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      News & Perspective Drugs & Diseases CME & Education Academy Video Decision Point
      Drugs & Diseases > Obstetrics & Gynecology

      Cervical Cancer Guidelines

      Updated: May 13, 2022
      • Author: Cecelia H Boardman, MD; Chief Editor: Leslie M Randall, MD, MAS, FACS  more...
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      Guidelines

      Guidelines Summary

      Guideline Contributor:  Jori S Carter, MD, MS Assistant Professor, Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Virginia Commonwealth University School of Medicine

      Screening

      Cervical cancer screening has traditionally used the Pap smear (conventional or liquid-based cytology). More recently, cytology has been supplemented by human papillomavirus (HPV) testing. Samples for these tests may be taken during a pelvic examination, along with visual inspection of the cervix, but the pelvic examination itself is not part of the screening process for cervical cancer. [51]

      Guidelines on cervical cancer screening have been issued by the following organizations:

      • American Cancer Society (ACS)
      • American Congress of Obstetrics and Gynecology (ACOG)
      • American College of Physicians (ACP)
      • American Society of Clinical Pathology (ASCP)
      • American Society of Colposcopy and Cervical Pathology (ASCCP)
      • U.S. Preventive Services Task Force (USPSTF)

      In May 2012, the ACS, the ASCCP, and the ASCP issued joint guidelines for cervical cancer screening, [3] followed shortly thereafter by updated guidelines from the USPSTF, whose recommendations are consistent with those of the ACS, ASCCP, and ASCP. [4] In November 2012, ACOG issued new screening guidelines that were also consistent with the recommendations of these groups. [2] In April 2015, the ACP issued best practice advice on cervical cancer screening in average-risk women; the recommendations were supported by ACOG and endorsed by ASCP. Screening recommendations for specific patient groups are as follows [3, 4, 2] :

      Table 1. Cervical Cancer Screening Recommendations

      Table. 1 (Open Table in a new window)

      Patient Status

      Recommended Screening Method

      Comments

      < 21 years old

      No screening

       Sexual history is not a consideration

      21-29 years old

      Cytology alone every 3 years

      		  

      30-65 years old

      Preferred: HPV and cytology co-testing every 5 years

      Acceptable: Cytology alone every 3 years

      		  

      >65 years old

      Screening can be discontinued after either three consecutive negative cytology tests or two negative cytology and HPV tests within 10 years, provided the most recent test was within 5 years

      Women with a history of cervical intraepithelial neoplasia (CIN) 2, CIN 3, or adenocarcinoma in situ should continue routine age-based screening for at least 20 years

      After total hysterectomy

      No screening necessary

      Applies to women without a cervix and without a history of CIN 2, CIN 3, adenocarcinoma in situ, or cancer in the past 20 years

      After HPV vaccination

      Follow the same age-specific recommendations as unvaccinated women

      		  

      Although current guidelines advise against performing HPV testing in women younger than 30 years of age, and do not recommend HPV testing alone for primary cervical cancer screening, a growing body of evidence calls these recommendations into question. In April 2015, a panel of experts that included representatives from seven relevant organizations issued interim guidance that supports primary HPV testing as a reasonable technique for cervical cancer screening. [108]

      The USPSTF updated their draft recommendations in 2017 and 2018 to recommend high-risk HPV testing alone every 5 years as an alternative to cytology screening alone every 3 years in women 30 years of age and older; or cotesting every 5 years. [55, 109]

      ACOG guidelines for cervical cancer screening in HIV-positive women are as follows [2] :

      • HIV-positive women represent an exception to the recommendation against starting screening before age 21
      • HIV-positive women younger than 30 yr can undergo cytology testing once every 3 yr instead of annually if they have had three consecutive normal annual cytology tests
      • ACOG recommends against cotesting for women younger than 30 yr
      • Women with HIV who are 30 yr of age or older can undergo either testing with cytology alone or cotesting with cytology and HPV testing; those with three consecutive normal annual cytology tests can then be screened annually, and those with one normal cotest result can also be screened annually

      Management of Abnormal Screening Results

      In 2013, both the American Society for Colposcopy and Cervical Pathology (ASCCP) and the American Congress of Obstetricians and Gynecologists (ACOG) released updated guidelines for managing women with abnormal cervical cancer screening results and diagnosed cancer precursors.

      ASCCP and ACOG each provided detailed management algorithms for the following scenarios: [57, 110]

      • Women age 30 or older who are cytology negative but HPV positive
      • Women with atypical squamous cells of undetermined significance (ASC-US) on cytology
      • Women 21-24 years of age with either ASC-US or low-grade squamous intraepithelial lesion (LSIL)
      • Women with LSIL
      • Women 21-24 years of age with atypical squamous cells, cannot rule out high-grade SIL (ASC-H) and high-grade squamous intraepithelial lesion (HSIL)
      • Women with HSIL
      • Initial workup of patients with atypical glandular cells (AGC)
      • Subsequent management of patients with AGC
      • Women with no lesion or biopsy-confirmed grade 1 cervical intraepithelial neoplasia (CIN1) preceded by "lesser abnormalities"
      • Women with no lesion or biopsy-confirmed CIN1 preceded by ASC-H or HSIL cytology
      • Women 21-24 years of age with no lesion or biopsy-confirmed CIN1
      • Young women with biopsy-confirmed grade 2 or 3 cervical intraepithelial neoplasia (CIN 2,3)
      • Young women with biopsy-confirmed CIN 2,3 in special circumstances

      ASCCP also provided management algorithms for the following scenarios [57] :

      • Women with unsatisfactory cytology
      • Women with negative cytology but endocervical/transformation zone absent or insufficient
      • Pregnant women with LSIL
      • Women with atypical squamous cells; cannot exclude ASC-H
      • Women diagnosed with adenocarcinoma in situ (AIS) during a diagnostic excisional procedure

      The ASCCP consensus guidelines, which are also endorsed by the National Comprehensive Cancer Network (NCCN), include the following major recommendations [57] :

      • If either (but not both) Pap smear or HPV testing yields positive results, co-testing is integrated into follow-up care; colposcopy, HPV DNA typing, or both may be indicated
      • Return to "routine" screening in women treated for cervical cancer
      • Colposcopy may be required for women with positive HPV results or with repeated unsatisfactory cytological findings that are missing endocervical or transformation zone components

      The ACOG recommendations fall into three categories: those based on consistent scientific evidence, those based on limited and/or inconsistent scientific evidence, and those primarily based on consensus and expert opinion. Major recommendations with consistent scientific evidence include the recommended screening outlined in Table 1, above, and the following [110, 2] :

      • For women with ASC-US, reflex HPV testing is preferred
      • For women with HPV-positive ASC-US, whether identified on reflex HPV testing or co-testing, colposcopy is recommended
      • For women with LSIL and no HPV test or a positive HPV test result, colposcopy is recommended
      • For women with a histologic diagnosis of cervical intraepithelial neoplasia (CIN) 2, CIN 3, or CIN 2,3 and adequate colposcopic examination, both excision and ablation are acceptable treatment modalities, except in pregnant women and young women

      The ACOG guidelines note that women with any of the following risk factors may require more frequent cervical cancer screening than is recommended in the routine screening guidelines, which were intended for average-risk women:

      • HIV infection
      • Immunocompromise (eg, solid organ transplant recipients)
      • Exposure to diethylstilbestrol in utero
      • Previous treatment for CIN 2, CIN 3, or cancer

      Prevention

      With rare exceptions, cervical cancer results from genital infection with HPV, which is a known human carcinogen. The U.S. Advisory Committee on Immunization Practices (ACIP) has issued the following recommendations for HPV vaccination [111] :

      • Routine vaccination of girls or boys aged 11-12 years with 2 or 3 doses of HPV9
      • Previously unvaccinated females and males aged 13-26 years
      • Children as young as 9 years may be vaccinated, particularly if there is a history of sexual abuse or assault
      • Any man who has sex with a man and individuals with compromised immune systems (including people with HIV infection/AIDS), through age 26, if they were not fully vaccinated when they were younger
      Next:

      Staging

      In the International Federation of Gynecology and Obstetrics (Federation Internationale de Gynecologie et d’Obstetrique [FIGO]) guidelines for staging, procedures are limited to the following [50] :

      • Colposcopy
      • Biopsy
      • Conization of cervix
      • Cystoscopy
      • Proctosigmoidoscopy

      The National Comprehensive Cancer Network (NCCN) guidelines include the addition of CT, MRI, combined PET-CT and surgical staging to guide treatment options. While the NCCN notes that cervical cytology and cervical biopsy generally results in an accurate diagnosis, cone biopsy (conization) is recommended if the cervical biopsy is inadequate to define invasiveness. [112]

      Previous
      Next:

      Treatment

      The European Society for Medical Oncology (ESMO) and the National Comprehensive Cancer Network (NCCN) have both released guidelines for the management of cervical cancer. [112, 113]

      In addition, the American Society for Clinical Oncology has released fertility preservation guidelines for adults with cancer. General recommendations include the following [114] :

      • The possibility of infertility should be addressed as early as possible before treatment starts

      • Refer patients who express an interest in fertility preservation (and patients who are ambivalent) to reproductive specialists

      • Answer basic questions about whether fertility preservation may have an impact on successful cancer treatment

      Specific recommendations for treating women with cervical cancer include the following [114] :

      • Radical trachelectomy should be restricted to stage IA2 to IB cervical cancer with diameter < 2 cm and invasion < 10 mm

      • Both embryo and oocyte cryopreservation should be offered as established fertility preservation methods

      • Offer cryopreservation of unfertilized oocytes as an option for patients who do not have a male partner, do not wish to use donor sperm, or have religious or ethical objections to embryo freezing

      • Ovarian transposition (oophoropexy) is an option when pelvic radiation therapy is performed; however, because of radiation scatter, ovaries are not always protected, and patients should be aware that this technique is not always successful

      Early-stage (IA1) disease

      ESMO and NCCN guidelines are in agreement that the treatment of choice for stage IA1 disease with no lymphovascular space invasion (LVSI) is fertility-sparing cone biopsy, or if preservation of fertility is not relevant, simple hysterectomy. For stage IA1 with LVSI, a cone biopsy or hysterectomy with lymphadenectomy is recommended; the NCCN recommends modified radical hysterectomy, while ESMO recommends extrafascial hysterectomy. [112, 113]

      According to the NCCN guidelines, postoperative pelvic radiation therapy (with or without concurrent cisplatin chemotherapy) is a category 1 recommendation for women with stage IA disease and negative lymph nodes after surgery who have high-risk cervical factors (eg, a large primary tumor, deep stromal invasion, and/or lymphovascular space invasion). [112]

      Stage IA2 disease

      The NCCN and ESMO provide recommendations that include the following [112, 113] :

      • Fertility-sparing radical trachelectomy (NCCN) and pelvic lymph node dissection

      • Cone biopsy followed by observation is acceptable, if the margins and lymph node dissection are negative

      • For patients who do not desire fertility preservation, modified radical hysterectomy (NCCN) or extrafascial hysterectomy (ESMO) and bilateral pelvic lymph node dissection; ESMO recommends radical trachelectomy or radical hysterectomy with lymph node dissection when LVSI is present

      • Pelvic radiation with brachytherapy (NCCN) or brachytherapy alone (ESMO) is recommended as an alternative option

      Stage IB or IIA

      According to NCCN guidelines, fertility-sparing radical trachelectomy and pelvic lymph node dissection is an option only for stage IB1 with tumors ≤2 cm. However, fertility-sparing treatment is not recommended for stage IB1 small-cell neuroendocrine histology and adenoma malignum.10 ESMO guidelines recommend either radical trachelectomy or conization with/without chemotherapy are offered as a fertility-preserving option to stage IB1 patients. [54]

      NCCN and ESMO non–fertility-sparing recommendations for stage IB or IIA are as follows [113] :

      • Radical hysterectomy and bilateral pelvic lymph node dissection: preferred for stages IB1 or IIA1; alternative treatment for stages IB2 or IIA2

      • Concurrent chemoradiation is the preferred treatment for stages IB2 or IIA2

      • Pelvic radiotherapy and brachytherapy with or without concurrent cisplatin-based chemotherapy is also acceptable for patients with stage IB1 or IIA1 disease

      ESMO found no evidence that chemoradiation would be useful in patients with stages IB1 or IIA and tumors < 4 cm. [113]

      Advanced Disease

      The NCCN acknowledges that traditionally, advanced disease included stages IIB-IVA; however, many oncologists now also include patients with IB2 and IIA2 in the advanced disease category. The NCCN advises that concomitant chemoradiation and brachytherapy is the standard of care. Radiation therapy is given in four to six cycles of 1.8-2 Gy, with one of the following cisplatin-based chemotherapy regimens [112] :

      • Cisplatin 40 mg/m2 IV once weekly (not to exceed 70 mg/wk) or

      • Cisplatin 50-75 mg/m2 IV on day 1 plus  5-fluorouracil (5-FU) 1000 mg/m2 continuous IV infusion on days 2-5 and days 30-33 (total dose 4000 mg/m2 each course) or

      • Cisplatin 50-75 mg/m2 IV on day 1 plus  5-FU 1000 mg/m2 continuous IV infusion over 24 h on days 1-4 (total dose 4000 mg/m2 each cycle) every 3 wk for a total of three to four cycles

      The ESMO guidelines provide similar recommendations. [113]

      In 2016, the American Society of Clinical Oncology (ASCO) issued its first clinical practice guideline on invasive cervical cancer. The guideline is "resource-stratified," and gives treatment recommendations that are tailored to the availability of healthcare resources in specific regions. [115, 116] :

      Some of the key recommendations are:

      • In basic settings, where radiation therapy is not an option, extrafascial hysterectomy, either alone or after chemotherapy, can be an option for women with stage IA1 to IVA cervical cancer.

      • Concurrent radiotherapy and chemotherapy is the standard of care in enhanced and maximal settings for women with stage IB to IVA disease. The addition of concurrent low-dose chemotherapy with radiotherapy is emphasized, but not at the cost of delaying radiation therapy if chemotherapy is not available.

      • In limited-resource settings where brachytherapy is not available, extrafascial hysterectomy or a modification in patients who have residual tumor 2 to 3 months after concurrent chemoradiotherapy and additional boost is recommended.

      • Patients with stage IV or recurrent cervical cancer in basic settings can receive single-agent chemotherapy (carboplatin or cisplatin).

      • For patients who cannot be treated with curative intent, palliative radiotherapy should be used to relieve symptoms of pain and bleeding, if resources are available.

      • In settings of scarce resources, single- or short-course radiotherapy regimens can used for retreatments, if feasible, for persistent or recurrent symptoms.

      • If follow-up care is available, cone biopsy is recommended for women with stage 1A2 disease in basic-resource settings, and cone biopsy plus pelvic lymphadenectomy is recommended in limited settings. For patients in enhanced and maximal settings, radical trachelectomy is recommended for those with stage IB1 cervical cancer with tumor size up to 2 cm who desire fertility-sparing surgery.

      Metastatic Disease

      The NCCN and ESMO recommend cisplatin-based chemotherapy on a palliative basis. [112, 113] The NCCN further recommends that radiation therapy may be considered for control of bleeding and pain. In addition, for second-line therapy, docetaxel, gemcitabine, ifosfamide, 5-fluorouracil, mitomycin, irinotecan, and topotecan may be considered (category 2B recommendation), as well as pemetrexed and vinorelbine (category 3 recommendation). Bevacizumab as single-agent therapy is also acceptable. [112]

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