Cotesting Unlikely to Detect More Cervical Cancers Than HPV Testing Alone

Mark Schiffman, MD

Use of both a Pap smear and an HPV test did not identify more cervical cancers than HPV testing alone, according to results from a study of more than 1.2 million women screened since 2003.

The Pap test detected only a small percentage of precancers (3.5%) and cancers (5.9%) missed on the HPV test. Investigators observed that these cancers were more likely to be regional or distant stage.

Given the relative rarity of cervical cancer—the CDC says roughly 12,000 women are diagnosed annually—investigators concluded that adding the Pap test to HPV screening translated to earlier detection of at most 5 cases per million women per year. Cotesting is “unlikely to detect cancer cases that wouldn't be found using HPV testing alone.”

“The choice between the two strategies and the screening interval chosen, whether three years or five years or more, depends on societal judgments (eg, cancer prevention benefits vs resource allocation) and not scientific facts,” first author Mark Schiffman, MD, division of cancer epidemiology and genetics, National Cancer Institute, et al wrote. “Nevertheless, even using cotesting at three-year intervals (the most aggressive strategy in common use), cervical cancer continues to occur rarely (albeit typically at a curable stage). Excessive screening in an attempt to prevent every case could have minimal cancer prevention benefits while increasing the harms of screening.”

HPV testing is more sensitive than the Pap test for detecting precancer. The HPV test captures the known cancer-causing viruses, but some gynecologists conduct cotesting due to reports of rare HPV-negative, Pap-test—positive cancers, even though using both tests is more expensive.

Investigators quantified the detection of cervical precancer and cancer by cotesting compared with HPV testing alone at Kaiser Permanente, where 1,208,710 women have undergone cervical cotesting every 3 years since 2003. Investigators reviewed screening histories preceding cervical cancers in 623 women and precancers in 5369 women to assess the relative contributions of the Pap test and HPV test components in identifying patients.

Overall, prediagnostic HPV testing (76.7%) was more clinically sensitive than cytology (76.7% vs 59.1%; P <.001 for paired comparison). About 82% of all prediagnostic cotests were positive by HPV and/or cytology. Stratified by histopathology, the differences in positivity between HPV and cytology were smaller for squamous cell carcinoma (75.0% vs 69.6%; P = .03) than for adenocarcinoma (79.0% vs 45.4%; P <.001).

Among those with cancer, women diagnosed with microinvasive cancer tended to be younger than women with other cancers (40 vs 57 years). The median age for women diagnosed with squamous cell carcinomas or adenocarcinomas was 47 years. Women diagnosed with precancer had a median age of 38 years. Investigators noted that this analysis excluded women younger than age 30, elevating the average age of patients with precancer.

HPV testing identified more women subsequently diagnosed with cancer and precancer than the Pap test. Overall, prediagnostic HPV testing was more likely to be positive than cytology (83.8% vs 61.9%; P <.001). Almost nine in 10 prediagnostic cotests (87.3%) were positive by HPV and/or cytology. HPV testing was more likely to be positive than cytology prior to both cervical intraepithelial neoplasia grade 3 (83.9% vs 62.8%; P <.001) and adenocarcinoma in situ (82.2% vs 53.2%; P <.001).

Cotests done within 12 months of diagnosis were more likely to be HPV and/or cytology positive than cotests done ≥12 months before the diagnosis. HPV was statistically significantly more likely to be positive than cytology less than 12 months prior to a precancer diagnosis (96.2% vs 89.8%; P <.001) but not immediately prior to a cancer diagnosis (89.2% vs 86.3%; P = .1).

At ≥12 months, HPV was statistically significantly more likely to be positive than cytology for both a precancer diagnosis (70.6% vs 32.4%; P <.001) and a cancer diagnosis (62.8% vs 28.7%; P <.001).

Schiffman M, Kinney WK, Cheung LC, et al. Relative performance of HPV and cytology components of cotesting in cervical screening [published online November 14, 2017]. J Natl Cancer Inst. doi: 10.1093/jnci/djx225.