| 1. |
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| 2. |
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| 3. |
- Abu-Elyazeed, R R, et al.
(författare)
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Safety and immunogenicity of a glycoprotein D genital herpes vaccine in healthy girls 10-17 years of age : results from a randomised, controlled, double-blind trial
- 2013
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Ingår i: Vaccine. - : Elsevier BV. - 0264-410X .- 1873-2518. ; 31:51, s. 6136-6143
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The investigational AS04-adjuvanted herpes simplex virus type 2 (HSV-2) glycoprotein D (gD2) subunit prophylactic vaccine ('HSV vaccine'; GlaxoSmithKline Vaccines) has been shown to be well tolerated in adults, but limited data exist for pre-teen and adolescent girls, a likely target population. The primary objective of this study was to compare the occurrence of serious adverse events (SAEs) over 12 months between HSV vaccine recipients and saline recipients (placebo control group) in pre-teen and adolescent girls. The immunogenicity of the HSV vaccine was also assessed.METHODS: Healthy girls aged 10-17 years, stratified by age (10-15 years; 16-17 years), were randomised 2:1:1 to receive the HSV vaccine, a hepatitis A vaccine (Havrix™; HAV control) or placebo (saline) according to a 0-, 1-, 6-month schedule. Participants and study personnel not involved in the preparation or administration of vaccines were blinded to treatment. Safety and immunogenicity analyses were performed overall and by age (10-15 years; 16-17 years) and HSV serostatus.RESULTS: No statistically significant difference in the percentage of subjects with SAEs was observed between the HSV and saline group, or between the HSV and pooled control (HAV and saline) groups. The HSV vaccine was well tolerated, although a higher incidence of solicited local symptoms was observed in the HSV group than in the control group. Neither age nor HSV serostatus at the time of study entry had an impact on the safety profile of this vaccine. The HSV vaccine was immunogenic regardless of pre-vaccination HSV serostatus. Higher anti-gD geometric mean concentrations were observed in HSV-1 seropositive participants than in HSV-1 seronegative participants.CONCLUSION: The HSV vaccine had an acceptable safety profile, and was well tolerated and immunogenic when administered to girls aged 10-17 years regardless of age or HSV pre-vaccination serostatus.
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| 4. |
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| 5. |
- Au, A. E., et al.
(författare)
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Altered B-lymphopoiesis in mice with deregulated thrombopoietin signaling
- 2017
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- Thrombopoietin (TPO) is the master cytokine regulator of megakaryopoiesis. In addition to regulation of megakaryocyte and platelet number, TPO is important for maintaining proper hematopoietic stem cell (HSC) function. It was previously shown that a number of lymphoid genes were upregulated in HSCs from Tpo(-/-)mice. We investigated if absent or enhanced TPO signaling would influence normal B-lymphopoiesis. Absent TPO signaling in Mpl(-/-)mice led to enrichment of a common lymphoid progenitor (CLP) signature in multipotential lineage-negative Sca-1(+)c-Kit(+) (LSK) cells and an increase in CLP formation. Moreover, Mpl(-/-)mice exhibited increased numbers of PreB2 and immature B-cells in bone marrow and spleen, with an increased proportion of B-lymphoid cells in the G1 phase of the cell cycle. Conversely, elevated TPO signaling in Tpo(Tg) mice was associated with reduced B-lymphopoiesis. Although at steady state, peripheral blood lymphocyte counts were normal in both models, Mpl(-/-)E mu-myc mice showed an enhanced preneoplastic phase with increased numbers of splenic PreB2 and immature B-cells, a reduced quiescent fraction, and augmented blood lymphocyte counts. Thus, although Mpl is not expressed on lymphoid cells, TPO signaling may indirectly influence B-lymphopoiesis and the preneoplastic state in Myc-driven B-cell lymphomagenesis by lineage priming in multipotential progenitor cells.
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| 6. |
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| 8. |
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| 9. |
- Ebenhag, Sven-Christian, 1976, et al.
(författare)
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Two-way coherent frequency transfer in a commercial DWDM communication network in Sweden
- 2015
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Ingår i: 2015 Joint Conference of the IEEE International Frequency Control Symposium and the European Frequency and Time Forum, FCS 2015 - Proceedings. - 1075-6787. - 9781479988662 ; , s. 276-279
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Konferensbidrag (refereegranskat)abstract
- An experimental fiber link is being established between SP Technical Research Institute of Sweden in Boras and Chalmers University of Gothenburg in Sweden. The one way fiber length is about 60 km and implemented in SUNET (Swedish University Network). The aim of the project is to evaluate the signal quality when sending a stable optical frequency utilizing a wavelength in a DWDM (Dense Wavelength Division Multiplexing) system fiber pair. The experiment uses a channel in the DWDM with the wavelength of 1542.14 nm. This wavelength is within the C band and is therefore compatible with common Erbium doped amplifiers in this network. Another aim of the system is to be ultra-stable which corresponds to a stability of 1×10-13 for τ = 1 s as well as providing the ability to distribute monitored ultra-stable frequency with a future traceability to UTC (SP) (National realization of Universal Time Coordinated within Sweden) to multiple users within the network. Measurements of an optical frequency transfer using a fiber-link based on unidirectional light signals in parallel fibers have shown promising results in a free-running setup and in a lab environment. The fractional frequency stability, analyzed as the Overlapping Allan deviation, is approximately 3×10-13 at τ = 10 s and almost 1×10-14 at 105 s.
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| 10. |
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| 11. |
- Hiensch, Martin, et al.
(författare)
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Two-material rail development : field test results regarding rolling contact fatigue and squeal behaviour
- 2005
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Ingår i: Wear. - : Elsevier BV. - 0043-1648 .- 1873-2577. ; 258:7-8, s. 964-972
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Tidskriftsartikel (refereegranskat)abstract
- Results from the European 5th Framework project “InfraStar” are presented. The InfraStar project is developing a two-material rail to increase the productivity and reliability of rail infrastructure. The two-material rail aims to be rolling contact fatigue (RCF) resistant and to reduce squeal noise.The InfraStar consortium has built a high level of wheel–rail expertise and understanding regarding RCF initiation and development, level and position of wheel–rail contact forces, and new interface materials and has gained experience in both laboratory and field test operating conditions. Within the project a validated theoretical train–track interaction model and a fatigue design model for two-material rails have been developed.This paper focuses on the field test results of the two-material rail, and how the predictions and expectations from the selection process match with the results observed in track. Results are very promising. The two-material rail prototypes, now over 1 year in track, show no RCF damage where the non-treated rail shows clear RCF damage. The development of the application process and other objectives of the InfraStar project are discussed.
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| 12. |
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| 13. |
- Jakobsen, Lasse H., et al.
(författare)
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Minimal relapse risk and early normalization of survival for patients with Burkitt lymphoma treated with intensive immunochemotherapy : an international study of 264 real-world patients
- 2020
-
Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 189:4, s. 661-671
-
Tidskriftsartikel (refereegranskat)abstract
- Non-endemic Burkitt lymphoma (BL) is a rare germinal centre B-cell-derived malignancy with the genetic hallmark of MYC gene translocation and with rapid tumour growth as a distinct clinical feature. To investigate treatment outcomes, loss of lifetime and relapse risk in adult BL patients treated with intensive immunochemotherapy, retrospective clinic-based and population-based lymphoma registries from six countries were used to identify 264 real-world patients. The median age was 47 years and the majority had advanced-stage disease and elevated LDH. Treatment protocols were R-CODOX-M/IVAC (47%), R-hyper-CVAD (16%), DA-EPOCH-R (11%), R-BFM/GMALL (25%) and other (2%) leading to an overall response rate of 89%. The two-year overall survival and event-free survival were 84% and 80% respectively. For patients in complete remission/unconfirmed, the two-year relapse risk was 6% but diminished to 0·6% for patients reaching 12 months of post-remission event-free survival (pEFS12). The loss of lifetime for pEFS12 patients was 0·4 (95% CI: −0·7 to 2) months. In conclusion, real-world outcomes of adult BL are excellent following intensive immunochemotherapy. For pEFS12 patients, the relapse risk was low and life expectancy similar to that of a general population, which is important information for developing meaningful follow-up strategies with increased focus on survivorship and less focus on routine disease surveillance.
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| 14. |
- Josefsson, Agnetha M., et al.
(författare)
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p53 polymorphism and risk of cervical cancer
- 1998
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 396:6711, s. 531-
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Tidskriftsartikel (refereegranskat)
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| 15. |
- Josefsson, Agnetha M., et al.
(författare)
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Viral load of human papilloma virus 16 as a determinant for development of cervical carcinoma in situ : a nested case-control study
- 2000
-
Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 355:9222, s. 2189-2193
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Infection with certain types of human papillomavirus (HPV), which is common among young women, increases the risk of cervical cancer. However, less than 1% of young women positive for oncogenic types of HPV develop cervical cancer. We investigated whether the amount of HPV DNA is a useful predictor of progression to cervical carcinoma in situ. METHODS: We estimated the amount of HPV 16 DNA by a PCR that uses the 5'-exonuclease (Taqman) method, in 478 women with cervical carcinoma in situ and 608 individually matched controls. To adjust for differences in the amount of genomic DNA between samples, we estimated the amount of a nuclear gene (beta-actin). We studied multiple smears (total 3835 archived samples) from each woman, taken over periods of up to 26 years, that covered normal cytology to development of cervical cancer. FINDINGS: The risk of cervical carcinoma in situ increased with the amount of HPV 16 DNA. Analysis of the first smear from each woman, collected a mean of 7.8 years before cancer diagnosis, showed that women with the 20% highest amount of HPV 16 DNA were at a 60-fold higher risk of developing cervical carcinoma in situ than women negative for HPV 16. The first smear samples were classified as normal by squamous-cell cytology. INTERPRETATION: Analysis of the amount of HPV DNA can predict cancer risk at a stage when current screening methods are uninformative. Testing for the amount of HPV 16 DNA during gynaecological health checks might strikingly improve our ability to distinguish between infections that have a high or low risk of progressing into cervical cancer.
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| 16. |
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| 17. |
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| 18. |
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| 19. |
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| 20. |
- Josefsson, Per O, et al.
(författare)
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Jones fracture. Surgical versus nonsurgical treatment
- 1994
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Ingår i: Clinical Orthopaedics and Related Research. - 0009-921X. ; 299, s. 252-255
-
Tidskriftsartikel (refereegranskat)abstract
- Sixty-three patients with 66 transverse and short oblique fractures of the proximal shaft of the fifth metatarsal bone (Jones fracture) were evaluated an average of five years (range, one to ten years) after the injury. There were 27 acute fractures and 39 chronic, or stress, fractures. The primary treatment was surgical for one third of the injuries and nonsurgical for the others. Surgical treatment consisted of the insertion of medullary screws. Nonsurgical treatment consisted of the application of either a plaster cast or an elastic bandage. Almost one fourth of the fractures treated nonsurgically later had to be treated surgically because of delayed unions or refractures. Late surgery was required in 12% of acute fractures and in 50% of chronic fractures with sclerosis narrowing the medullary canal. Irrespective of the primary treatment, all the patients had full function at the time of the follow-up evaluation, and no nonunions were diagnosed.
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| 21. |
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| 22. |
- Kunnus, K., et al.
(författare)
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Identification of the dominant photochemical pathways and mechanistic insights to the ultrafast ligand exchange of Fe(CO)(5) to Fe(CO)(4)EtOH
- 2016
-
Ingår i: Structural Dynamics. - : AIP Publishing. - 2329-7778. ; 3:4
-
Tidskriftsartikel (refereegranskat)abstract
- We utilized femtosecond time-resolved resonant inelastic X-ray scattering and ab initio theory to study the transient electronic structure and the photoinduced molecular dynamics of a model metal carbonyl photocatalyst Fe(CO)(5) in ethanol solution. We propose mechanistic explanation for the parallel ultrafast intra-molecular spin crossover and ligation of the Fe(CO)(4) which are observed following a charge transfer photoexcitation of Fe(CO)(5) as reported in our previous study [ Wernet et al., Nature 520, 78 (2015)]. We find that branching of the reaction pathway likely happens in the (1)A(1) state of Fe(CO)(4). A sub-picosecond time constant of the spin crossover from B-1(2) to B-3(2) is rationalized by the proposed B-1(2) -> (1)A(1) -> B-3(2) mechanism. Ultrafast ligation of the B-1(2) Fe(CO)(4) state is significantly faster than the spin-forbidden and diffusion limited ligation process occurring from the B-3(2) Fe(CO)(4) ground state that has been observed in the previous studies. We propose that the ultrafast ligation occurs via B-1(2) -> (1)A(1) -> (1)A'Fe(CO)(4)EtOH pathway and the time scale of the (1)A(1) Fe(CO)(4) state ligation is governed by the solute-solvent collision frequency. Our study emphasizes the importance of understanding the interaction of molecular excited states with the surrounding environment to explain the relaxation pathways of photoexcited metal carbonyls in solution.
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| 23. |
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| 24. |
- Lindgren, Lars-Erik, et al.
(författare)
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Thermo-mechanical FE-analysis of residual stresses and stress redistribution in butt welding of a copper canister for spent nuclear fuel
- 2002
-
Ingår i: Nuclear Engineering and Design. - 0029-5493 .- 1872-759X. ; 212:1-3, s. 401-408
-
Tidskriftsartikel (refereegranskat)abstract
- The transient and residual temperature, stress and strain field present during electron beam welding of a plane copper end to a canister for spent nuclear fuel is calculated by the use of FEM. The subsequent stress redistribution is calculated up to 10,000 years. The canister consists of two concentric cylinders, an inner steel cylinder containing the spent nuclear fuel and an outer copper cylinder. It was found that the maximum plastic strain (plastic+creep) accumulated in the (possibly brittle) heat affected zone is ≈7%, which seems to be well below the reported ductility for the copper used.
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| 25. |
- Majidi, Danial, et al.
(författare)
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Quantum Confinement Suppressing Electronic Heat Flow below the Wiedemann–Franz Law
- 2022
-
Ingår i: Nano Letters. - : American Chemical Society (ACS). - 1530-6984 .- 1530-6992. ; 22:2, s. 630-635
-
Tidskriftsartikel (refereegranskat)abstract
- The Wiedemann–Franz law states that the charge conductance and the electronic contribution to the heat conductance are proportional. This sets stringent constraints on efficiency bounds for thermoelectric applications, which seek a large charge conduction in response to a small heat flow. We present experiments based on a quantum dot formed inside a semiconducting InAs nanowire transistor, in which the heat conduction can be tuned significantly below the Wiedemann–Franz prediction. Comparison with scattering theory shows that this is caused by quantum confinement and the resulting energy-selective transport properties of the quantum dot. Our results open up perspectives for tailoring independently the heat and electrical conduction properties in semiconductor nanostructures.
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| 26. |
- Meyer, L, et al.
(författare)
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Validation of an empiric method for safety assessment of multi remote tower
- 2019
-
Ingår i: 13th USA/Europe Air Traffic Management Research and Development Seminar 2019. - : EUROCONTROL. - 9781510893504
-
Konferensbidrag (refereegranskat)abstract
- The novel multi remote tower concept involves the control of two airports by one tower controller from one remote workplace at a time. In order to implement a multi remote tower into operations, a safety assessment is crucial to evaluate existing risks. Since there is currently no operational experience available concerning this concept, the hazard identification and risk mitigation remains hypothetical. However, empiric data is needed for evaluating and focusing on the safety-relevant hazards that are multi remote tower specific. To close this gap, we developed the MERASSA concept for gaining evidence on the safety-relevance of hazard using Human-In-The-Loop simulations and stress test scenarios. The method was assessed through a validation study at the multi remote tower case using eight identified hazards that are human-issue originated. In total 32 simulation runs with eight rated and experienced tower controllers were carried out. The results of the study show the ability of the tower controller to compensate risk by slowing down the work speed. No hazard could be verified through a comparison of the multi and single runway baseline scenario. Additionally, the results indicate a clear lack of confidence of the tower controller to control two airports at a time due to the need to share attention across the work environment. The comparison of the empiric and subjective results show equal trends which are a sign for the success of applying the method. However, a major drawback of using simulations and stress test scenarios are the enormous efforts needed to control the conditions of testing
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| 27. |
- Moro, F., et al.
(författare)
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Imaging in gynecological disease (20) : clinical and ultrasound characteristics of adnexal torsion
- 2020
-
Ingår i: Ultrasound in Obstetrics and Gynecology. - : Wiley. - 0960-7692 .- 1469-0705. ; 56:6, s. 934-943
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives: To describe the clinical and ultrasound characteristics of adnexal torsion. Methods: This was a retrospective study. From the operative records of the eight participating gynecological ultrasound centers, we identified patients with a surgically confirmed diagnosis of adnexal torsion, defined as surgical evidence of ovarian pedicle, paraovarian cyst and/or Fallopian tube twisted on its own axis, who had undergone preoperative ultrasound examination by an experienced examiner, between 2008 and 2018. Only cases with at least two available ultrasound images and/or videoclips (one grayscale and one with Doppler evaluation) were included. Clinical, ultrasound, surgical and histological information was retrieved from each patient's medical record and entered into an Excel file by the principal investigator at each center. In addition, two authors reviewed all available ultrasound images and videoclips of the twisted adnexa, with regard to the presence of four predefined ultrasound features reported to be characteristic of adnexal torsion: (1) ovarian stromal edema with or without peripherally displaced antral follicles, (2) the follicular ring sign, (3) the whirlpool sign and (4) absence of vascularization in the twisted organ. Results: A total of 315 cases of adnexal torsion were identified. The median age of the patients was 30 (range, 1–88) years. Most patients were premenopausal (284/314; 90.4%) and presented with acute or subacute pelvic pain (305/315; 96.8%). The surgical approach was laparoscopic in 239/312 (76.6%) patients and conservative surgery (untwisting with or without excision of a lesion) was performed in 149/315 (47.3%) cases. According to the original ultrasound reports, the median largest diameter of the twisted organ was 83 (range, 30–349) mm. Free fluid in the pouch of Douglas was detected in 196/275 (71.3%) patients. Ovarian stromal edema with or without peripherally displaced antral follicles was reported in the original ultrasound report in 167/241 (69.3%) patients, the whirlpool sign in 178/226 (78.8%) patients, absent color Doppler signals in the twisted organ in 119/269 (44.2%) patients and the follicular ring sign in 51/134 (38.1%) patients. On retrospective review of images and videoclips, ovarian stromal edema with or without peripherally displaced antral follicles (201/254; 79.1%) and the whirlpool sign (139/153; 90.8%) were the most commonly detected features of adnexal torsion. Conclusion: Most patients with surgically confirmed adnexal torsion are of reproductive age and present with acute or subacute pain. Common ultrasound signs are an enlarged adnexa, the whirlpool sign, ovarian stromal edema with or without peripherally displaced antral follicles and free fluid in the pelvis. The follicular ring sign and absence of Doppler signals in the twisted organ are slightly less common signs. Recognizing ultrasound signs of adnexal torsion is important so that the correct treatment, i.e. surgery without delay, can be offered.
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| 28. |
- Petersen, Jens Kjerulf, et al.
(författare)
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Reference conditions and EQOs for aquatic vegetation and macrozoobenthos.
- 2005
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Ingår i: Final report from The project RETRO - ”Reference conditions and typologies for aquatic vegetation and macrozoobenthos in the Skagerrak and Kattegat” - is an 2002-4 RTD-project funded by Nordic Council of Ministers involving partners from Denmark, Norway and Sweden..
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 29. |
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| 30. |
- Sahlin, Nils-Eric, et al.
(författare)
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Ethical aspects of valuing lives
- 1994
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Ingår i: Future Risks and Risk Management. - 0792330579 ; , s. 93-124
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 31. |
- Sommer, Felix, et al.
(författare)
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The Gut Microbiota Modulates Energy Metabolism in the Hibernating Brown Bear Ursus arctos
- 2016
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Ingår i: Cell Reports. - Cambridge, USA : Elsevier BV. - 2211-1247. ; 14:7, s. 1655-1661
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Tidskriftsartikel (refereegranskat)abstract
- Hibernation is an adaptation that helps many animals to conserve energy during food shortage in winter. Brown bears double their fat depots during summer and use these stored lipids during hibernation. Although bears seasonally become obese, they remain metabolically healthy. We analyzed the microbiota of free-ranging brown bears during their active phase and hibernation. Compared to the active phase, hibernation microbiota had reduced diversity, reduced levels of Firmicutes and Actinobacteria, and increased levels of Bacteroidetes. Several metabolites involved in lipid metabolism, including triglycerides, cholesterol, and bile acids, were also affected by hibernation. Transplantation of the bear microbiota from summer and winter to germ-free mice transferred some of the seasonal metabolic features and demonstrated that the summer microbiota promoted adiposity without impairing glucose tolerance, suggesting that seasonal variation in the microbiota may contribute to host energy metabolism in the hibernating brown bear.
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| 32. |
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| 33. |
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| 34. |
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| 35. |
- Vult von Steyern, Fredrik, et al.
(författare)
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Lysosomotropic agents activate the capacity for calcium dependent pinocytosis in starved Amoeba proteus: Evidence for a mechanism involving phospholipase A2.
- 1996
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Ingår i: Protoplasma. - 1615-6102. ; 192:1-2, s. 20-27
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Tidskriftsartikel (refereegranskat)abstract
- Pinocytosis induced by Na+ was assayed by phase contrast microscopy in 8–12 days starvedAmoeba proteus. These cultures were inactive with respect to calcium-dependent Na+-induced pinocytosis, but treatment with amino acid methyl and ethyl esters increased their capacity for pinocytosis. Besides promoting pinocytosis these compounds also stimulated calcium-sensitive secretion of lysosomal enzymes from normal, 2–3 days starved, cells. Only uncharged 1-forms of the amino acid esters were effective. Also other lysosomotropic compounds including monodansylcadaverine, glycine-phenylalanine-2-naphthylamide, NH4Cl, and the ionophores monensin and A23187 activated starved cells. The effect of these agents (except A23187) was inhibited by the drug dantrolene suggesting that activation is a consequence of release of Ca2+ from intracellular stores. Several of the lysosomotropic agents also lost their activating effect in the presence of phospholipase A2 (PLA2) inhibitors. To investigate whether or not PLA2 activity in the cell culture could imitate the effect of the lysosomotropic agents, we incubated starved cells with snake venom PLA2s. These enzymes caused rapid, dantrolene-sensitive activation of the cells. Measurement of endogenous PLA2in ldquonormalrdquo cells revealed significant cellular activity but no significant secretion of the enzyme into the culture medium was observed. Together the studies with enzyme inhibitors and dantrolene suggest that the process by which lysosomotropic agents affect pinocytosis involves activation of PLA2 and release of Ca2+ from intracellular stores.
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| 36. |
- Wikell, Cecilia, et al.
(författare)
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Disposition of venlafaxine enantiomers in rats with hepatic encephalopathy after chronic drug treatment.
- 2002
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Ingår i: Chirality. - : Wiley. - 1520-636X .- 0899-0042. ; 14:4, s. 347-350
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Tidskriftsartikel (refereegranskat)abstract
- Portacaval shunted (PCS) rats, a model of hepatic encephalopathy, and control animals were administered racemic venlafaxine for 14 days (10 mg/kg). The levels of the S- and R-enantiomers and the S/R-enantiomer ratios of venlafaxine and its metabolites were assessed by an enantiomer-selective chromatographic assay in serum, brain parenchyma, and brain dialysate of both groups. Higher levels of the S- and R-enantiomers of venlafaxine were found in serum and brain of PCS vs. normal rats (median values of S- and R-venlafaxine in serum: 290 and 201 nM in PCS; 97 and 66 nM in normal rats; median values of S- and R-venlafaxine in cortex: 956 and 939 nM in PCS; 357 and 318 nM in normal rats). Interestingly, similar S/R-venlafaxine ratios were observed in PCS and normal rats both in serum (S/R = 1.4) and brain compartments (S/R = l.0-1.1). These findings may have clinical relevance for the safety of venlafaxine in chronic hepatic encephalopathy.
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| 37. |
- Ylitalo, Nathalie, et al.
(författare)
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Consistent high viral load of human papillomavirus 16 and risk of cervical carcinoma in situ : a nested case-control study
- 2000
-
Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 355:9222, s. 2194-2198
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Persistent infection with certain types of human papillomavirus (HPV) is believed to be a prerequisite for the development of cervical neoplasia. Persistence may depend on certain characteristics, such as viral load, which has so far been given little attention. We investigated the association between HPV 16 viral load and cervical carcinoma in situ. METHODS: We did a nested case-control study of women participating in cytological screening in Sweden. We used a sensitive quantitative PCR assay to estimate HPV 16 load in multiple smears for each woman, taken during a period of up to 26 years before diagnosis. We calculated C, values, which decrease as the number of viral DNA copies increases. FINDINGS: 2081 smears from 478 cases and 1754 smears from 608 controls were tested. Among cases, we found a consistently increased load of HPV 16 already 13 years or more before diagnosis, and when many smears were still cytologically normal. Women with high HPV 16 viral loads were at least 30 times the relative risk of HPV-16-negative women more than a decade before diagnosis. The increase in relative risk was constant over time. About 25% of women (95% CI 0.12-0.32) infected with a high viral load before age 25 years developed cervical carcinoma in situ within 15 years. INTERPRETATION: Cervical carcinoma in situ associated with HPV 16 occurs mainly in HPV-16-positive women who have consistently high viral loads long term. Women at high risk could be identified by use of a quantitative HPV test in addition to cytological screening.
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