Study: Co-testing Pap and HPV Finds More Precancer and Cancer than Single Testing

The 2020 Quest Health Trends Study® supports previous research that revealed co-testing for Pap and HPV is more effective in detecting cervical precancer and cancer in women aged 30-65. Harvey W Kaufman, MD, FCAP, senior medical director, and lead of Quest Diagnostics Health Trends® conducted the study with colleagues. The study examined 13.6 million women between 2010 and 2018. It was a heterogenous sample of the population of the United States. Women were co-tested and had a minimum of 1 biopsy before a cervical precancer or cancer diagnosis. Researchers reported 19 million co-testing data points and 625,000 co-tests that were followed by a minimum of 1 biopsy.

Researchers reported 94% of cervical cancers were found with co-testing <12 months to diagnosis, and 22.5% of diagnosed cancers would have remained undiscovered with HPV testing alone.1 In addition, 99.7% of precancers were identified with co-testing, 11% of which would not have been found with HPV testing alone.¹

For cancer outcomes for the 9-year duration of the study period, co-testing HPV and Pap found more cases of cancer: HPV alone identified 72%, Pap alone identified 74%, and co-testing identified 87%, researchers reported.1 The study found that adenocarcinoma rates are rising, and that individual testing of HPV or Pap did not identify 2 times as many women with this cancer as co-testing.¹

Researchers stressed that real-world comparisons confirm the effectiveness of co-testing. “This real-world study is more relevant to drive decisions about cervical cancer screening algorithms than data that includes a microcosm of patients,” Quest said in a press release.

The research confirms several other studies on the subject. A 2018 study that performed a longitudinal, real-world analysis of data examined 186,000 women aged 30-65 in whom co-testing significantly reduced false negative results for cervical pre-cancer and invasive cervical cancer.² This study said that for >12 months, 50% of women would not have had cancer identified with only HPV testing; that number was 24% for Pap only testing. In a 12-month period or longer for cervical intraepithelial neoplasia and adenocarcinoma in situ (CIN3+/AIS), the study found 46% of women would not have been diagnosed with HPV testing alone and 27% would not have been found with Pap alone.2 In addition, the rate of false positives was much lower in women who had undergone co-testing.

Researchers emphasized that co-testing is essential in the press release, which also reported that screening intervals have increased over time. The release said these intervals are patient-age dependent, and include Pap alone every 3 years with co-testing every 5 years or HPV alone testing every 5 years. The release noted that in the US, “cervical cancer screening is opportunistic rather than routine,” and that the guidelines strongly support co-testing in women aged 30-65.

In an interview with Contemporary OB/GYN®, Kaufman emphasized that “co-testing is the most sensitive and best approach to identify cervical cancer. A departure from co-testing will likely lead to more women being diagnosed with cervical cancer and possibly lead to more deaths.” When asked about the next steps to be taken, Kaufman said that models for cervical testing need to consider the rate of the disease’s progression and endeavor to identify women who develop cancer more quickly. “As the interval between screening events increases, so will the likelihood of women whose cervical disease progresses quickly between screening events,” he said. He added that more women are likely to be diagnosed with cancer and more advanced cancer as screening intervals are extended.

Kaufman also noted the need to recognize racial and ethnic disparities. “Black, non-Hispanic women are more likely to develop cervical cancer than White non-Hispanic women. Further, 56% of Black, non-Hispanic women will survive cervical cancer after 5 years compared with 68% of White non-Hispanic women,” he explained. He stressed the importance of cancer screening programs addressing the observed reality of each population. “They should not be based on the average woman, because she may not represent women at higher risk such as Black, non-Hispanic women,” Kaufman said. He also noted that more than 20% of cancer diagnoses are higher in women over 65 because fewer women are having hysterectomies. In addition, he said some younger women have more aggressive cancer. He stressed the need of screening programs to monitor both of these populations.

“Pap is one of the most remarkable tests used to dramatically decrease incidence of a cancer. Great strides forward should not be reversed without careful deliberation that remains missing in the current guideline development process,” Kaufman told Contemporary OB/GYN®. “We are deeply concerned that the haste to embrace guidelines that support primary HPV screening will lead to an increase in cervical cancer deaths, especially among minority and both young and older women.”

References

1. Kaufman HW, Alagia DP, Chen Z, Onisko A, Austin RM. Contributions of liquid-based (papanicolaou) cytology and human papillomavirus testing in cotesting for detection of cervical cancer and precancer in the United States. Am J Clin Pathol. 2020;154(4):510-516. doi:10.1093/ajcp/aqaa074
2. Austin RM, Onisko A, Zhao C. Enhanced detection of cervical cancer and precancer through use of imaged liquid-based cytology in routine cytology and HPV cotesting. Am J Clin Pathol. 2018;150(5):385-392. doi:10.1093/ajcp/aqy114