survival (PFS) in PD-L1 CPS ≥1 patientsPembrolizumab significantly improved OS vs placebo in patients with PD-L1 CPS ≥1 (median OS 28.6 vs 16.5 months; HR 0.60, 95% CI 0.49–0.74; P<0.0001). PFS also significantly improved (median 10.5 vs 8.2 months; HR 0.62, 95% CI 0.51–0.76; P<0.001).ORR: 68.1% vs 50.2% in PD-L1 CPS ≥1 group. Duration of response (DoR): median 18.0 vs 10.4 months.Established pembrolizumab + chemotherapy (± bevacizumab) as a preferred first-line standard for recurrent/metastatic cervical cancer with PD-L1 CPS ≥1.New England Journal of Medicine
GOG 240A Randomized Phase III Trial of Cisplatin-based Chemotherapy with or without Bevacizumab in Patients with Advanced, Recurrent, or Persistent Cervical Cancer2014452Chemotherapy (paclitaxel + cisplatin or paclitaxel + topotecan) + bevacizumabChemotherapy alonePersistent, recurrent, or metastatic cervical cancer with no prior chemotherapy for advanced diseaseOverall Survival (OS)Addition of bevacizumab significantly improved OS (median 16.8 vs 13.3 months; HR 0.77, 95% CI 0.64–0.94; P=0.013). PFS was also improved (median 8.3 vs 6.2 months; HR 0.68, P<0.001).ORR: 48% vs 36%. No significant difference in patient-reported quality of life.Established bevacizumab as a key component of first-line therapy for recurrent/metastatic cervical cancer, leading to its approval and inclusion as a preferred regimen component.New England Journal of Medicine
BEATcc (ENGOT-Cx10/GEICO 68C/JGOG1084/GOG-3030)A Randomized, Open-Label, Phase 3 Trial of Atezolizumab Plus Bevacizumab and Chemotherapy for Metastatic, Persistent, or Recurrent Cervical Cancer2024410Atezolizumab + bevacizumab + chemotherapy (cisplatin/carboplatin + paclitaxel)Bevacizumab + chemotherapy (cisplatin/carboplatin + paclitaxel)Previously untreated metastatic, persistent, or recurrent cervical cancer not amenable to curative surgery/radiationProgression-Free Survival (PFS)Atezolizumab combination significantly improved PFS (median 13.7 vs 10.4 months; HR 0.62, 95% CI 0.49–0.78; P<0.0001). Interim OS also improved (median 32.1 vs 22.8 months; HR 0.68, 95% CI 0.52–0.88; P=0.0046).ORR: 84% vs 72%. Duration of response longer with atezolizumab.Established atezolizumab + bevacizumab + chemotherapy as another preferred first-line regimen for recurrent/metastatic cervical cancer, regardless of PD-L1 status in exploratory analysis.The Lancet
innovaTV 301 (ENGOT-cx12/GOG-3057)A Phase 3, Randomized, Open-Label Study of Tisotumab Vedotin Versus Investigator's Choice of Chemotherapy in Patients With Recurrent or Metastatic Cervical Cancer With Disease Progression On or After Chemoradiation2024502Tisotumab vedotinInvestigator's choice chemotherapy (topotecan, vinorelbine, gemcitabine, irinotecan, or pemetrexed)Recurrent or metastatic cervical cancer with disease progression on or after chemotherapy (most had 1 prior line of systemic therapy in the metastatic setting)Overall Survival (OS)Tisotumab vedotin significantly improved OS (median 11.5 vs 9.5 months; HR 0.70, 95% CI 0.54–0.89; P=0.004). PFS also improved (HR 0.67, P<0.0001). ORR: 17.8% vs 5.2%.Duration of response: median 10.3 vs 6.9 months. Safety profile consistent with known effects of TV.Established tisotumab vedotin as a preferred second-line or later therapy for recurrent/metastatic cervical cancer after progression on chemotherapy.New England Journal of Medicine
EMPOWER-Cervical 1 (GOG-3016/ENGOT-cx9)A Randomized, Open-Label, Phase 3 Study of Cemiplimab Versus Investigator's Choice Chemotherapy for the Treatment of Patients With Recurrent or Metastatic Cervical Cancer2022608CemiplimabInvestigator's choice chemotherapy (topotecan, vinorelbine, gemcitabine, irinotecan, pemetrexed)Recurrent or metastatic cervical cancer who progressed on or after platinum-based chemotherapyOverall Survival (OS)Cemiplimab significantly improved OS (median 12.0 vs 8.5 months; HR 0.69, 95% CI 0.56–0.84; P<0.001). Final analysis at 47.3 months follow-up confirmed OS benefit (HR 0.67). ORR: 16% vs 6.3%.PFS: median 2.8 vs 2.9 months (HR 0.75). Benefit observed regardless of PD-L1 status, though greater magnitude in CPS ≥1 subgroup.Established cemiplimab as an other recommended second-line or subsequent therapy for recurrent/metastatic cervical cancer.New England Journal of Medicine
CheckMate 358Nivolumab With or Without Ipilimumab in Patients With Recurrent or Metastatic Cervical Cancer2024176 (across cohorts, 112 received NIVO1+IPI3 regimen)"Nivolumab + ipilimumab (NIVO1+IPI3 schedule: nivolumab 1 mg/kg + ipilimumab 3 mg/kg Q3W x4 doses, then nivolumab 240 mg Q2W)Nivolumab monotherapy (NIVO3) or different schedule (NIVO3+IPI1)Recurrent or metastatic cervical cancer (HPV-associated) with progression on or after chemotherapyObjective Response Rate (ORR)For the randomized NIVO1+IPI3 arm, ORR was 40% (95% CI 26–56). The pooled NIVO1+IPI3 schedule had ORR of 38%. Nivolumab monotherapy ORR was 26%.Duration of response not reached for many patients. Safety profile consistent with known irAEs for the combination.Supported the addition of ipilimumab + nivolumab as an other recommended second-line or subsequent therapy option for recurrent/metastatic cervical cancer.The Lancet Oncology
LACCPhase III Randomized Trial of Laparoscopic or Robotic Versus Abdominal Radical Hysterectomy in Patients With Early-Stage Cervical Cancer2018631Minimally invasive radical hysterectomy (MIS: laparoscopic or robotic)Open abdominal radical hysterectomyPatients with stage IA1 (with LVSI) to IB1 cervical cancerRate of disease-free survival (DFS) at 3 yearsMIS was associated with lower 3-year DFS (91.2% vs 97.1%; HR 3.74, 95% CI 1.63–8.58) and lower 3-year OS (93.8% vs 99.0%; HR 6.00, 95% CI 1.77–20.30).Higher rate of adjuvant therapy in MIS group. No difference in perioperative complications.Changed surgical practice to favor open abdominal radical hysterectomy for early-stage cervical cancer, as MIS was found to be inferior for oncologic outcomes.New England Journal of Medicine
SHAPESimple Versus Radical Hysterectomy in Women With Low-Risk Cervical Cancer2024700Simple (extrafascial) hysterectomy with pelvic lymph node assessmentRadical hysterectomy (type B/C) with pelvic lymph node assessmentLow-risk cervical cancer (tumor ≤2 cm, limited stromal invasion, node-negative)Pelvic recurrence at 3 yearsNon-inferiority of simple hysterectomy was demonstrated. 3-year pelvic recurrence rate: 2.52% (simple) vs 2.17% (radical). The difference was within the pre-specified non-inferiority margin.Significantly lower rate of urinary retention with simple hysterectomy (0.6% vs 11% at 4 weeks, P<0.001). Similar rates of adjuvant therapy.Supports the use of simple hysterectomy with lymph node assessment as a standard treatment option for low-risk early-stage cervical cancer (tumor ≤2 cm, no LVSI, negative margins), offering less morbidity.New England Journal of Medicine

Clinical PearlsClick to collapse

  • Pearl 1: The LACC trial established open abdominal radical hysterectomy as the standard over minimally invasive approaches for early-stage cervical cancer due to superior oncologic outcomes [58].
  • Pearl 2: The SHAPE trial demonstrated that simple hysterectomy is non-inferior to radical hysterectomy for low-risk early-stage cervical cancer (tumor ≤2 cm, no LVSI) when combined with pelvic lymph node assessment [57].
  • Pearl 3: SENTINEL lymph node mapping is now standard for surgical staging in early-stage disease, but adherence to the algorithm (side-specific dissection for failed mapping) and ultrastaging of SLNs are critical [19,59].
  • Pearl 4: Concurrent cisplatin-based chemoradiation is the standard of care for stage IB3–IVA, with a 30–50% reduction in risk of death compared to radiation alone [8,60].
  • Pearl 5: The addition of pembrolizumab to concurrent chemoradiation improves PFS and OS for patients with FIGO 2014 stage III–IVA cervical cancer (KEYNOTE-A18) [7].
  • Pearl 6: PD-L1 testing (CPS ≥1) is required to guide first-line pembrolizumab-based therapy and second-line pembrolizumab monotherapy in recurrent/metastatic disease [27,61].
  • Pearl 7: Comprehensive molecular profiling (including HER2, MSI/TMB, NTRK, RET) should be considered for all patients with recurrent or metastatic disease to identify actionable targets for second-line therapy [14,62].
  • Pearl 8: Vaginal dilator use post-radiation is recommended to prevent vaginal stenosis and maintain sexual function [45].

Special SituationsClick to collapse

Incidental Finding of Invasive Cervical Cancer After Simple/Total Hysterectomy
Cervical Cancer in Pregnancy
Small Cell Neuroendocrine Carcinoma of the Cervix (NECC)
Fertility Preservation

Guidelines ResourcesClick to collapse

NCCN Clinical Practice Guidelines in Oncology: Cervical Cancer, Version 2.2025
SGO Clinical Practice Guideline: Follow-up for Gynecologic Cancer Survivors
Radiation Therapy for Cervical Cancer: Executive Summary of an ASTRO Clinical Practice Guideline
Guidelines for Cervical Cancer Screening
ESMO Clinical Practice Guidelines for the Management of Cervical Cancer

Protective FactorsClick to collapse

  • HPV vaccination — Immunization against HPV prevents infection with the types of HPV against which the vaccine is designed and is expected to prevent specific HPV cancer. HPV vaccines may also decrease the incidence of both squamous cell carcinoma and adenocarcinoma [MS-2].
  • Effective cervical cancer screening (cytology and/or HPV testing) — The substantial decline in incidence and mortality of SCC of the cervix in developed countries is presumed to be the result of effective screening [MS-2].
  • Smoking cessation and abstinence — Smoking cessation should be advised in current smokers, and former smokers should continue to avoid smoking [MS-3].