For decades after the 1941 publication of “The Diagnostic Value of Vaginal Smears in Carcinoma of the Uterus” by Papanicolaou and Traut,¹ the Papanicolaou (Pap) smear was the test of choice for cervical cancer screening. Recently, there have been attempts to improve the sensitivity of this common screening test, which is approximately 55 percent for high-grade lesions.² This has led to the development of liquid-based cytology and refinements in human papillo-mavirus (HPV) testing. In this issue of American Family Physician, Apgar and colleagues review the 2006 revised American Society for Colposcopy and Cervical Pathology consensus guidelines for cervical cancer screening and management of abnormal Pap test findings.³ It is important for physicians to remain informed about new guidelines and ongoing research, which have changed the techniques we use for cervical cancer screening and the patient populations we screen.

Conventional Pap testing uses a glass slide sprayed with a fixative. A newer, alternative technique uses liquid-based cytology. The U.S. Food and Drug Administration granted approval for two commercial liquid-based systems on the premise that they increase detection of squamous intraepithelial lesions and decrease the number of unsatisfactory Pap tests compared with the conventional Pap test.^4,5 This has led to more than 80 percent of U.S. obstetrician-gynecologists switching to the liquid-based collection technique.⁶ However, recent evidence, including a large trial of more than 45,000 women randomized to liquid-based or conventional cytology, and a meta-analysis of both techniques, revealed that liquid-based technology does not lead to greater detection of high-grade cervical intraepithelial neoplasia and increases the number of false-positive results.^2,7 False-positive results lead to unnecessary colposcopy and, in some cases, excisional or ablative therapy, which is particularly concerning in younger patients. Despite these limitations, most U.S. laboratories have converted to liquid-based screening, which allows physicians to test for HPV and certain sexually transmitted infections while performing the Pap test.

The use of HPV testing has dramatically changed the technique of cervical cancer screening. HPV is an almost ubiquitous sexually transmitted infection, particularly in girls and women 15 to 24 years of age within a few years of sexual debut, and HPV serotypes are found in almost 98 percent of cervical cancer specimens.⁸ Strategies involve testing for these high-risk serotypes (e.g., types 16 and 18) to help in the triage of patients with oncogenic HPV types to colposcopy and treatment.

Reflex screening is now common for patients with atypical squamous cells of undetermined significance (ASC-US). New guidelines have expanded the role of high-risk HPV testing. For example, new evidence suggests that the sensitivity of cervical cancer screening is improved by combining HPV and Pap tests for women older than 30 years.^9,10 Convincing these women and their physicians that it is acceptable to extend cervical cancer screening to every three years after a negative HPV test result and normal cytology findings will be an important challenge to decrease health care costs.¹ Recent studies modeling the cost-effectiveness of various cervical cancer screening programs suggest that using the new guidelines will be more cost-effective than the previous, annual Pap testing system.¹¹ While we await further evidence confirming cost-effectiveness of this combination, the Pap test alone is still an option for women older than 30 years.

In addition to changes in how to screen for cervical cancer, new guidelines attempt to avoid overscreening and overtreatment in adolescents. HPV infection is common in girls and women 15 to 24 years of age, but cervical cancer in this age group is rare. In contrast to prior belief, we now know that most girls and young women will spontaneously clear about 90 percent of HPV infections within two years.¹² For this reason, newer recommendations state that Pap testing should begin at 21 years of age, or three years after sexual debut.¹⁰ Further, the new guidelines suggest avoiding overtreatment by extending follow-up screening to every 12 months in patients with ASC-US and low-grade squamous intraepithelial lesion for up to two years before colposcopy, because these abnormalities are common but usually transitory in adolescents.¹⁰ Also, the current focus is on treating persistent high-grade lesions, but not less severe abnormalities, to prevent complications from excisional procedures. This will require education of physicians, patients, and worried parents who are used to more aggressive follow-up and treatment protocols.

What is the future of cervical cancer screening? With the goals of cost-containment, patient convenience, and prevention of overtreatment, future research should evaluate whether HPV testing alone can replace cytology screening, if repeat Pap or HPV screening can be extended further than three years in select patients, and if screening in underserved areas with limited resources might be accomplished by beginning screening when women are closer to 30 years of age, when the risk of cervical cancer rises relative to that in younger women.