Objective-To assess the relation between two risk factors for cervical neoplasia: smoking and infection with oncogenic human papillomavirus. It

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We surveyed cervical intraepithelial neoplasia (CIN) to quantify the proliferation rate and the presence of normal and atypical mitotic figures. In the cervical tissue specimens of 127 women with CIN, the area with the highest cell proliferation was identified and, at that site, the proliferation rate was assessed by calculating the mitotic index (MI). Lesions with an MI < 2 were not considered further. In the area with the highest proliferation rate, 228 mitoses were classified into one of the following groups: normal mitotic figures (NMFs), lag-type mitoses (OLTMs) comprising three group metaphases (3GMs), two group metaphases (2GMs) and other lag-type mitoses (LTMs), multipolar mitoses (MPMs) comprising tripolar mitoses (3PMs) and quadripolar mitoses (4PMs), and other atypical mitotic figures (OAMFs). The median value of the MI increased significantly from 3 in CIN I through 4 in CIN II to 9 in CIN III (P < 0.001). The occurrence of the different LTMs was mutually correlated. The frequency of LTMs increased significantly with increasing CIN grade (P < 0.001), whereas the frequency of NMFs decreased significantly with increasing CIN grade (P < 0.001). The frequency of OAMFs was not related to CIN grade (P = 0.94). MPMs were present in low numbers in a minority of the lesions. Spearman's rank correlation coefficient (with 95% confidence limits) between the MI and the number of LTMs, OAMFs and NMFs was 0.66 (0.53; 0.75), -0.14 (-0.32; 0.05) and -0.51 (-0.63; -0.35), respectively. Increasing CIN grade is associated with increasing MI, increasing numbers of LTMs, and decreasing numbers of NMFs. MPMs are very rare events in CIN. The abundant presence of OAMFs seems to be independent of CIN grade and MI.

Summary The aim of this paper was to provide epidemiological evidence to support the notion that cervical intraepithelial neoplasia (CIN) without human papillomavirus (HPV) is a true entity. If a diagnosis of HPVnegative cervical neoplasia is erroneous, one would not expect there to be any differences in risk factors between HPV-positive and HPV-negative patients. Patients at a gynaecological outpatient clinic of a university hospital [a total of 265 consecutive women with dyskaryotic cervical smears who were subsequently diagnosed with CIN I (n = 37), CIN II (n = 48) or CIN III (n = 180)] completed a structured questionnaire regarding smoking habits and sexual history. Analysis of an endocervical swab for Chlamydia trachomatis, analysis of a cervical scrape for HPV, and morphological examination of cervical biopsy specimens were also performed. HPV was found in 205 (77.4%) out of the 265 women. Univariate analysis showed that current age (P= 0.02), current smoking behaviour (P = 0.002) and the number of sexual partners (P = 0.02) were significantly associated with the presence of HPV. Age at first sexual intercourse, a past history of venereal disease or genital warts, and current infection with Chiamydia trachomatis were not associated with the presence of HPV. Using multivariate logistic regression analysis, the number of sexual partners and current smoking behaviour showed an independent significant association with HPV. HPV-negative and HPV-positive CIN patients differ with respect to the risk factors for HPV. These findings suggest that HPV-negative CIN is a separate true entity.Keywords: cervix dysplasia; papillomavirus; risk factor Cervical intraepithelial neoplasia (CIN) is a morphologically defined lesion associated with the development of cervical carcinoma. In the conventional morphogenetic model CIN is separated into three grades according to the degree of cellular atypia and disturbance of the epithelial architecture (Richart, 1973). The infection with human papillomavirus (HPV) is strongly associated with cervical neoplasia. HPV shows considerable genetic heterogeneity (De Villiers, 1989), and a great diversity of HPV types is found in CIN Lungu et al., 1992; Bergeron et al., 1992). Known risk factors for cervical HPV infection are a comparatively young age and an increased lifetime number of sexual partners (Schiffman, 1994;Woodman, 1994). Smoking has also been identified as a risk factor 95%. Franco (1994) reported that this figure was still being scrutinised by the authors and it was likely that additional HPV-positive samples would be declared, raising the detection rate to very close to 100%. Such a result would be at odds with previous observations that HPV-negative and HPV-positive patients with squamous cell cancer of the cervix differ with respect to age and prognosis (Higgins et al., 1991;Riou et al., 1990). Opinions regarding the prevalence of HPV in CIN are fairly consistent. Schiffman (1994) mentioned that in their studies the prevalence of HPV in definite cases of CIN approached ...

* Collisions between motor vehicles and child pedestrians are a leading cause of child deaths * This study showed a strong association between increasing risk of injury of child pedestrians and increasing traffic volume * High density of curb parking was also associated with greatly increased risk of injury * Transport policies that reduce traffic volumes in urban areas could substantially reduce rates of injury ofchild pedestrians * Restricting curb parking at crossing points may also be effective at reducing risk walking for shorter journeys. Children and their parents have traditionally been held responsible for the problem of child pedestrian safety.21 Our results point to the responsibilities ofgovernment.