PCR-based high-risk HPV test in cervical cancer screening gives objective risk assessment of women with cytomorphologically normal cervical smears

Abstract

Cemcalsancer screening programmes using cytomorphologi-cal criteria could be more efficient if the screening included objective individual risk factors for women with normal cytol-ogy, such as a test for high-risk human papillomavirus (HPV). The value of a PCR-based test for high-risk HPV types was studied in a cohort of 1622 women presenting in a routine triannual population-based screening programme. Women were included in the study when they had no previous history of cervical dysplasia; and their initial Pap smear was read as normal (Pap I or 2). The mean age of the women was 42 years (range 34-54 years) and mean follow-up time was 40 months (range 5-73 months). Women were referred for colpoxopically directed biopsies if they had had 2 successive cervical smears read as Pap 3a (mild to moderate dyskaryosis) or one read as ?Pap 3b (severe dyskaryosis). Women with histologically confirmed cervical intraepithelial neoplasia grade 111 (CIN 111) were considered positive cases. All women were tested for 14 high-risk HPV genotypes. Of the 86 high-risk HPV-positive women, 6 developed CIN 111, whereas only I of the 1536 HPV-negative women did. The women with normal Pap smears containing high-risk HPV genotypes were I 16 times (95% CI, 13-990) more at risk of developing CIN 111, in contrast to women without high-risk HPV. These results support the view that the interval between successive smears in cervical-cancer screening can be increased considerably for women with cyto-morphologically normal and high-risk HPV-negative cervical smears as determined by PCR. c 1996 Wiley-Liss, Inc. Detection of cytomorphologically abnormal cells in smears of the uterine cervix is used in cervical-cancer screening programmes to identify women with cervical cancer and cervical intraepithelial neoplasia (CIN). However, cytomorpho-logical examination has major drawbacks (Koss, 1989). The percentage of false-negative cervical smears varies from 15 to SO%, while the number of false-positive smears is about 10% (Coppleson and Brown, 1974). This means that the sensitivity of cytology for cervical cancer and CIN is quite low (5 0 4 5 %) and the specificity is about 90%. The lack of sensitivity is compensated by repeating the procedure after a fairly short time interval, up to 3 years, depending on the result of the Pap-smear (IARC Working Group, 1986). There is strong epidemiological and molecular biological evidence that infection with high-risk human papillomaviruses (HPV) plays an important role in the development of cervical cancer (IARC Working Group, 1995). In addition, the relevant high-risk HPV types can now be detected in one PCR reaction (Wal-boomers et al., 1994). Thus, the question has been raised whether cervical-cancer screening may become more efficient when testing for high-risk HPV DNA is included in thc screening procedure (Meijer et al., 1992). In this study we evaluate whether the presence of high-risk HPV types in cytomorphologically normal (Pap 1 or 2) cervical smears is predictive for development of CIN 111 among women ...

High-risk human papillomavirus clearance in pregnant women: trends for lower clearance during pregnancy with a catch-up postpartum

“…Keywords: human papillomavirus; pregnancy; follow-up study; natural history; prevalence Several epidemiological and biological studies have established the important role of infection with high-risk types of human papilloma virus (HPV) for development of cervical cancer and its precursor lesions. In women with or without abnormal cervical smears a positive high-risk HPV test result indicates an increased risk for development of high grade cervical lesions (Ho et al, 1995;Remmink et al, 1995;Rozendaal et al, 1996Rozendaal et al, , 2000Nobbenhuis et al, 1999). Moreover, in nearly all cervical cancers high-risk HPV types have been detected .…”

Extended duration of the detectable stage by adding HPV test in cervical cancer screening

“…The confidence interval around the relative risk found by Rozendaal et al (1996) was large (from 27 to 1600). The upperbound of the confidence interval results in an HPV infection duration of 5.5 years.…”

“…The study population, and screening and follow-up results are described in Rozendaal et al (1996Rozendaal et al ( , 2000. Briefly, the smears obtained during routine screening from 1988 to 1991, from a cohort of 2250 women aged 34 -54 years, who were either normal or who showed borderline nuclear changes were tested for a highrisk HPV.…”

“…To estimate preclinical duration and sensitivity, longitudinal studies on the association between HPV infection and the development of neoplasias are necessary. Several large longitudinal screening studies have started, but no longterm results have been reported yet, although smaller longitudinal studies have been published (Rozendaal et al, 1996(Rozendaal et al, , 2000Ho et al, 1998;Liaw et al, 1999). These studies differ with respect to HPV test used, age range of women, study design, and cytological or histological endpoint, which complicates the comparison and interpretation of these results.…”

Natural history and screening model for high‐risk human papillomavirus infection, neoplasia and cervical cancer in the Netherlands

“…[5][6][7][8][9] Combined screening (hrHPV and cytology) leads to an earlier detection of women who are at risk for developing high-grade lesions 10 and has a higher sensitivity for the detection of high-grade lesions. 11 However, hrHPV testing also induces extra screening costs so that the determination of the optimal screening scenario involves an elaborate cost-effectiveness analysis.…”