HPV testing may replace Pap smears for primary screening

Journal of Family Practice, April, 2004

Cuzick J, Szarewski A, Cubie H, et al. Management of women who test positive for high-risk types of human papillomavirus: the HART study. Lancet 2003; 362:1871-1876.

* CLINICAL QUESTION

Can human papillomavirus testing replace Papanicolaou tests as the primary means of screening for cervical cancer?

* BOTTOM LINE

Using human papillomavirus (HPV) testing is likely to replace Papanicolaou (Pap) testing for primary screening for cervical cancer for a variety of reasons--detection of the etiologic factor should predate the development of disease; urine testing for HPV may remove patient barriers to screening; and reduced interpretation error. This study can't really provide the kind of data to support this, however. It is even more likely that vaccination against HPV may render both these technologies obsolete. (LOE=2b)

* STUDY DESIGN

Randomized controlled trial (nonblinded)

* SETTING

Outpatient (primary care)

* SYNOPSIS

In this multicenter screening study, 11,085 women aged 30 to 60 years were recruited from 161 family practices in the United Kingdom. To be eligible, the women could not have had an abnormal Pap result in the preceding 3 years and could never have been treated for cervical intraepithelial neoplasia (CIN). Women had a standard Pap test using an extended-tip Ayre's spatula and a sample was placed into transport medium. Women with mild dyskaryosis or worse were referred for colposcopy.

A total of 825 women (8%) showed minimal abnormalities (borderline cytology, or positive high-risk HPV test results and negative cytology) and were randomized to immediate colposcopy or surveillance by HPV testing and cytology at 6 and 12 months. Women in the surveillance group were referred for colposcopy at 6 months if the cytology result progressed to mild dyskaryosis or worse. In all other cases the women were invited for colposcopy and repeat testing at 12 months. HPV testing was more sensitive than abnormal Pap results (97% vs 77%; P=.002) at detecting CIN 2 or worse, but it was less specific (93% vs 96%; P<.0001).

Among the 825 randomized women, immediate colposcopy and surveillance were comparable: 45% of the surveillance women tested positive for HPV at baseline, had negative cytology, and 35% with borderline cytology were HPV negative at 6 to 12 months. None had CIN 2 or worse.

Technically speaking, this is not a trial comparing screening modalities, but rather a trial of different modes of follow-up. Since we don't have outcomes data, and since cervical cancer is relatively rare and tends to be slow-growing, these data need confirmation in larger, longer, more rigorous trials.

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Ximelagatran       Exantra