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Bradbury, K. E., Appleby, P. N., Tipper, S. J., Travis, R. C., Allen, N. E., Kvaskoff, M., . . . Key, T. J. (2019). Circulating insulin-like growth factor I in relation to melanoma risk in the European prospective investigation into cancer and nutrition. International Journal of Cancer, 144(5), 957-966
Open this publication in new window or tab >>Circulating insulin-like growth factor I in relation to melanoma risk in the European prospective investigation into cancer and nutrition
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2019 (English)In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 144, no 5, p. 957-966Article in journal (Refereed) Published
Abstract [en]

Insulin-like growth factor-I (IGF-I) regulates cell proliferation and apoptosis, and is thought to play a role in tumour development. Previous prospective studies have shown that higher circulating concentrations of IGF-I are associated with a higher risk of cancers at specific sites, including breast and prostate. No prospective study has examined the association between circulating IGF-I concentrations and melanoma risk. A nested case-control study of 1,221 melanoma cases and 1,221 controls was performed in the European Prospective Investigation into Cancer and Nutrition cohort, a prospective cohort of 520,000 participants recruited from 10 European countries. Conditional logistic regression was used to estimate odds ratios (ORs) for incident melanoma in relation to circulating IGF-I concentrations, measured by immunoassay. Analyses were conditioned on the matching factors and further adjusted for age at blood collection, education, height, BMI, smoking status, alcohol intake, marital status, physical activity and in women only, use of menopausal hormone therapy. There was no significant association between circulating IGF-I concentration and melanoma risk (OR for highest vs lowest fifth = 0.93 [95% confidence interval [CI]: 0.71 to 1.22]). There was no significant heterogeneity in the association between IGF-I concentrations and melanoma risk when subdivided by gender, age at blood collection, BMI, height, age at diagnosis, time between blood collection and diagnosis, or by anatomical site or histological subtype of the tumour (Pheterogeneity≥0.078). We found no evidence for an association between circulating concentrations of IGF-I measured in adulthood and the risk of melanoma.

Place, publisher, year, edition, pages
John Wiley & Sons, 2019
Keywords
EPIC, biomarker, height, insulin-like growth factor I, melanoma, prospective studies
National Category
Surgery
Identifiers
urn:nbn:se:umu:diva-154639 (URN)10.1002/ijc.31854 (DOI)000455041700004 ()30191956 (PubMedID)
Funder
Swedish Cancer SocietySwedish Research Council
Available from: 2018-12-21 Created: 2018-12-21 Last updated: 2019-02-11Bibliographically approved
Rutegård, M., Båtsman, M., Axelsson, J., Brynolfsson, P., Brännström, F., Rutegård, J., . . . Riklund, K. (2019). PET/MRI and PET/CT hybrid imaging of rectal cancer - description and initial observations from the RECTOPET (REctal Cancer trial on PET/MRI/CT) study. Cancer Imaging, 19, Article ID 52.
Open this publication in new window or tab >>PET/MRI and PET/CT hybrid imaging of rectal cancer - description and initial observations from the RECTOPET (REctal Cancer trial on PET/MRI/CT) study
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2019 (English)In: Cancer Imaging, ISSN 1740-5025, E-ISSN 1470-7330, Vol. 19, article id 52Article in journal (Refereed) Published
Abstract [en]

PurposeThe role of hybrid imaging using F-18-fluoro-2-deoxy-D-glucose positron-emission tomography (FDG-PET), computed tomography (CT) and magnetic resonance imaging (MRI) to improve preoperative evaluation of rectal cancer is largely unknown. To investigate this, the RECTOPET (REctal Cancer Trial on PET/MRI/CT) study has been launched with the aim to assess staging and restaging of primary rectal cancer. This report presents the study workflow and the initial experiences of the impact of PET/CT on staging and management of the first patients included in the RECTOPET study.MethodsThis prospective cohort study, initiated in September 2016, is actively recruiting patients from Region Vasterbotten in Sweden. This pilot study includes patients recruited and followed up until December 2017. All patients had a biopsy-verified rectal adenocarcinoma and underwent a minimum of one preoperative FDG-PET/CT and FDG-PET/MRI examination. These patients were referred to the colorectal cancer multidisciplinary team meeting at Umea University Hospital. All available data were evaluated when making management recommendations. The clinical course was noted and changes consequent to PET imaging were described; surgical specimens underwent dedicated MRI for anatomical matching between imaging and histopathology.ResultsTwenty-four patients have so far been included in the study. Four patients were deemed unresectable, while 19 patients underwent or were scheduled for surgery; one patient was enrolled in a watch-and-wait programme after restaging. Consequent to taking part in the study, two patients were upstaged to M1 disease: one patient was diagnosed with a solitary hepatic metastasis detected using PET/CT and underwent metastasectomy prior to rectal cancer surgery, while one patient with a small, but metabolically active, lung nodulus experienced no change of management. PET/MRI did not contribute to any recorded change in patient management.ConclusionsThe RECTOPET study investigating the role of PET/CT and PET/MRI for preoperative staging of primary rectal cancer patients will provide novel data that clarify the value of adding hybrid to conventional imaging, and the role of PET/CT versus PET/MRI.Trial registrationNCT03846882.

Place, publisher, year, edition, pages
BMC, 2019
Keywords
Rectal neoplasm, Rectal tumour, Staging, Lymph nodes, Tumour deposits, PET, CT, FDG-PET, CT, PET
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-161991 (URN)10.1186/s40644-019-0237-1 (DOI)000477054900002 ()31337428 (PubMedID)
Available from: 2019-08-13 Created: 2019-08-13 Last updated: 2019-08-13Bibliographically approved
Edwinsdotter Ardnor, C., Rosén, A., Ljuslinder, I. & Melin, B. S. (2019). The BRCA1 exon 13 duplication: clinical characteristics of 22 families in Northern Sweden. Familial Cancer, 18(1), 37-42
Open this publication in new window or tab >>The BRCA1 exon 13 duplication: clinical characteristics of 22 families in Northern Sweden
2019 (English)In: Familial Cancer, ISSN 1389-9600, E-ISSN 1573-7292, Vol. 18, no 1, p. 37-42Article in journal (Refereed) Published
Abstract [en]

The clinical management of BRCA1/2 mutation carriers requires accurate cancer risk estimates. Cancer risks vary according to type and location of the mutation and since there is limited information about mutation-specific cancer risks, genotype-phenotype correlation studies are needed. This is a report of 22 families with the same mutation, BRCA1 duplication exon 13, a mutation that is found world-wide, with the objective to describe the cancer history found in these families. We studied 69 confirmed carriers, 53 women and 16 men, and additionally 29 women who were clinically expected carriers. Among the confirmed carriers, 27 women (51%) were diagnosed with breast cancer, 10 (19%) with ovarian cancer, 5 (9%) with breast and ovarian cancer and 17 (32%) without cancer. Nine women (17%) with breast cancer were 35 years or younger at diagnose. Also, two cases of early onset colon cancer were found, and 37,5% of the male carriers were diagnosed with prostate cancer. These data may have implications for risk assessment and cancer prevention decision making for carriers of the BRCA1 duplication exon 13 mutation.

Place, publisher, year, edition, pages
Springer, 2019
Keywords
BRCA1, BRCA1 ins6kbEx13, Breast cancer, Ovarian cancer, Prostate cancer, Colon cancer
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-155774 (URN)10.1007/s10689-018-0098-y (DOI)000455137200005 ()30136106 (PubMedID)
Funder
Västerbotten County Council
Available from: 2019-01-28 Created: 2019-01-28 Last updated: 2019-01-28Bibliographically approved
Lundberg, I., Wikberg, M. L., Ljuslinder, I., Li, X., Myte, R., Zingmark, C., . . . Palmqvist, R. (2018). MicroRNA expression in KRAS- and BRAF-mutated colorectal cancers. Anticancer Research, 38(2), 677-683
Open this publication in new window or tab >>MicroRNA expression in KRAS- and BRAF-mutated colorectal cancers
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2018 (English)In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 38, no 2, p. 677-683Article in journal (Refereed) Published
Abstract [en]

Background/Aim: KRAS and BRAF are two genes commonly mutated in colorectal cancer (CRC). Even though BRAF is a downstream target of KRAS in the MAPK signalling pathway, KRAS- and BRAF-mutated CRCs are found to display several different clinical and histopathological features. We investigated whether a differential expression of microRNAs (miRNAs) could explain the clinicopathological differences seen between KRAS-and BRAF-mutated CRCs.

Materials and Methods: Using a PCR array, we analyzed the expression of 84 different miRNAs in CRC cell lines wild-type in KRAS and BRAF, or mutated in KRAS or BRAF.

Results: Ten miRNAs were selected for further analyses in tumor tissue specimens (let-7a, let-7i, miR-10a, miR-10b, miR-31, miR-100, miR-181a, miR-181b, miR-372, and miR-373). BRAF-mutated tumors were found to express significantly higher levels of miR-31 as well as significantly lower levels of miR-373, compared to wild-type tumors.

Conclusion: Our results suggest that KRAS and BRAF-mutated CRCs may have different miRNA signatures compared to CRC tumors wild-type in KRAS and BRAF. However, no difference in expression levels between KRAS-and BRAF-mutated tumors was evident for the miRNAs analyzed in this study.

Place, publisher, year, edition, pages
International Institute of Anticancer Research, 2018
Keywords
colorectal cancer, miRNA, KRAS, BRAF, molecular subgroups
National Category
Cell and Molecular Biology Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-133409 (URN)10.21873/anticanres.12272 (DOI)000423315300010 ()29374690 (PubMedID)
Note

Originally included in thesis in manuscript form

Available from: 2017-04-10 Created: 2017-04-10 Last updated: 2018-06-09Bibliographically approved
Wikberg, M. L., Myte, R., Palmqvist, R., van Guelpen, B. & Ljuslinder, I. (2018). Plasma miRNA can detect colorectal cancer, but how early?. Cancer Medicine, 7(5), 1697-1705
Open this publication in new window or tab >>Plasma miRNA can detect colorectal cancer, but how early?
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2018 (English)In: Cancer Medicine, ISSN 2045-7634, E-ISSN 2045-7634, Vol. 7, no 5, p. 1697-1705Article in journal (Refereed) Published
Abstract [en]

Colorectal cancer (CRC) is a major cause of deaths worldwide but has a good prognosis if detected early. The need for efficient, preferable non‐ or minimally invasive, inexpensive screening tools is therefore critical. We analyzed 12 miRNAs in pre‐ and postdiagnostic plasma samples to evaluate their potential as CRC screening markers. We used a unique study design with two overlapping cohorts, allowing analysis of pre‐ and postdiagnostic samples from 58 patients with CRC and matched healthy controls. Plasma concentrations of miR‐15b, ‐16, ‐18a, ‐19a, 21, ‐22, ‐25, ‐26a, ‐29c, ‐142‐5p, ‐150, and ‐192 were measured by semi‐quantitative real‐time PCR. Concentrations of miR‐18a, ‐21, ‐22, and ‐25 in plasma from patients with CRC were significantly altered compared to healthy controls. Combined as a multimarker panel, they detected CRC with an AUC of 0.93. Furthermore, levels of these three miRNAs also showed different levels in the prediagnostic case samples close to diagnosis. Only miR‐21‐levels were elevated several years before diagnosis. Plasma levels of miR‐18a, ‐21, ‐22, and ‐25 show promise as screening biomarkers for CRC. However, based on our unique analysis of prediagnostic and postdiagnostic samples from the same patients, we conclude that circulating miRNAs elevated at diagnosis may not automatically be suitable for CRC screening, if the increase occurs too close to clinical diagnosis.

Place, publisher, year, edition, pages
John Wiley & Sons, 2018
Keywords
Colorectal cancer, early detection, plasma miRNA
National Category
Clinical Laboratory Medicine
Identifiers
urn:nbn:se:umu:diva-146758 (URN)10.1002/cam4.1398 (DOI)000431972900011 ()29573205 (PubMedID)2-s2.0-85044281770 (Scopus ID)
Available from: 2018-04-19 Created: 2018-04-19 Last updated: 2018-06-13Bibliographically approved
Glimelius, B., Melin, B., Enblad, G., Alafuzoff, I., Beskow, A., Ahlström, H., . . . Sjöblom, T. (2018). U-CAN: a prospective longitudinal collection of biomaterials and clinical information from adult cancer patients in Sweden. Acta Oncologica, 57(2), 187-194
Open this publication in new window or tab >>U-CAN: a prospective longitudinal collection of biomaterials and clinical information from adult cancer patients in Sweden
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2018 (English)In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 57, no 2, p. 187-194Article in journal (Refereed) Published
Abstract [en]

Background: Progress in cancer biomarker discovery is dependent on access to high-quality biological materials and high-resolution clinical data from the same cases. To overcome current limitations, a systematic prospective longitudinal sampling of multidisciplinary clinical data, blood and tissue from cancer patients was therefore initiated in 2010 by Uppsala and Umea Universities and involving their corresponding University Hospitals, which are referral centers for one third of the Swedish population.

Material and Methods: Patients with cancer of selected types who are treated at one of the participating hospitals are eligible for inclusion. The healthcare-integrated sampling scheme encompasses clinical data, questionnaires, blood, fresh frozen and formalin-fixed paraffin-embedded tissue specimens, diagnostic slides and radiology bioimaging data.

Results: In this ongoing effort, 12,265 patients with brain tumors, breast cancers, colorectal cancers, gynecological cancers, hematological malignancies, lung cancers, neuroendocrine tumors or prostate cancers have been included until the end of 2016. From the 6914 patients included during the first five years, 98% were sampled for blood at diagnosis, 83% had paraffin-embedded and 58% had fresh frozen tissues collected. For Uppsala County, 55% of all cancer patients were included in the cohort.

Conclusions: Close collaboration between participating hospitals and universities enabled prospective, longitudinal biobanking of blood and tissues and collection of multidisciplinary clinical data from cancer patients in the U-CAN cohort. Here, we summarize the first five years of operations, present U-CAN as a highly valuable cohort that will contribute to enhanced cancer research and describe the procedures to access samples and data.

Place, publisher, year, edition, pages
Taylor & Francis, 2018
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-144850 (URN)10.1080/0284186X.2017.1337926 (DOI)000423473200003 ()28631533 (PubMedID)
Available from: 2018-02-23 Created: 2018-02-23 Last updated: 2018-06-09Bibliographically approved
Caini, S., Masala, G., Saieva, C., Kvaskoff, M., Sacerdote, C., Savoye, I., . . . Palli, D. (2017). Coffee, tea and melanoma risk: findings from the European Prospective Investigation into Cancer and Nutrition. International Journal of Cancer, 140(10), 2246-2255
Open this publication in new window or tab >>Coffee, tea and melanoma risk: findings from the European Prospective Investigation into Cancer and Nutrition
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2017 (English)In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 140, no 10, p. 2246-2255Article in journal (Refereed) Published
Abstract [en]

What's new? Laboratory studies suggest that coffee and tea protect against melanoma, but epidemiological findings are inconsistent. Here the authors studied more than 400,000 participants within the European Prospective Investigation into Cancer and Nutrition (EPIC) and confirmed an inverse association between caffeinated coffee consumption and melanoma risk. No association was found with decaffeinated coffee or tea. Interestingly, drinking coffee only protected men, but not women, from developing the often fatal skin cancer, raising interesting questions about gender-specific hormones or coffee habits influencing this association. In vitro and animal studies suggest that bioactive constituents of coffee and tea may have anticarcinogenic effects against cutaneous melanoma; however, epidemiological evidence is limited to date. We examined the relationships between coffee (total, caffeinated or decaffeinated) and tea consumption and risk of melanoma in the European Prospective Investigation into Cancer and Nutrition (EPIC). EPIC is a multicentre prospective study that enrolled over 500,000 participants aged 25-70 years from ten European countries in 1992-2000. Information on coffee and tea drinking was collected at baseline using validated country-specific dietary questionnaires. We used adjusted Cox proportional hazards regression models to calculate hazard ratios (HR) and 95% confidence intervals (95% CI) for the associations between coffee and tea consumption and melanoma risk. Overall, 2,712 melanoma cases were identified during a median follow-up of 14.9 years among 476,160 study participants. Consumption of caffeinated coffee was inversely associated with melanoma risk among men (HR for highest quartile of consumption vs. non-consumers 0.31, 95% CI 0.14-0.69) but not among women (HR 0.96, 95% CI 0.62-1.47). There were no statistically significant associations between consumption of decaffeinated coffee or tea and the risk of melanoma among both men and women. The consumption of caffeinated coffee was inversely associated with melanoma risk among men in this large cohort study. Further investigations are warranted to confirm our findings and clarify the possible role of caffeine and other coffee compounds in reducing the risk of melanoma.

National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-134695 (URN)10.1002/ijc.30659 (DOI)000399313200008 ()28218395 (PubMedID)
Available from: 2017-06-30 Created: 2017-06-30 Last updated: 2018-06-09Bibliographically approved
Chuang, S.-C., Boeing, H., Vollset, S. E., Midttun, O., Ueland, P. M., Bueno-de-Mesquita, B., . . . Aleksandrova, K. (2016). Cellular immune activity biomarker neopterin is associated hyperlipidemia: results from a large population-based study. Immunity & Ageing, 13, Article ID 5.
Open this publication in new window or tab >>Cellular immune activity biomarker neopterin is associated hyperlipidemia: results from a large population-based study
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2016 (English)In: Immunity & Ageing, ISSN 1742-4933, E-ISSN 1742-4933, Vol. 13, article id 5Article in journal (Refereed) Published
Abstract [en]

Background: Increased serum neopterin had been described in older age two decades ago. Neopterin is a biomarker of systemic adaptive immune activation that could be potentially implicated in metabolic syndrome (MetS). Measurements of waist circumference, triglycerides, high-density lipoprotein cholesterol (HDLC), systolic and diastolic blood pressure, glycated hemoglobin as components of MetS definition, and plasma total neopterin concentrations were performed in 594 participants recruited in the European Prospective Investigation into Cancer and Nutrition (EPIC).

Results: Higher total neopterin concentrations were associated with reduced HDLC (9.7 %, p < 0.01 for men and 9.2 %, p < 0.01 for women), whereas no association was observed with the rest of the MetS components as well as with MetS overall (per 10 nmol/L: OR = 1.42, 95 % CI = 0.85-2.39 for men and OR = 1.38, 95 % CI = 0.79-2.43).

Conclusions: These data suggest that high total neopterin concentrations are cross-sectionally associated with reduced HDLC, but not with overall MetS.

Keywords
Neopterin, Cell-mediated immunity, Metabolic syndrome
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-118392 (URN)10.1186/s12979-016-0059-y (DOI)000370838100001 ()
Available from: 2016-04-18 Created: 2016-03-18 Last updated: 2018-06-07Bibliographically approved
Aleksandrova, K., Chuang, S.-C., Boeing, H., Zuo, H., Tell, G. S., Pischon, T., . . . Vineis, P. (2015). A prospective study of the immune system activation biomarker neopterin and colorectal cancer risk. Journal of the National Cancer Institute, 107(4), Article ID djv010.
Open this publication in new window or tab >>A prospective study of the immune system activation biomarker neopterin and colorectal cancer risk
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2015 (English)In: Journal of the National Cancer Institute, ISSN 0027-8874, E-ISSN 1460-2105, Vol. 107, no 4, article id djv010Article in journal (Refereed) Published
Abstract [en]

Background: Neopterin may be relevant for colorectal cancer (CRC) development, as a biomarker of cellular immune activity exerting pleiotropic effects on cellular ageing, oxidative stress, and inflammation. So far, the association between prediagnostic neopterin and colon and rectal cancer risk has not been evaluated in human populations. Methods: A nested case-control study was conducted within the European Prospective Investigation into Cancer and Nutrition cohort using data on plasma concentrations of total neopterin (T-N, sum of neopterin and 7,8-dihydroneopterin) in 830 incident CRC case patients (561 colon and 269 rectal) matched within risk sets to 830 control participants. A subsequent replication study used data from the Hordaland Health Study, where 173 CRC case patients have been diagnosed among 6594 healthy participants over 12 years of follow-up. Results: After multivariable adjustment for a priori chosen CRC risk factors, a "U-shaped" association of T-N with CRC was revealed. Compared with the second quintile of the T-N distribution, the relative risks for the first, third, fourth, and fifth quintiles were 2.37 (95% CI = 1.66 to 3.39), 1.24 (95% CI = 0.87 to 1.77), 1.55 (95% CI = 1.08 to 2.22), and 2.31 (95% CI = 1.63 to 3.27), respectively. Replication of these associations within the Hordaland Health Study yielded similar results. No differences have been observed when the associations were explored by colon and rectal cancer site (two-sided P-difference = .87) and after excluding case patients diagnosed within the first four follow-up years. Conclusions: These novel findings provide evidence of the role of both suppressed and activated cell-mediated immunity as reflected by prediagnostic T-N concentrations in the development of CRC.

Place, publisher, year, edition, pages
Oxford University Press, 2015
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-105269 (URN)10.1093/jnci/djv010 (DOI)000355082500013 ()
Available from: 2015-06-22 Created: 2015-06-22 Last updated: 2018-06-07Bibliographically approved
Kreimer, A. R., Brennan, P., Kuhs, K. A. L., Waterboer, T., Clifford, G., Franceschi, S., . . . Johansson, M. (2015). Human Papillomavirus Antibodies and Future Risk of Anogenital Cancer: A Nested Case-Control Study in the European Prospective Investigation Into Cancer and Nutrition Study. Journal of Clinical Oncology, 33(8), 877-884
Open this publication in new window or tab >>Human Papillomavirus Antibodies and Future Risk of Anogenital Cancer: A Nested Case-Control Study in the European Prospective Investigation Into Cancer and Nutrition Study
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2015 (English)In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 33, no 8, p. 877-884Article in journal (Refereed) Published
Abstract [en]

Purpose Human papillomavirus (HPV) type 16 (HPV16) causes cancer at several anatomic sites. In the European Prospective Investigation Into Cancer and Nutrition study, HPV16 E6 seropositivity was present more than 10 years before oropharyngeal cancer diagnosis and was nearly absent in controls. The current study sought to evaluate the extent to which HPV16 E6 antibodies are present before diagnosis of anogenital cancers within the same cohort. Methods Four hundred incident anogenital cancers (273 cervical, 24 anal, 67 vulvar, 12 vaginal, and 24 penile cancers) with prediagnostic blood samples (collected on average 3 and 8 years before diagnosis for cervix and noncervix cancers, respectively) and 718 matched controls were included. Plasma was analyzed for antibodies against HPV16 E6 and multiple other HPV proteins and genotypes and evaluated in relation to risk using unconditional logistic regression. Results HPV16 E6 seropositivity was present in 29.2% of individuals (seven of 24 individuals) who later developed anal cancer compared with 0.6% of controls (four of 718 controls) who remained cancer free (odds ratio [OR], 75.9; 95% CI, 17.9 to 321). HPV16 E6 seropositivity was less common for cancers of the cervix (3.3%), vagina (8.3%), vulva (1.5%), and penis (8.3%). No associations were seen for non-type 16 HPV E6 antibodies, apart from anti-HPV58 E6 and anal cancer (OR, 6.8; 95% CI, 1.4 to 33.1). HPV16 E6 seropositivity tended to increase in blood samples drawn closer in time to cancer diagnosis. Conclusion HPV16 E6 seropositivity is relatively common before diagnosis of anal cancer but rare for other HPV-related anogenital cancers.

National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-106032 (URN)10.1200/JCO.2014.57.8435 (DOI)000356055600014 ()25667279 (PubMedID)
Available from: 2015-07-06 Created: 2015-07-03 Last updated: 2018-06-07Bibliographically approved
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ORCID iD: ORCID iD iconorcid.org/0000-0002-5046-1820

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