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  • 1
    Abstract: BACKGROUND: In addition to HPV, high parity and hormonal contraceptives have been associated with cervical cancer (CC). However, most of the evidence comes from retrospective case-control studies. The aim of this study is to prospectively evaluate associations between hormonal factors and risk of developing cervical intraepithelial neoplasia grade 3 (CIN3)/carcinoma in situ (CIS) and invasive cervical cancer (ICC). METHODS AND FINDINGS: We followed a cohort of 308,036 women recruited in the European Prospective Investigation into Cancer and Nutrition (EPIC) Study. At enrollment, participants completed a questionnaire and provided serum. After a 9-year median follow-up, 261 ICC and 804 CIN3/CIS cases were reported. In a nested case-control study, the 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 and Human herpesvirus 2. Multivariate analyses were performed to estimate hazard ratios (HR), odds ratios (OR) and corresponding 95% confidence intervals (CI). The cohort analysis showed that number of full-term pregnancies was positively associated with CIN3/CIS risk (p-trend = 0.03). Duration of oral contraceptives use was associated with a significantly increased risk of both CIN3/CIS and ICC (HR = 1.6 and HR = 1.8 respectively for 〉/=15 years versus never use). Ever use of menopausal hormone therapy was associated with a reduced risk of ICC (HR = 0.5, 95%CI: 0.4-0.8). A non-significant reduced risk of ICC with ever use of intrauterine devices (IUD) was found in the nested case-control analysis (OR = 0.6). Analyses restricted to all cases and HPV seropositive controls yielded similar results, revealing a significant inverse association with IUD for combined CIN3/CIS and ICC (OR = 0.7). CONCLUSIONS: Even though HPV is the necessary cause of CC, our results suggest that several hormonal factors are risk factors for cervical carcinogenesis. Adherence to current cervical cancer screening guidelines should minimize the increased risk of CC associated with these hormonal risk factors.
    Type of Publication: Journal article published
    PubMed ID: 26808155
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  • 2
    Keywords: CANCER ; RISK ; RESPONSES ; antibodies ; NESTED CASE-CONTROL ; EARLY PROTEINS ; glutathione-S-transferase ; CELL-CARCINOMA ; human polyomaviruses ; CHLAMYDIA-TRACHOMATIS INFECTION
    Abstract: To evaluate prospectively the association between serological markers of selected infections, including HPV, and risk of developing cervical cancer (CC) and precancer, we performed a nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) study that included 184 cases of invasive CC (ICC), 425 cases of cervical intraepithelial neoplasia (CIN) grade 3 or carcinoma in situ (CIS), and 1,218 matched control women. At enrollment participants completed lifestyle questionnaires and provided sera. Subjects were followed-up for a median of 9 years. Immunoassays were used to detect serum antibodies to Human Herpes Virus 2 (HHV-2), Chlamydia trachomatis (CT), Chlamydia pneumoniae, L1 proteins of mucosal and cutaneous HPV types, E6/E7 proteins of HPV16/18, as well as to four polyomaviruses. Adjusted odds ratios (OR) [and 95% confidence intervals (CI)] for CIN3/CIS and ICC risk were respectively: 1.6 (1.2-2.0) and 1.8 (1.1-2.7) for L1 seropositivity to any mucosal HPV type, 1.0 (0.4-2.4) and 7.4 (2.8-19.7) for E6 seropositivity to HPV16/18, 1.3 (0.9-1.9) and 2.3 (1.3-4.1) for CT seropositivity, and 1.4 (1.0-2.0) and 1.5 (0.9-2.6) for HHV-2 seropositivity. The highest OR for ICC was observed for HPV16 E6 seropositivity [OR=10.2 (3.3-31.1)]. Increasing number of sexually transmitted infections (STIs) was associated with increasing risk. Non-STIs were not associated with CC risk. In conclusion, this large prospective study confirms the important role of HPV and a possible contribution of CT and HHV-2 in cervical carcinogenesis. It further identifies HPV16 E6 seropositivity as the strongest marker to predict ICC well before disease development. What's New? Limited data are available from prospective studies concerning the role of past exposure to human papillomavirus (HPV) and other infections in cervical carcinogenesis. This study assessed associations between cervical cancer and pre-cancer and serological markers of exposure to mucosal and cutaneous HPVs, Chlamydia trachomatis (CT), Chlamydia pneumonia, human herpes virus-2 (HHV-2), and polyomaviruses using a nested case-control design within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Associations were found for mucosal HPVs, CT, and HHV-2. A greater number of sexually transmitted diseases further raised the risk of cervical cancer.
    Type of Publication: Journal article published
    PubMed ID: 24338606
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  • 3
    Keywords: CIGARETTE-SMOKING ; intraepithelial neoplasia ; TOBACCO SMOKING ; glutathione-S-transferase ; ORAL-CONTRACEPTIVE USE ; pooled analysis ; COLLABORATIVE REANALYSIS ; PASSIVE SMOKING ; INDIVIDUAL DATA ; ONCOGENIC HUMAN-PAPILLOMAVIRUS
    Abstract: 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. What's new? Tobacco smoking is a cited cause of cervical cancer, but whether it causes cervical malignancy independent of human papillomavirus (HPV) infection is unclear. Here, strong associations were found between most measures of tobacco smoking and the risk of cervical intraepithelial neoplasia of grade 3/carcinoma in situ and invasive cervical cancer, after taking into account past exposure to HPV infection. Quitting smoking was associated with a 2-fold risk reduction. The findings confirm the role of tobacco smoking in cervical carci
    Type of Publication: Journal article published
    PubMed ID: 24338632
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  • 4
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Summary We assessed the polymerase chain reaction (PCR) technique to detect Mycobacterium tuberculosis complex DNA In 48 paraffin-embedded specimens from 32 patients with different variants of cuttineous tuberculosis, and compared the resuts with those of culture. A 123 bp product of the 1S6110 insertion sequence specific of M. tuberculosis complex was amplified and confirmed by digestion with Sall restriction endonuclease. The time required for the procedure was 3 days. Thirty-seven samples (77.1%) were positive for M. tuberculosis complex DNA. No false positive results were obtained in nine negative controls, Of the 20 specimens tested by PCR and culture, the frequency of positivity was 90% for DNA amplification and 65% for culture. In seven cases of lupus vulgaris, the figures were 100% and 57% respectivety. In the 11 specimens culture negative or not microbiologically tesled and PCR negative, evidence for tuberculous infection was provided hy the correlation of various relative fmd absolute criteria. These results show that PCR amplification of the IS6110 insertion fragment is a rapid and accurate means for the detection of M. tuberculosis complex DNA in paraffin-embedded skin biopsies from patients with cutaneous tuberculosis, especially in paucibacillary lesions.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1365-2230
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: We describe a tuberculin test (PPD) negative patient with a chronic cutaneous lesion with histological features resembling sareoidosis, in whom M. tuberculosis complex DNA was detected in formalin-fixed paraffin-embedded tissue by polymerase chain reaction (PCR) amplification. The lesion cleared with antituberculous treatment.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1600-0560
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The histopathological changes observed in the cutaneous rash of three patients who suffered the acute phase of HFV infection are described. In all three patients a perivascular and interstitial inflammatory infiltrate was present in the upper and mid-reticular dermis. In one biopsy isolated areas of epidermal necrosis were observed and in the two other biopsies a perifollicular inflammatory infiltrate was detected with perforation in one case. Furthermore, a periductal infiltrate was observed in one of these biopsies.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Suite 500, 5th Floor, 238 Main Street, Cambridge, Massachusetts, 02142, USA : Blackwell Science Inc.
    ISSN: 1525-1438
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: DNA content was related to the type of human papillomaviruses (HPV) in a series of 87 lesions of the lower female genital tract. Nineteen condylomas, 32 biopsies with slight dysplasia, 19 with moderate dysplasia and 17 with severe dysplasia-carcinoma in situ were studied. HPV status was assessed by in situ hybrization (ISH) with biotinylated probes (HPV 6/11, 16/18, 31/35/51) and the polymerase chain reaction (PCR) (HPV 16,18). DNA ploidy was measured by Feulgen DNA cytophotometry. Positivity for HPV by ISH and PCR was obtained in 48% and 59% of the biopsies, respectively. Seventy-eight per cent of the lesions were diploid or tetraploid and the remaining 22% were aneuploid. The percentage of aneuploid DNA increased with the severity of the lesions. By comparing DNA-ploidy and HPV types by ISH, diploid DNA was more frequently found in HPV 6/11 positive lesions (93%) than in HPV 16/18 positive (81%) or HPV 31/35/51 positive (57%). PCR was more sensitive for detecting HPV in aneuploid dysplastic lesions than ISH, probably indicating the HPV copies are scarce in such lesions. In summary, the results indicate some relationship between aneuploidy and HPV types 16/18 and 31/35/51, which supports an oncogenic potential of these subtypes of HPV.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1435-4373
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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