Cervical cancer screening: Less testing, smarter testing

NEW STANDARD OF CARE: THE LATEST SCREENING GUIDELINES

Until the mid-1990s, the strategy for cervical cancer screening had remained largely unchanged for many years. Since then, several advances have prompted changes in the standard of care.

1996—The US Food and Drug Administration (FDA) approved liquid-based Thin-Prep for cervical cancer screening, which improved specimen adequacy and reduced ambiguous interpretations compared with the original slide-based method of collection.⁴⁹

2001—The Bethesda terminology for reporting cervical cytology results was updated. First proposed in 1988 to replace the original Papanicolaou system and revised in 1991, this standardized terminology enabled better clinical decision-making.⁵⁰

2001—The FDA approved HPV testing for women with ASC-US. This provided a better triage strategy for deciding which women need colposcopy to exclude true intraepithelial lesions. Following the FDA approval, the clinical effectiveness of HPV testing in women with ASC-US was validated by a large randomized clinical trial—the ALTS.⁵¹

2003—The FDA approved HPV testing in conjunction with Pap testing for women age 30 or older in routine primary screening.⁵²

Guidelines available

Based on these new developments in technology and reporting terminology, and the incorporation of HPV testing, several organizations issued guidelines.

The American Society for Colposcopy and Cervical Pathology published a consensus guideline on management of abnormal cervical cytology in 2001 and revised it in 2006.⁵³

The American Cancer Society issued its guideline for cervical cancer screening in 2002.⁵⁴

The US Preventive Services Task Force published its screening guidelines in 2003.⁵⁵

The American College of Obstetricians and Gynecologists (ACOG) also made new recommendations in 2003 and updated them in December 2009.¹

Start screening at age 21

Cervical cancer screening should begin at age 21 regardless of the age of onset of vaginal intercourse, according to the 2009 ACOG guidelines.¹ This represents a change from previous recommendations from ACOG, the American Cancer Society, and the US Preventive Services Task Force, which were to start screening within 3 years of the onset of vaginal intercourse.

Rationale. This latest recommendation is based on the high rates of clearance of HPV infection and of spontaneous dysplasia regression and the low incidence of cervical cancer in younger women.^57,58 HPV infections are common in young women who have had vaginal intercourse. However, most such HPV infections are cleared by the immune system within 1 to 2 years without causing cervical dysplasia.^11,12 Invasive cervical cancer in women younger than 21 years is very rare. The annual incidence is only one to two cases per 1 million women ages 15 to 19.^2,55

Another reason for not screening before age 21 is that a positive test result may lead to unnecessary anxiety and potentially harmful evaluations and procedures.

Screening intervals extended

The 2009 ACOG guidelines lengthen the cervical cancer screening interval to every 2 years in women under age 30.¹ (The 2003 ACOG guidelines said to screen every year.)

For women age 30 and older, the 2009 ACOG guidelines recommend extending the interval to every 3 years when combined Pap and HPV testing are negative (changed from every 2 to 3 years).¹

Rationale. Studies have shown little advantage in screening every year in women under the age of 30, with no higher risk of cervical cancer in women screened at a 2- to 3-year interval.^59–62 The absolute risk of cervical cancer in a well-screened population is very low.⁶³ Moreover, the absolute number of cervical cancer cases in women age 30 to 64 years screened at 3-year intervals is only four per 100,000 women.⁶⁴

HPV-plus-Pap testing for women over 30

Based on convincing evidence of the high sensitivity and the high negative predictive value of HPV testing, since 2003 ACOG had recommended HPV-plus-Pap testing in women over age 30. Its 2009 guidelines upgraded this recommendation to level A, ie, the highest grade, based on good and consistent scientific evidence.¹ (Previously the recommendation was level B.)

The American Cancer Society also recommends combined HPV and Pap testing as the optimal screening approach in women age 30 or older, with the subsequent screening interval 3 years if both tests are negative. It also endorses Pap testing alone every 2 to 3 years as an alternative screening strategy in this age group.

The US Preventive Services Task Force recommends Pap testing every 3 years in women age 30 or older, and it does not recommend for or against HPV testing. However, neither the US Preventive Services Task Force nor the American Cancer Society has updated its guidelines in 8 years.

Rationale. Women who undergo HPV-plus-Pap testing and who test negative on both are at very low risk of developing CIN2 or CIN3 during the next 4 to 6 years. The risk is much lower than that for women who have a sole negative Pap test result.^39,40 Because of this extremely high negative predictive value, women age 30 and older who had negative results on both Pap and HPV testing should be screened no more often than every 3 years.

We believe that the HPV-plus-Pap testing strategy recommended by the 2009 ACOG guidelines for women age 30 and older is the most effective screening approach. This strategy takes advantage of the high sensitivity and high negative predictive value of HPV testing, as well as the high specificity of Pap testing. It achieves almost 100% clinical sensitivity in detecting cervical dysplasia.⁴⁶