Triage of women with minor cervical lesions: data suggesting a "test and treat" approach for HPV E6/E7 mRNA testing

Abstract

Background: Human papillomavirus (HPV) testing is included in the cervical cancer screening program in the triage of women with equivocal (ASC-US) or low-grade (LSIL) cytological lesions. These women have an increased risk for developing high grade dysplasia and cancer (CIN2+) compared to women with normal cytology. However, in order to avoid unnecessary follow-up, as well as overtreatment, a high positive predictive value (PPV) of the triage test is important.

Methodology/principal findings: The HPV test PreTect HPV-Proofer, detecting E6/E7 mRNA from the HPV types 16, 18, 31, 33 and 45, is used as triage test together with repeat cytology. PPV data for HPV E6/E7 mRNA testing during the period from January 2006 up to June 2009 are reported. In total, 406 of 2099 women (19.3%) had a positive HPV test result. Of the women with a positive test result and with a histological diagnosis (n = 347), 243 women had histological high-grade dysplasia or cancer (CIN2+), giving a PPV of 70.0% (95% confidence interval [CI], 65.2%-74.8%). For HPV 16 or HPV 33 positive women above 40 years of age, the PPV was 83.7% (95% CI, 73.3%-94.0%) and 84.6% (95% CI, 65.0%-100.0%) respectively. The PPV of test positive women with HSIL cytology was 94.2% (95% CI, 88.7%-99.7%).

Conclusions: When the result in triage is HPV mRNA positive, our data suggest direct treatment for women above 40 years of age or for women with a concurrent cytological HSIL diagnosis, contributing to better clinical safety for these women. In addition, by decreasing the time to treatment, thereby reducing the number of recalls, the patient management algorithm will be considerably improved, in turn reducing follow-up costs as well as unnecessary psychological stress among patients.

Figure 1. Flow chart showing the guidelines for HPV E6/E7 mRNA testing.

Women with ASC-US or LSIL at triage and with a positive HPV result are referred to colposcopy and biopsy; if the HPV test is negative, the woman is referred to a third Pap-smear after one year. Women with normal cytology and a positive HPV mRNA result at triage are recommended to have a third Pap-smear and a new HPV mRNA test after 6 months; women with a persistent HPV mRNA result are referred to colposcopy and biopsy. Women with ASC-H and HSIL at triage are referred directly to histological investigation regardless of HPV status.