HPV testing could be future strategy for primary screening for cervical cancer

Authors of a UK study in this week’s issue of THE LANCET propose a new approach for cervical cancer screening. Testing for the human papilloma virus (HPV)-the main cause of cervical cancer-could be the primary screening tool, with cytology reserved for women who test positive for HPV.

HPV testing (by genetic analysis) of cervical smears is known to be more sensitive than conventional cytology for detecting pre-malignant cervical cells called high-grade cervical intraepithelial neoplasia (CIN2/CIN3); however HPV testing is less specific than cytology (ie. it produces more ‘false-positive’ results). HPV testing as a primary screening approach is only feasible if appropriate management is given to women who are HPV-positive with negative or borderline cytology results.

The HART (HPV in Addition to Routine Testing) study was led by Jack Cuzick and colleagues from Cancer Research UK. Around 11,000 women aged 30-60 years from 161 GP practices in 5 UK regions participated in the study between 1998 and 2001. Women with borderline cytology and women positive for high-risk HPV with negative cytology were randomised to immediate colposcopy (detailed examination of the cervix) or to surveillance by repeat HPV testing, cytology, and colposcopy at 12 months.

HPV testing was more sensitive than borderline or worse cytology (97% compared with 77%) but slightly less specific (93% compared with 96%) for detecting malignant cells. Surveillance at 12 months was as effective as immediate colposcopy for women with minimal abnormalities, i.e., those women with either borderline cytology results (regardless of HPV status) or who were HPV positive but had negative cytology results.

Jack Cuzick comments: “HPV testing could be used for primary screening in women older than 30 years, with cytology used to triage HPV-positive women. HPV-positive women with normal or borderline cytology (about 6% of screened women) could be managed by repeat testing after 12 months. This approach could potentially improve detection rates of CIN2/CIN3 without increasing the colposcopy referral rate.”

In an accompanying Commentary (p 1866), Eduardo Franco from McGill University, Montreal, Canada, concludes: “The HART trial can be viewed as a launching pad for future randomised trials that will assess the duration of protection conferred by a negative HPV result and the efficacy of a Pap-centered triage approach. A paradigm change, if necessary, will represent far more than a technicality. It will mean that cervical cancer screening will shift from a morphology-based approach to one in which the search for a sexually transmitted virus becomes the focus of disease detection. Clients and providers will have to learn to live with the new paradigm, one which places the emphasis of prevention not only on women but on their partners as well. It is about time.”