HPV screening alone best bet for cervical cancer

Among the screening strategies for cervical cancer, stand-alone human papillomavirus (HPV) testing provides a better balance of benefits and harms than co-testing with conventional Papanicolaou (Pap) smear or liquid-based cytology (LBC), as shown in the MARZY cohort study.

“We found similar accuracy of stand-alone HPV testing and LBC co-testing, and superior accuracy of stand-alone HPV compared to Pap-based co-testing. However, adding cytology to HPV as a co-test offers nearly no benefit in detection at the cost of more false positive results and colposcopy referrals,” according to the investigators.

“These results are relevant for countries that offer co-testing, like Germany and the US, and for many other countries globally that are yet to decide on HPV-based screening… [They] support the argument that co-testing, regardless of cytology method, does not outperform stand-alone HPV screening in detection [of cell abnormalities on the cervix],” they added.

MARZY was based on a large population-based sample of women >30 years of age within an opportunistic screening setting and notably poor quality in cytology in Germany. Of the 5,275 women invited for screening with Pap smear, LBC (ThinPrep), and HPV testing (Hybrid Capture 2 [HC2] or PCR), 2,627 (49.8 percent) participated.

The mean age of the women was 47.09 years. Only 27 percent of those aged 30–39 years and 15 percent of ≥60-year-old women attended screening. Meanwhile, about 9 percent of all participants reported to have never undergone screening or did not attend screening at the recommended interval nor within a 5-year period.

As pointed out earlier, neither of the co-testing strategies bested stand-alone HC2 or PCR. For moderate cervical intraepithelial neoplasia (CIN2) or worse (CIN2+), for example, HC2 demonstrated the highest sensitivity (stand-alone, 94.56 percent; co-testing, 98.82 percent), with the stand-alone HC2 test being significantly more sensitive than stand-alone PCR (79 percent) and either of the cytology tests (Pap and LBC, both 47.47 percent; p<0.0001). [Cancer Epidemiol Biomarkers Prev 2020;doi:10.1158/1055-9965.EPI-20-1003]

While HPV co-testing demonstrated higher sensitivities (HC2, 99 percent; PCR, 84 percent), the specificities were lower (92–95 percent) when compared with stand-alone HPV (HC2, 95 percent; PCR, 94 percent) and cytology (97 percent or 99 percent).

Co-testing did not detect more CIN2+ than did stand-alone HPV screening (HC2: relative sensitivity, 1.06, 95 percent confidence interval [CI], 1.00–1.21; PCR: relative sensitivity, 1.07, 95 percent CI, 1.00–1.27). Moreover, relative specificity of Pap co-testing with either HPV test was inferior to stand-alone HPV. LBC co-testing demonstrated similar specificity (both tests: 0.99, 95 percent CI, 0.99–1.00).

Pap co-testing achieved the highest accuracy for detecting precancerous lesion.

“Current arguments for co-testing are based on retrospective results from the US, which have demonstrated marginally lower cumulative incidence of CIN3+ under triennial co-testing compared to HPV stand-alone screening,” the investigators said. “However, the translation of this marginally lower risk by co-testing into real screening practice may not be realized until many tens of thousands of women are screened, particularly with opportunistic screening.” [J Low Genit Tract Dis 2017;21:261-267; J Clin Microbiol 2015;53:2798-2780]

“Screening women aged ≥30 years with sole HPV-based testing should also be considered in the future in order to maximize early detection and to further reduce the incidence of cervical cancer towards elimination,” they added.