Advances in our understanding of the pathogenesis of cervical cancer, new tests for human papillomavirus (HPV), and the development of HPV vaccines in the last decade are transforming the way we screen for cervical cancer.
As a result, screening guidelines are evolving rapidly, requiring clinicians to keep up-to-date with the evidence and rationales supporting the latest guidelines to properly convey best practices to patients.1–3
For example, we must understand why it is safe to extend the screening interval in women at low risk (as recommended in the new guidelines), and we need to be familiar with the options for women who test positive for HPV. Patients and providers may often find such new recommendations frustrating, and patients may feel that they are being denied something necessary by insurers rather than being treated according to scientific evidence.
This article will review the newest screening guidelines and the evidence supporting these recommendations for primary care providers. We will also review the potential role of novel biomarkers, newer HPV tests, and possible future strategies for cervical cancer screening.
WHAT’S NEW IN THE LATEST SCREENING GUIDELINES
Over the years, various organizations have issued separate screening guidelines, sometimes agreeing with each other, sometimes disagreeing.4 Now, for the first time, several of these organizations have developed guidelines collaboratively, and we have consensus in the screening recommendations.
Shortly after the American Congress of Obstetricians and Gynecologists (ACOG) issued its screening guidelines in December 2009,1 the American Cancer Society (ACS), American Society for Colposcopy and Cervical Pathology (ASCCP), and American Society for Clinical Pathology (ASCP) convened an expert panel to review the available evidence and develop a new joint screening guideline. Concurrently, the US Preventive Services Task Force (USPSTF) commissioned a targeted systematic review of the latest evidence.
Both the ACS/ASCCP/ASCP group2 and the USPSTF3 released their new guidelines on March 14, 2012. In November 2012, ACOG issued its latest recommendation on cervical cancer screening.4 The following discussion highlights the consensus recommendations from these organizations (Table 1).
These guidelines apply to the general population only. They do not apply to women at high risk who may require more intensive screening, such as those who have a history of cervical cancer, are immunocompromised (eg, positive for human immunodeficiency virus [HIV]), or were exposed in utero to diethylstilbestrol.
Start screening at age 21
According to the new guidelines, women younger than 21 years should not be screened, regardless of the age at which they start having sex.1–3 This is a change from the 2002 and 2003 ACS recommendations, which said screening should begin 3 years after the onset of vaginal intercourse.5,6
Evidence. The rationale for the recommendation not to screen before age 21 stems from two pieces of evidence:
- Invasive cervical cancer is rare in this age group.7
- Screening can cause harm. For example, unnecessary treatment of preinvasive lesions can lead to long-term complications such as cervical stenosis, preterm delivery, and preterm premature rupture of membranes.8,9
Additionally, one study found that screening before age 21 has little or no impact on the incidence of invasive cervical cancer.10
Longer screening intervals
The 2012 ACS/ASCCP/ASCP guidelines2 and the latest ACOG guidelines4 lengthen the interval between cytology (Papanicolaou) testing to every 3 years in women age 21 to 29. Previous recommendations from these groups were to screen every 2 years, and the USPSTF first recommended the 3-year interval in 2003.11
For women age 30 to 65, the ACS/ASCCP/ASCP, ACOG, and the USPSTF now recommend screening every 5 years if the patient’s results on combined cytology and HPV testing are negative. However, cytologic testing alone every 3 years is also acceptable.2–4
Evidence. The evidence supporting a 3-year screening interval in women age 21 to 29 is primarily from modeling studies—no randomized clinical trial has been done. These studies found no significant difference in outcomes with a 2-year vs a 3-year screening interval.12,13 In particular, the predicted lifetime risk of cervical cancer in women screened every 3 years was 5 to 8 new cases of cancer per 1,000 women, compared with 4 to 6 cases per 1,000 women screened every 2 years.14
Similarly, screening women younger than age 30 at 2-year or 3-year intervals carried the same predicted lifetime risk of death from cervical cancer of 0.05 per 1,000 women, yet women screened every 2 years underwent 40% more colposcopies than those screened every 3 years.2 Therefore, screening every 3 years offers the best balance of benefits and risks in this age group.
Adding HPV testing to cytologic testing increases the sensitivity of screening—thus the recommendation to lengthen the screening interval to every 5 years in women age 30 to 65 who are at low risk and who have negative results on both tests. (Previously, the interval was 3 years.)
Specifically, adding HPV testing improves the sensitivity of screening for cervical intraepithelial neoplasia grade 3 (CIN3), so that, in subsequent rounds of screening, fewer cases of CIN3 or worse (CIN3+) or cancer are detected.15–17 The longer diagnostic lead time with combined testing is associated with a lower risk of CIN3+ or cancer following a double-negative test result than screening with cytology alone at shorter intervals. Combined testing at 5-year intervals is associated with a similar or lower cancer risk than cytology-alone screening at 3-year intervals.9
Moreover, modeling studies have shown that combined testing of women age 30 and older at 5-year intervals leads to fewer colposcopies and a similar or lower cancer risk than with cytology screening at 3-year intervals.18,19