Overview of the European and North American studies on HPV testing in primary cervical cancer screening

Abstract

Several studies suggest that HPV testing is more sensitive than cytology in primary cervical screening. These studies had different designs and were reported in different ways. Individual patient data were collected for all European and North American studies in which cytology was routinely performed and HPV testing was included as an additional parallel test. More than 60,000 women were included. The sensitivity and specificity of HPV testing were compared with routine cytology, both overall and for ages <35, 35-49 and 501. The age-specific prevalence of high risk HPV (hr-HPV) was also analysed. HPV testing was substantially more sensitive in detecting CIN21 than cytology (96.1% vs. 53.0%) but less specific (90.7% vs. 96.3%). The sensitivity of HPV testing was similar in all studies carried out in different areas of Europe and North America, whereas the sensitivity of cytology was highly variable. HPV sensitivity was uniformly high at all ages, whereas the sensitivity of cytology was substantially better in women over the age of 50 than in younger women (79.3% vs. 59.6%). The specificity of both tests increased with age. Positivity rates for HPV testing in women without high-grade CIN were region dependent. These results support the use of HPV testing as the sole primary screening test, with cytology reserved for women who test HPV positive. Large demonstration projects are needed to fully evaluate this strategy. ' 2006 Wiley-Liss, Inc.Key words: HPV testing; cervical screening; sensitivity; specificity; primary screening Currently in Europe and North America, cervical cancer screening is based on exfoliative cytology performed at intervals ranging between 1 and 5 years. Although there has been a marked reduction in incidence and mortality rates of squamous cell carcinoma of the cervix in countries with established cytology screening programmes, 1-3 Sasieni et al. (1996) reported that 47% of women in the UK who developed stage 1B1 or worse invasive cervical cancer before the age of 70 had had an adequate previous screening history. 2 The weaknesses in cytology are 3-fold. First, results are dependent on the high quality sample being collected during examination. Second, the test requires the identification of morphological changes within cells, whose interpretation is highly subjective. Last, this method of screening is particularly repetitive, which can lead to a greater number of interpretive errors. False negative cytology has major medical, economic and legal implications, and this is reflected in high malpractice litigation costs in the US associated with misreading cervical smears.Interest in the use of HPV testing as a screening test is based on the finding that HPV DNA is present in almost all cervical cancers, 4 and the availability of easily performed tests, which have demonstrated higher sensitivity for high grade CIN (CIN21) than that achieved by cytology in several studies. This higher sensitivity offers several potential advantages, including reduced cancer rates and longer screening intervals, ...

Age-dependent prevalence of 14 high-risk HPV types in the Netherlands: implications for prophylactic vaccination and screening

“…However, comparison of the HPV prevalence in opportunistically screened women aged 27 or 28 years to screening-eligible women aged 29 or 30 years did not show a trend shift in HPV prevalence (data not shown). Moreover, we observed an overall hrHPV prevalence of 21% in the age group 18 -24 years, which is consistent with the international literature (Winer et al, 2003;Manhart et al, 2006;Cuzick et al, 2006).…”

“…A related discussion concerns the choice of the primary screening instrument. Metaanalyses have shown that, HPV DNA testing has a higher sensitivity than cytology (Arbyn et al, 2006;Cuzick et al, 2006) and may be implemented in cervical screening in the future. In this study, we have shown that on removing HPV16/18 infections, the positive predictive values of HPV testing and cytology show similar decreases.…”

HPV and cervical cancer: screening or vaccination?

“…Second, over 15 studies have consistently shown that the use of HPV DNA tests as the primary screening method is significantly more sensitive than cytology-based screening, either conventional or liquid based (International Agency for Research on Cancer, 2005;Cuzick et al, 2006a;Ronco et al, 2006;Mayrand et al, 2007). The summary gain in sensitivity is in the range of 25 -35%, and the reasons for it are clearly understood: (a) the presence of HPV DNA is a necessary prerequisite for cervical intraepithelial neoplasia (CIN) 2 þ ; (b) the sensitivity of HPV tests is consistently high (490%) across different laboratories, with an average level of sophistication in technology; (c) the detection of HPV DNA is independent of the limitations of any human eye observation, as it is the case with colposcopy, cytology and histology; and (d) HPV being often a field infection, the detection of the viral DNA is largely independent of the sampling ability to the point that selfsampling is able to detect HPV DNA at a similar level to that of the professionally collected cervical sample.…”

Effectiveness of a two‐stage strategy with HPV testing followed by visual inspection with acetic acid for cervical cancer screening in a low‐income setting

“…Since it does not directly test for cervical cancer but for HPV infection, a negative test result holds a high probability for the patient not to develop cervical cancer within 5-10 years following completion of the test, whereas a positive result only indicates the presence of an essential risk factor. 9 HPV infection is a very common condition in young women with prevalence over 25% in those aged younger than 30 years in Cameroon. 14 Studies carried out in other African countries found a PPV for HPV testing to be lower than 30%.…”