New Cervical Cancer Screening Guidelines May Increase the Risk for Invasive Adenocarcinoma in Young Patients

March 2016 Vol 7, No 2
Christine Erickson

Invasive cervical cancer is curable when diagnosed and treated early, and Papanicolaou (Pap) test screening is an effective means of reducing the incidence and mortality of this disease. The diagnosis of cervical lesions depends on frequent and consistent Pap test screenings, and cure rates depend on effective screening, diagnosis, and management.

However, cervical cancer screening guidelines have changed often in the past 50 years. Notably, revised US guidelines were published in 2012 by the American Cancer Society (ACS), American Society for Colposcopy and Cervical Pathology (ASCCP), American Society for Clinical Pathology (ASCP), and the US Preventive Services Task Force (USPSTF), which included delaying screening until age 21 years, screening every 3 years from age 21 to 29 years, and the option of extending the screening interval to every 5 years for women aged 30 to 65 years.

In addition, abnormal Pap test results management guidelines published in March 2013 by the ASCCP and in December 2013 by the American Congress of Obstetricians and Gynecologists recommended less invasive treatment strategies for women with preinvasive disease aged 21 to 24 years. In their study, Caroline Nitschmann, MD, Department of Obstetrics and Gynecology, Division of Gynecologic Surgery, Mayo Clinic, Rochester, MN, and colleagues reviewed cases of invasive cervical cancer to examine how the updated Pap test screening guidelines affect the detection of invasive cervical cancer, particularly among women aged <30 years.

Pap Test Screening Tool

This retrospective cohort study was conducted at Brigham and Women’s Hospital, Boston, MA, and included patients who were diagnosed with invasive squamous-cell carcinoma (ISCC) and invasive adenocarcinoma (IAC) of the cervix between 2002 and 2012. The patients were categorized by age; group 1 included patients aged <30 years, and group 2 included patients aged ≥30 years. According to the study authors, this categorization was selected to resemble the updated guideline recommendations, which rely solely on Pap tests for screening in women aged <30 years. The Pap test screening interval was defined as the time from the last normal Pap test until the time of invasive cervical cancer diagnosis. Although 288 patients with invasive cervical cancer were identified, only 109 of them had adequate information on their screening histories. Thus, the 179 patients with incomplete Pap test histories were excluded from the study.

IAC was diagnosed in 37 (33.94%) patients, and ISCC was diagnosed in 64 (58.72%) patients. The remaining 8 patients were diagnosed with other types of cervical cancers. Thirteen patients were aged <30 years, and 96 patients were aged ≥30 years. The mean time from normal Pap test to IAC diagnosis was 15 months in patients aged <30 years, compared with 56 months in patients aged ≥30 (P <.001). The mean time from normal Pap to ISCC diagnosis was 38 months in patients aged <30 years, and 82 months in patients aged ≥30 years (P = .018).

Screening Guidelines

Although the Pap test screening guidelines have changed several times, the update published in 2012 by the ACS, ASCCP, ASCP, and USPSTF includes the most relaxed screening recommendations to date. A review of the Surveillance, Epidemiology, and End Results Program database from 2004 to 2008 showed that approximately 14% of invasive cervical cancers in the United States were diagnosed in patients aged 20 to 34 years. Of the patients diagnosed in this age-group, >50% were diagnosed when they were aged ≤30 years, with the majority of lesions being adenocarcinoma.

Therefore, the study authors confirmed that the new screening guidelines are not likely to miss many cancers in women aged ≥30 years. However, they stated that women aged <30 years who are screened and evaluated at greater intervals may experience an increase in invasive cancers, particularly of adenocarcinoma histology.

Over the past few decades, the incidence of invasive cervical adenocarcinoma has dramatically increased, particularly in younger women. Their increased exposure to risk factors that stimulate glandular neoplasia may explain this upward trend. These risk factors include endogenous (eg, obesity) and exogenous (eg, hormonal contraception) estrogens, and increased prevalence of adenocarcinoma-related human papillomavirus types 16 and 18. Although evidence suggests that Pap test screening for precancerous lesions of squamous histology reduces invasive cancer, glandular lesion screenings are less effective. This is problematic for patients aged <30 years, because most diagnosed, invasive cervical cancers are of glandular histology. Although these challenges exist with the use of Pap test screenings for glandular lesions, this is currently the standard of care for this age-group.

In Dr Nitschmann and colleagues’ study, an abnormal Pap test initiated the workup of cervical disease in approximately 50% of patients aged <30 years. All other patients were symptomatic at the time of presentation, or diagnosed incidentally. In patients aged <30 years, the mean Pap test interval for IAC was less than the recommended 3-year screening gap.

How Did the Pap Test Impact Patients?

The mean Pap test interval for ISCC was approximately 3 years, which is a significant finding in relation to the updated recommended screening guidelines, according to the study authors. With the prior guidelines, patients were screened earlier and more frequently. Based on the data collected, Dr Nitschmann and colleagues assert that patients in group 1 who follow the new screening guidelines have the potential to develop IAC or ISCC before their next Pap test.

These findings also indicate that the current screening guidelines may not correctly detect a large proportion of adenocarcinoma in situ lesions or IAC. Delaying the onset of screening, not evaluating minor Pap test result abnormalities, or delaying treatment of more significant Pap test result abnormalities in women with no screening history as suggested by national guidelines may increase the incidence of IAC in women aged <30 years.

“Based on our data, we agree with current guidelines suggesting screening starting at age 21,” stated Dr Nitschmann and colleagues. “Two patients in this study were diagnosed at ≤21 years of age. Both presented with atypical histological diagnosis (neuroendocrine tumor and adenocarcinoma with clear cell features) and presented with a bleeding cervical mass. One can argue that the traditional Pap test is not helpful in the detection of rare lesions and that these patients presented symptomatically.” Based on the Pap timeline results of their study, the authors also agreed with the current guidelines that suggest screening every 3 years in low-risk patients aged ≥30 years.

Ultimately, this small, retrospective study showed that the updated Pap test screening guidelines would not have missed invasive cancer among screened women aged ≥30 years. However, between the recommended screening intervals, patients aged 21 to 29 years may be at increased risk for developing IAC of the cervix. “Despite our findings, further investigations are needed to determine the true clinical significance of the change in Pap test screening guidelines,” Dr Nitschmann and colleagues concluded. “With improved [electronic medical record], larger and more complete studies can provide more definitive data. Future research should be geared toward the impact of the new screening guidelines and Pap tests on the diagnosis of invasive cervical cancer in this age group.”


  • Nitschmann C, May T, Mirkovic J, Feldman S. Screening history among women with invasive cervical cancer in an academic medical center: will we miss cancers following updated guidelines? J Womens Health (Larchmt). 2016 Feb 9. Epub ahead of print.
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Last modified: January 18, 2021

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