Screening
Cervical cancer screening can detect pre-invasive disease and help reduce the risk of cervical cancer. Screening involves one or both of:[80][81][106]
Cervical cytology testing (Pap smear or liquid-based cytology) to identify precancerous lesions or cancerous cells on the cervix
Human papillomavirus (HPV) testing to identify the presence of high-risk subtypes of HPV
The cervical cancer screening examination should be limited to visual inspection of the cervix and cervical swabs for cytology and/or HPV; it should not include a full pelvic examination.
HPV testing, either alone or in combination with cytology testing, appears to be more sensitive than and superior to cytology alone.[31][83][84] A negative high-risk HPV test provides greater reassurance of a low risk of high-grade dysplasia (cervical intra-epithelial neoplasia [CIN] 3) compared with a negative cytology test. However, HPV testing has a higher false-positive rate and may increase unnecessary referrals and interventions (e.g., colposcopy and biopsy).[83][85] HPV testing is carried out using validated DNA-based high-risk HPV screening tests.
Women should continue to have cervical cancer screening even if they have been immunised for HPV; the long-term impact of vaccination on HPV and cytology testing is not yet known.[106]
Cervical cancer screening recommendations: average risk women
The American Cancer Society (ACS) recommends primary HPV testing every 5 years starting at age 25 years, and continuing to 65 years. If primary HPV testing is not available, women should be offered either co-testing (HPV testing combined with cytology) every 5 years or cytology testing alone every 3 years.
Draft recommendations from the US Preventive Services Task Force (USPSTF) recommend cytology testing every 3 years starting at age 21-29 years, followed by clinician- or patient-collected high-risk HPV primary screening every 5 years from ages 30 to 65 years. Alternatively, women aged 30-65 years can continue with screening every 3 years with cervical cytology alone, or screening every 5 years with high-risk HPV testing in combination with cytology (co-testing).
Screening should stop in women older than age 65 years if they have had adequate prior screening and are not otherwise at high risk for cervical cancer.
Average-risk women of any age should not be screened after hysterectomy (with removal of the cervix) if they have no history of CIN 2 (or higher) or cervical cancer.
In the UK:[107]
The NHS Cervical Screening Programme offers an HPV screening test to women every 3 years from age 25-49 years, and every 5 years from age 50 to 64 years.
Guidelines provide further advice on follow-up strategies for abnormal cervical screening tests, based on age, and current and past cytological abnormalities.[90][91][108] Positive primary HPV screening should trigger reflex cytology testing.[90]
The World Health Organization (WHO) recommends:[109][110]
HPV DNA detection as the primary screening test, starting at the age of 30 years with regular screening every 5 to 10 years, using either a:
screen-and-treat approach (decision to treat based on a positive primary screening test alone), or
screen, triage and treat approach (decision to treat based on a positive primary screening test followed by a positive second test [triage], with or without histologically confirmed diagnosis).
Existing programmes with quality-assured cytology should continue until HPV DNA testing is operational, but those using visual inspection with acetic acid (VIA) should transition rapidly due to challenges with quality assurance. In the absence of HPV DNA testing, WHO suggests a regular screening interval of every 3 years when using VIA or cytology testing.
For women >50 years, screening is stopped after two consecutive negative screening results consistent with the recommended regular screening intervals.
HPV DNA is the recommended screening test. HPV mRNA detection is an alternative primary screening test, with or without triage, with regular screening every 5 years. If HPV mRNA testing is used, there should be capacity to provide follow-up screening at 5-year intervals.
Cervical cancer screening recommendations: higher-risk women
Women with HIV have an increased risk of cervical cancer compared with women without HIV.[8][9][111]
US guidelines from the Centers for Disease Control and Prevention, the National Institutes of Health, and HIV Medicine Association of the Infectious Diseases Society of America, make the following age-specific recommendations for women with HIV:[71]
<30 years of age
Start cervical cancer screening at age 21 years, which should continue throughout their lifetime
Women aged 21 to 29 years should have cervical cytology at initial diagnosis of HIV, and then every 12 months if results are normal. If the results of three consecutive cytology tests are normal, follow-up cytology should be every 3 years. Co-testing (cytology and high-risk HPV testing) and reflex high-risk HPV testing (i.e., HPV testing in the presence of abnormal cytology results) are not routinely recommended for women with HIV <30 years, although they may be considered for women aged 25 to 29 years with HIV.
≥30 years of age
Women aged 30 years and older can undergo cervical cancer screening with cytology alone or HPV co-testing:
Women undergoing cytology alone should have cytology at initial diagnosis of HIV, and then every 12 months if results are normal. If the results of three consecutive cytology tests are normal, follow-up cytology should be every 3 years.
Women undergoing HPV co-testing should have co-testing at initial diagnosis of HIV or at age 30 years, and then every 3 years if results are negative (i.e., a normal cytology test and negative HPV test).
Cervical screening should continue throughout the woman’s life, and should not stop at a specified age (as for the general population).
Primary HPV testing (high-risk HPV [hrHPV] testing alone) is not recommended in women with HIV.
WHO makes the following recommendations for women with HIV:[109]
HPV DNA detection as the primary screening test in a screen, triage and treat approach, starting at the age of 25 years with regular screening every 3 to 5 years.
In the absence of HPV DNA testing, a regular screening interval of every 3 years when using VIA or cytology testing.
For women >50 years, screening is stopped after two consecutive negative screening results consistent with the recommended regular screening intervals.
Reporting of cervical cytology results
Results are commonly reported using the Bethesda system:[86][87]
Normal (negative for intra-epithelial lesion or malignancy)
Epithelial cell abnormality
Squamous cell
Atypical squamous cells of undetermined significance (ASC-US)
Atypical squamous cells, cannot exclude high-grade squamous intra-epithelial lesion (ASC-H)
Low-grade squamous intra-epithelial lesion (LSIL); encompassing HPV infection, mild dysplasia, and CIN 1
High-grade squamous intra-epithelial lesion (HSIL); encompassing moderate and severe dysplasia, carcinoma in situ, CIN 2, and CIN 3 on biopsy
HSIL with features suspicious for invasion (if suspected)
Squamous cell carcinoma.
Glandular cell
Atypical glandular cells (AGC); may be endocervical, endometrial, or glandular cells
AGC, favour neoplastic; may be endocervical or glandular cells
Endocervical adenocarcinoma in situ (ACIS)
Adenocarcinoma.
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