A randomized controlled trial of Human Papillomavirus (HPV) testing for cervical cancer screening: trial design and preliminary results (HPV FOCAL Trial).

BACKGROUND: In the HPV FOCAL trial, we will establish the efficacy of hr-HPV DNA testing as a stand-alone screening test followed by liquid based cytology (LBC) triage of hr-HPV-positive women compared to LBC followed by hr-HPV triage with > or = CIN3 as the outcome. METHODS/DESIGN: HPV-FOCAL is a randomized, controlled, three-armed study over a four year period conducted in British Columbia. It will recruit 33,000 women aged 25-65 through the province's population based cervical cancer screening program. Control arm: LBC at entry and two years, and combined LBC and hr-HPV at four years among those with initial negative results and hr-HPV triage of ASCUS cases; Two Year Safety Check arm: hr-HPV at entry and LBC at two years in those with initial negative results with LBC triage of hr-HPV positives; Four Year Intervention Arm: hr-HPV at entry and combined hr-HPV and LBC at four years among those with initial negative results with LBC triage of hr-HPV positive cases DISCUSSION: To date, 6150 participants have a completed sample and epidemiologic questionnaire. Of the 2019 women enrolled in the control arm, 1908 (94.5%) were cytology negative. Women aged 25-29 had the highest rates of HSIL (1.4%). In the safety arm 92.2% of women were hr-HPV negative, with the highest rate of hr-HPV positivity found in 25-29 year old women (23.5%). Similar results were obtained in the intervention arm HPV FOCAL is the first randomized trial in North America to examine hr-HPV testing as the primary screen for cervical cancer within a population-based cervical cancer screening program. TRIAL REGISTRATION: International Standard Randomised Controlled Trial Number Register, ISRCTN79347302.

Parental intention to have daughters receive the human papillomavirus vaccine.

BACKGROUND: Concerns have been raised that parents may be reluctant to have their daughters receive the human papillomavirus (HPV) vaccine, because of a belief that doing so might be interpreted as condoning earlier and more frequent sexual activity. We determined intentions regarding vaccination among Canadian parents and factors that predicted parental intention to have their daughters vaccinated against HPV. METHODS: Parents of children 8-18 years of age, recruited from across Canada, were asked to respond to questions in the context of a grade 6, publicly funded, school-based HPV vaccine program. We performed backward logistic regression analysis to identify factors predictive of parents' intention to have their daughters vaccinated against HPV. RESULTS: Of the 1350 respondents with female children, more than 70% (73.8%; 95% confidence interval [CI] 71.5%-76.1%) intended to have their daughters undergo vaccination against HPV. In multivariable modelling, parents who had positive attitudes toward vaccines (odds ratio [OR] 9.9, 95% CI 4.7-21.1), those who were influenced by subjective norms (OR 9.2, 95% CI 6.6-12.9), those who felt that the vaccine had limited influence on sexual behaviour (OR 3.2, 95% CI 2.2-4.6) and those who thought someone they knew was likely to get cervical cancer (OR 1.5, 95% CI 1.1-2.1) were more likely to intend that their daughters receive the HPV vaccine. Parents who were older (v. younger) (OR 0.6, 95% CI 0.4-0.8) and those who resided in British Columbia or Yukon Territory (v. Atlantic Canada) (OR 0.5, 95% CI 0.3-0.9) were less likely to intend that their daughters receive the HPV vaccine. INTERPRETATION: Most of the parents surveyed intended that their daughters would receive vaccination against HPV. Overall attitudes toward vaccines in general and toward the HPV vaccine in particular constituted the most significant predictor of parental intention with regard to vaccination.

Proteomic analysis of a preneoplastic phenotype in ovarian surface epithelial cells derived from prophylactic oophorectomies.

OBJECTIVE: To study the pattern of protein expression associated with a predisposition to develop ovarian cancer. METHODS: Prophylactic oophorectomy is used to prevent ovarian carcinoma in high-risk populations who have a strong family history of breast/ovarian cancer. In ovarian specimens of these women, the ovarian surface epithelium (OSE), which is tissue of origin of epithelial ovarian cancer, often shows altered morphology, growth patterns and differentiation features that are believed to be preneoplastic. This study has used a proteomic approach, based on two-dimensional gel electrophoresis and mass spectrometry, to compare the protein profiles of OSE from women with a history of familial ovarian cancer (FH-OSE), i.e., at least two first-degree relatives with such cancer and/or testing positive for BRCA1 mutations, to those without such history (NFH-OSE). RESULTS: Of >1500 protein spots, there were 8 proteins whose levels were significantly altered in FH-OSE. Three were known ovarian tumor associated proteins, others were novel changes. A number of the alterations seen were accompanied with protein modifications and have not been previously reported. There was a predominance of sequences related to the stress response pathway. Differential expression of selected genes was confirmed by Western blotting and real-time reverse transcription polymerase chain reaction. CONCLUSIONS: Our findings define the OSE phenotype of women at a high risk of developing ovarian cancer. Protein alterations seen in these tissues may represent an early, irreversible, non-mutational step in ovarian epithelial neoplastic progression and may be potential early and sensitive markers for the evaluation of cancer risk.

Advanced-stage serous borderline tumors of the ovary: a clinicopathological study of 49 cases.

There is controversy about patient outcomes and pathological parameters of prognostic significance in patients with stage II or stage III ovarian serous borderline tumors. Forty-nine cases of stage II and III ovarian serous borderline tumors were identified on review of the medical records at Vancouver Hospital and British Columbia Cancer Agency for the period from 1979 to 1996. Pathological features assessed included presence of micropapillary architecture, tumor cell DNA content (ploidy), and characteristics of the extraovarian implants, including invasiveness and mitotic activity. Clinical follow-up information (3-17 years of follow-up) was obtained for 48 patients. Fifteen patients had stage II tumors and 34 had stage III tumors. Fourteen patients experienced tumor recurrence 1 to 8 (mean 3.5) years after presentation and of these, six patients died of disease (2, 3, 4, 7, 10, and 11 years after presentation). Patients with gross residual disease, as assessed by the surgeon, more frequently experienced a recurrence compared with patients without gross residual disease, but this difference did not reach statistical significance (0.05