A total of 308,036 women were selected from the European Prospective Investigation into Cancer and Nutrition (EPIC) study to evaluate the association between tobacco smoking and the risk of cervical intraepithelial neoplasia of grade 3 (CIN3)/carcinoma in situ (CIS) and invasive cervical cancer (ICC). At baseline, participants completed a questionnaire and provided blood samples. During a mean follow‐up time of 9 years, 261 ICC cases and 804 CIN3/CIS cases were reported. In a nested case–control study, the baseline sera from 609 cases and 1,218 matched controls were tested for L1 antibodies against HPV types 11, 16, 18, 31, 33, 35, 45, 52, 58, and antibodies against Chlamydia trachomatis (CT), and Human Herpes Virus 2 (HHV‐2). Cervical samples were not available for HPV‐DNA analysis in this study. Multivariate analyses were used to estimate associations between smoking and risk of CIN3/CIS and ICC in the cohort and the case–control studies. In the cohort analyses smoking status, duration and intensity showed a two‐fold increased risk of CIN3/CIS and ICC, while time since quitting was associated with a two‐fold reduced risk. In the nested case–control study, consistent associations were observed after adjustment for HPV, CT and HHV‐2 serostatus, in both HPV seronegative and seropositive women. Results from this large prospective study confirm the role of tobacco smoking as an important risk factor for both CIN3/CIS and ICC, even after taking into account HPV exposure as determined by HPV serology. The strong beneficial effect of quitting smoking is an important finding that will further support public health policies for smoking cessation.

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Background: The quadrivalent human papillomavirus (qHPV) vaccine prevented vaccine HPV type-related infection and disease in young women in the 4-year FUTURE II efficacy study (NCT00092534). We report long-term effectiveness and immunogenicity at the end of 14 years of follow-up after enrollment in FUTURE II. Methods: Young women (16À23 years of age) from Denmark, Iceland, Norway, and Sweden who received three qHPV vaccine doses during the randomized, double-blind, placebo-controlled FUTURE II base study were followed for effectiveness for an additional 10 years through national registries. Tissue samples including but not limited to those collected during organized cervical cancer screening programs were obtained from regional biobanks to be adjudicated for histopathology diagnosis and tested for HPV DNA. The observed incidence of HPV16/18-related high-grade cervical dysplasia (primary outcome) was compared with recent historical background incidence rates in an unvaccinated population. Serum was collected at years 9 and 14 to assess antibody responses. Findings: No cases of HPV16/18-related high-grade cervical dysplasia were observed in the per-protocol effectiveness population (N = 2121; 24,099¢0 person-years of follow-up) during the entire study. Vaccine effectiveness of 100% (95% CI 94¢7À100) was demonstrated for 12 years, with a trend toward continued protection through 14 years post-vaccination. Seropositivity rates at study conclusion were >90% (HPV6/11/16) and 52% (HPV18) using competitive Luminex immunoassay, and >90% (all four HPV types) using the more sensitive IgG Luminex immunoassay. Interpretation: Vaccination of young women with qHPV vaccine offers durable protection against HPV16/18-related high-grade cervical dysplasia for 12 years, with a trend toward continued protection through 14 years post-vaccination, and induces sustained HPV6/11/16/18 antibody responses for up to 14 years post-vaccination. There was no evidence of waning immunity, suggesting no need for a booster dose during that period.

Immunosuppression involves an inability to control virus infections and increased incidence of virus-associated cancers. Some cancers without known viral etiology are also increased, but data on exactly which cancer forms are increased has been inconsistent. To provide a reliable and generalizable estimate, with high statistical power and long follow-up time, we assessed cancer risks using comprehensive, population-based registries in two different countries and from two different immunosuppressed patient groups (solid organ transplant recipients (OTRs) and long-term dialysis patients (LDPs)). National registries in Denmark and Sweden identified 20,804 OTRs and 31,140 LDPs that were followed up using national cancer registries. Standardized incidence ratios (SIR) compared to the general population were estimated. We found highly similar results, both for the two different countries and for the two different immunosuppressed cohorts, namely an increased incidence for the following specific cancer forms: Non-melanoma skin cancer (NMSC), non-Hodgkin's lymphoma and cancers of the lip, kidney, larynx and thyroid. The SIR for overall cancer among OTRs was 3.5 [n = 2,142, 95% CI, 3.4-3.7] in Sweden, 2.9 [n = 1,110, 95% CI, 2.8-3.1] in Denmark and 1.6 [n = 1,713, 95% CI, 1.5-1.6] among LDP. The SIR for NMSC among OTRs was 44.7 [n = 994, 95% CI, 42-47.5] in Sweden and 41.5 [n = 445, 95% CI, 37.8-45.5] in Denmark. The increased SIR for NMSC among LDPs was 5.3 [n = 304, 95% CI, 4.7-5.9]). In summary, an increased SIR for a specific, similar set of cancer forms is consistently found among the immunosuppressed. Conceivable explanations include surveillance bias and immunosuppression-related susceptibility to viral infections.

V501-015.