In 2014, there were an estimated 12,000 new cases of cervical cancer and 4,000 deaths from cervical cancer in the United States. The incidence of cervical cancer is highest in women younger than 50 years of age and is more prevalent in Hispanic and black women. Fifty percent of women diagnosed with cervical cancer have never been screened, and an additional 10 percent have not been screened in the five years prior to diagnosis.
For decades, cervical cancer screening was performed by cytology (Pap smear) with cells taken from the epithelial migratory zone of the cervix. More recently, screening for HPV, the pathogen associated with the development of most cervical cancers, has also become part of the screening regimen.
In the December 3, 2014 issue of JAMA, the guidelines for cervical cancer screening developed by the American College of Obstetricians and Gynecologists (ACOG) were published.
Key recommendation points.
Cervical cancer screening should begin at age 21, with no prior screening regardless of sexual activity or risk group.
For women aged 21-29 years, cervical cytology should be performed every three years.
For women aged 30-65 years, cervical cytology and combined human papillomavirus (HPV) screening should be performed every five years, or every three years as an alternative screening method.
Women at high risk for cervical cancer should be screened more frequently (HIV infection, immunocompromise, uterine exposure to hexestrol, or the presence of cervical intraepithelial neoplasia [CIN]2, CIN3, or cancer).
Screening may be discontinued in women older than 65 years of age (3 consecutive negative cytology results or 2 consecutive negative combined results in the last 5 years of the previous 10 years) if negative screening results are evident and there are no lesions of CIN grade 2 or higher.
Cervical cells can be collected by liquid or conventional cervical smear.
HPV testing alone cannot be used as a screening test.
If the results of the combined test show cytologic findings of atypical squamous cells of undetermined significance (ASCUS) and negative HPV, routine screening will continue according to age.
If the results of the combined test show negative cytologic results and positive HPV results, the combined test should be repeated within 12 months or a special HPV genotype test should be performed.
Screening recommendations are consistent regardless of whether a woman has received HPV vaccine.
Source features of the guidelines.
The cervical cancer screening guidelines are published by ACOG, a nonpublic, nonprofit, voluntary organization with 55,000 physician members. Two clinical review panels of obstetricians and gynecologists participated in the development of this guideline, and the final version was reviewed and approved by the ACOG’s Executive Committee. This guideline was published in the same year as the American Cancer Society/American Society for Colposcopy and Cervical Pathology/American Society for Clinical Pathology (ACS/ ASCCP/ ASCP) and the U.S. Federal Preventive Medicine Task Force (USPSTF) guideline updates for cervical cancer screening.
Evidence-Based.
The ACOG reviewed the relevant literature published from January 1990 to March 2012. Priority was given to selecting original research articles while also including reviews, commentaries, and prior guidelines. Due to limited research, the Agency for Healthcare Research and Quality’s modeling studies provided a basis for determining the age at which screening should begin and end and the time interval between screenings. starting screening before age 21 or continuing screening after age 65, or screening less frequently than once every 3 or 5 years, had no significant effect on outcomes for those who received adequate screening.
Two randomized trials demonstrated no difference between traditional and liquid approaches to cervical cytology to identify CIN2+ or CIN3+. Observational studies have demonstrated that HPV testing for CIN2+ and CIN3+ has higher sensitivity but lower specificity than cervical cytology.
The recommendation to start co-testing at age 30 is based on the risk of false-positive cervical cytology results and the known epidemiological characteristics of cervical cancer. Clinical trials have also shown that combined screening has a higher detection rate for cervical adenocarcinoma than cytology alone. Expert opinion guidelines oppose changing the timing of screening schedules based on a history of HPV vaccination.
Pros and cons.
Cervical cancer screening is designed to identify precancerous and invasive cancers. Given the transient and inert nature of HPV infection, the benefits of early detection of cancer must be balanced against the harms of invasive testing required for further follow-up of positive screening results. Starting screening earlier and increasing the frequency of screening can lead to more false-positive results, which means additional testing and treatment is necessary for small changes in cancer risk.
Abnormal screening results lead to more frequent, invasive tests (such as colposcopy or tissue biopsy). The adverse effects of these tests include vaginal bleeding, pain and infection. The psychological impact of a diagnosis of precancerous lesions or cancer (e.g., anxiety and stigma) and the cost of testing are noteworthy.
Discussion.
The ACOG, ACS/ ASCCP/ ASCP, and USPSTF published updates to their cervical cancer screening guidelines in 2012. Different organizations have used data from epidemiologic, modeling, and original studies to determine the appropriate screening method and timing for average-risk asymptomatic women and to balance the benefits of screening with the harms of screening. For cervical cancer screening beginning at age 21 and ending at age 65 (if there are sufficient negative screening results and no history of CIN2+ or greater), the opinions of the guideline editions are consistent.
Studies have shown that separate cytologic screening every 3 years is similar to more frequent screening in reducing cancer risk, and all editions of the guidelines are against annual screening. Combined HPV and cytology screening every 5 years has been shown to have similar rates of cancer cases, screening practices, and deaths in women aged 30-65 years. However, due to the high rate of false positives, this approach is clearly less appropriate for screening women aged 21-29 years. The difference in the guidelines issued by the different organizations is the strength of the recommendation for combined screening.
The ACOG and ACS/ASCCP/ASCP recommend combined screening every 5 years, while the USPSTF recommends this approach as an alternative to a single cytologic test every 3 years.
Areas for future research or ongoing research.
The new version of the recommendations revises the previous version of the guidelines based on new data. HPV testing has emerged as a highly sensitive screening method that better identifies adenocarcinoma compared with cytology, but with a higher risk of false positives. HPV testing is being further integrated into clinical practice and the results of different screening strategies (including those that incorporate HPV testing) need to be tested to determine risk versus harm.
Preliminary studies have also demonstrated high-sensitivity HPV testing without cytology; however, further data and method development are needed before high-sensitivity superiority HPV testing can be adopted as a screening method in practice. Long-term studies of the effectiveness of different methods are needed to adopt appropriate screening methods based on the risk and goals of women at high risk for cervical cancer, and alternative methods for women at low risk to maximize benefit and minimize risk.