Targeting human papillomavirus to reduce the burden of cervical, vulvar and vaginal cancer and pre-invasive neoplasia: establishing the baseline for surveillance.

BACKGROUND: Infection with high-risk human papillomavirus (HPV) is causally related to cervical, vulvar and vaginal pre-invasive neoplasias and cancers. Highly effective vaccines against HPV types 16/18 have been available since 2006, and are currently used in many countries in combination with cervical cancer screening to control the burden of cervical cancer. We estimated the overall and age-specific incidence rate (IR) of cervical, vulvar and vaginal cancer and pre-invasive neoplasia in Denmark, Iceland, Norway and Sweden in 2004-2006, prior to the availability of HPV vaccines, in order to establish a baseline for surveillance. We also estimated the population attributable fraction to determine roughly the expected effect of HPV16/18 vaccination on the incidence of these diseases. METHODS: Information on incident cervical, vulvar and vaginal cancers and high-grade pre-invasive neoplasias was obtained from high-quality national population-based registries. A literature review was conducted to define the fraction of these lesions attributable to HPV16/18, i.e., those that could be prevented by HPV vaccination. RESULTS: Among the four countries, the age-standardised IR/105 of cervical, vaginal and vulvar cancer ranged from 8.4-13.8, 1.3-3.1 and 0.2-0.6, respectively. The risk for cervical cancer was highest in women aged 30-39, while vulvar and vaginal cancers were most common in women aged 70+. Age-standardised IR/105 of cervical, vulvar and vaginal pre-invasive neoplasia ranged between 138.8-183.2, 2.5-8.8 and 0.5-1.3, respectively. Women aged 20-29 had the highest risk for cervical pre-invasive neoplasia, while vulvar and vaginal pre-invasive neoplasia peaked in women aged 40-49 and 60-69, respectively. Over 50% of the observed 47,820 incident invasive and pre-invasive cancer cases in 2004-2006 can be attributed to HPV16/18. CONCLUSION: In the four countries, vaccination against HPV 16/18 could prevent approximately 8500 cases of gynecological cancer and pre-cancer annually. Population-based cancer and vaccination registries are essential to assess the predicted public health effects of HPV vaccination.

Cost-effectiveness of human papilloma virus vaccination in Iceland.

OBJECTIVE: To evaluate the likely cost-effectiveness of introducing routine HPV vaccination in Iceland. DESIGN: Prospective cost-effectiveness analysis of human papilloma virus (HPV) vaccination. SETTING AND SAMPLE: Population of 12-year-old girls in the Icelandic population. METHODS: A model was developed, comparing a cohort of all 12-year-old girls alive in year 2006, with or without vaccination. The model was based on the epidemiology of cervical cancer in Iceland and its premalignant stages as well as the costs involved in the treatment of each stage, assuming that the vaccines only prevent infections caused by HPV 16/18 at an efficacy of 95% and participation rate of 90%, no catch-up vaccination, no vaccination of boys and no booster dose needed. All costs were calculated on the basis of the price level of mid-year 2006 with a 3% discount rate. Incremental cost-effectiveness ratio calculations were performed and sensitivity analysis was carried out on factors most relevant for cost-effectiveness. RESULTS: Vaccination costs in excess of savings would be about euro313.000/year. Vaccination would reduce the number of women diagnosed with cervical cancer by almost 9, prevent the death of 1.7 women and result in 16.9 quality-adjusted life years gained annually. The incremental cost-effectiveness ratio was calculated to be about euro18.500/quality-adjusted life year saved. CONCLUSION: HPV vaccination seems to be cost-effective in Iceland, but this was sensitive to various parameters in the model, mainly the discount rate, the price of the vaccines and the need for a booster dose.

HPV genotypes in CIN 2-3 lesions and cervical cancer: a population-based study.

The distribution of human papillomavirus (HPV) varies between countries and continents leading to different effectiveness of upcoming prophylactic HPV vaccines. This study analyses the HPV distribution in CIN 2-3, recurrent CIN 2-3 and cervical cancer in Iceland. About 80% of incident cases with CIN 2-3 lesions in 1990 and 1999, 99% of cancer cases in 1990-1994 and 1999-2003, and cases with recurrent CIN 2-3 after conization in 1990 were tested with PCR analysis for the presence of 12 oncogenic HPV types. About 95% of the CIN 2-3 and 92% of the cancer cases tested positive for the included HPV types. HPV 16 was the most frequent type followed by HPV 33, 31, 52, 35, 18, 58, 56, 39, 45, 59 in CIN 2-3 and by HPV 18, 33 45, 31, 39, 52, 35, 51, 56 in cancer. HPV 16 and 18 were associated with a significantly increased cancer risk and HPV 52 and 31 with decreased cancer risk compared to the risk of CIN 3. The HPV distribution differed between histological cancer types, stages and age groups. The number of HPV types was not a significant predictor of cancer. Oncogenic HPV types were found in all persistent or recurrent CIN 2-3 disease after conization. Vaccination against HPV 16/18 is estimated to achieve a minimum 40% reduced rate of CIN 2-3 and a minimum 60% reduced cancer rate. This rate could, however, be increased to 95% and 92% respectively by including all the 12 HPV types tested for in this study.

Efficacy and safety of a contraceptive vaginal ring (NuvaRing) compared with a combined oral contraceptive: a 1-year randomized trial.

This open-label, randomized, Phase III study compared the efficacy and tolerability of and compliance with NuvaRing, a combined contraceptive vaginal ring releasing 15 microg of ethinylestradiol (EE) and 120 microg of etonogestrel daily, with those of and with a combined oral contraceptive (COC) containing 150 microg of levonorgestrel (LNG) and 30 microg of EE. Subjects received NuvaRing or a COC for 13 cycles (3 weeks of ring/pill treatment followed by a 1-week ring-/pill-free period). A total of 1030 subjects (NuvaRing, n=512; COC, n=518) was randomized and started treatment (intent-to-treat [ITT] population). The percentage of women in the ITT population who completed the trial was 70.9% for the NuvaRing group and 71.2% for the COC group. Five in-treatment pregnancies occurred in each group, giving Pearl indices of 1.23 for NuvaRing and 1.19 for the COC. Compliance with both treatments was excellent and both were well tolerated. In conclusion, NuvaRing has comparable efficacy and tolerability with a COC containing 150 microg of LNG and 30 microg of EE and does not require daily dosing.

Prevalence and regional differences in overweight in 2001 and trends in BMI distribution in Swedish children from 1987 to 2001.

AIMS: This study was undertaken to assess current prevalence and regional differences of overweight in 2001 and changes in body mass index (BMI) distribution between 1987 and 2001 in Swedish adolescents. METHODS: Comparison was made of two independent samples. For assessment of prevalence and regional differences in 2001, a total of 1732 subjects were used. For trend analyses a total of 1,949 children (516 and 1,470 in 1987 and 2001, respectively), aged 10, 13, and 16 years. RESULTS: The prevalence of overweight in 2001 was between 21.7% and 13.3% for boys and girls aged 10 to 16 years and the prevalence of obesity was between 2.9% and 6.2%. Mean BMI as well as prevalence of overweight and obesity was higher in subjects from schools in smaller towns or from the countryside. Median BMI among adolescents changed from 1987 to 2001, most notably in 13- and 16-year-old children. The prevalence of overweight and obesity combined has changed more than 2.5-fold in children aged 10 to 16 years. In this study, the most pronounced elevation in BMI is found in the upper part of the BMI spectrum. This change is especially apparent in girls. CONCLUSION: The change in mean BMI and prevalence of overweight and obesity in children in this study is mainly due to the pronounced change in BMI at the upper end of the spectrum, indicating that the factors leading to overweight or obesity have changed in only a subgroup of the child population.

Assessing attitude towards prioritizing in healthcare in Iceland.

The objective of the study was to access the attitude of various groups in Iceland towards some prioritizing principles and their application in healthcare. The study was a cross-sectional mailing survey including a cover letter and a prepaid envelope. It was conducted in Iceland in March through May 1995. There were two types of questionnaires, one from a hypothetical patient's perspective and the other from hypothetical planners' perspective. Both included the same demographic variables. A randomized sample of seven groups were invited to participate, i.e. physicians, politicians, and two groups from the general public, administrators and board members of health care institutions, registered nurses and licensed nurse practitioners. Only findings from the first four groups were analyzed and reported here. The response rate ranged from 46 to 75%. On average, there was strong reservation against prioritizing between different patients groups. However, physicians appear, first, to be more prepared to prioritize than other groups, and second, they had a stronger preference to opt for effective outcome rather than disease severity. Most respondents were reluctant to allocate limited resources to patients who are most seriously ill and would receive little benefit from treatment.