Sexual behaviour and papillomavirus exposure in cervical intraepithelial neoplasia: a population-based case-control study.

Kjellberg, Lennart; Wang, Z; Wiklund, Fredrik; Edlund, Karin; Angstr√∂m, T; Lenner, Per; Sj√∂berg, I; Hallmans, Göran; Wallin, Keng-Ling; Sapp, Martin; Schiller, John T.; Wadell, Göran; M√§hlck, C G; Dillner, Joakim

doi:10.1099/0022-1317-80-2-391

Cited by 82 publications

(57 citation statements)

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“…In a previous paper, we have found that HPV-infection explained this association and that sexual history per se thus was not a risk factor (Kjellberg et al, 1999). In this study we detected the well known association between early age of sexual debut and risk for CIN, but again this association lost significance after adjusting for HPV infection.…”

Section: Discussionsupporting

confidence: 56%

“…b Adjusted odds ratios for HPV seropositivity, smoking and age. c The data on number of lifetime sexual partners has also been published in Kjellberg et al (1999). in the reference category.…”

Section: Resultsmentioning

confidence: 99%

“…This is intended to allow distinguishing between cofactors independent of HPV (not affected by HPV adjustments), cofactors confounded by risk of HPV exposure (eliminated both by adjusting for HPV seropositivity and for HPV DNA) and cofactors that determine whether HPV is cleared or becomes persistent (eliminated by adjusting for HPV DNA, not affected by adjusting for HPV seropositivity). However, HPV seropositivity is not completely sensitive (estimated at 50-70% sensitivity; Kjellberg et al, 1999) and attenuation but not elimination of risks after adjusting for HPV seropositivity may also reflect residual confounding.…”

Section: Discussionmentioning

confidence: 99%

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Smoking, diet, pregnancy and oral contraceptive use as risk factors for cervical intra-epithelial neoplasia in relation to human papillomavirus infection

et al. 2000

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Smoking, nutrition, parity and oral contraceptive use have been reported as major environmental risk factors for cervical cancer. After the discovery of the very strong link between human papillomavirus (HPV) infection and cervical cancer, it is unclear whether the association of these environmental factors with cervical cancer reflect secondary associations attributable to confounding by HPV, if they are independent risk factors or whether they may act as cofactors to HPV infection in cervical carcinogenesis. To investigate this issue, we performed a population-based case–control study in the Västerbotten county of Northern Sweden of 137 women with high-grade cervical intra-epithelial neoplasia (CIN 2–3) and 253 healthy age-matched women. The women answered a 94-item questionnaire on diet, smoking, oral contraceptive use and sexual history and donated specimens for diagnosis of present HPV infection (nested polymerase chain reaction on cervical brush samples) and for past or present HPV infections (HPV seropositivity). The previously described protective effects of dietary micronutrients were not detected. Pregnancy appeared to be a risk factor in the multivariate analysis ( P < 0.0001). Prolonged oral contraceptive use and sexual history were associated with CIN 2–3 in univariate analysis, but these associations lost significance after taking HPV into account. Smoking was associated with CIN 2–3 (odds ratio (OR) 2.6, 95% confidence interval (CI) 1.7–4.0), the effect was dose-dependent ( P = 0.002) and the smoking-associated risk was not affected by adjusting for HPV, neither when adjusting for HPV DNA (OR 2.5, CI 1.3–4.9) nor when adjusting for HPV seropositivity (OR 3.0, CI 1.9–4.7). In conclusion, after taking HPV into account, smoking appeared to be the most significant environmental risk factor for cervical neoplasia. © 2000 Cancer Research Campaign

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Section: Discussionsupporting

confidence: 56%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Smoking, diet, pregnancy and oral contraceptive use as risk factors for cervical intra-epithelial neoplasia in relation to human papillomavirus infection

et al. 2000

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“…However, a series of validation studies have concluded that only about 50 -70% of genitally infected women (as determined by PCR) will seroconvert (Kirnbauer et al, 1994;Carter et al, 1996;Kjellberg et al, 1999). The reason why HPV serology is not very sensitive for detection of HPV infection is not known.…”

Section: Discussionmentioning

confidence: 99%

A prospective study of the relationship between prediagnostic Human Papillomavirus seropositivity and HPV DNA in subsequent cervical carcinomas

et al. 2002

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Several prospective studies with invasive carcinoma as endpoint have supported Human Papillomavirus as a cause of cervical carcinoma. However, the largest study used seroepidemiology and did not analyse presence of Human Papillomavirus DNA in the subsequent tumour. Linkage of serum bank registries and cancer registries had identified 196 women with a registered cervical carcinoma after donation of a serum sample. For the present study, biopsies for 127 cases could be located, verified to contain invasive carcinoma and be amplified by PCR. Three control women who had remained alive and without cervical carcinoma during an equal length of follow-up had been matched to each of the case women and tested for HPV antibodies. Presence of Human Papillomavirus DNA in the tumours was analysed by general primer and type specific PCR. HPV16-seropositive women had a relative risk of 4.4 (95% CI: 2.2 -8.8) to develop cervical carcinoma carrying HPV16 DNA. By contrast, there was no excess risk for Human Papillomavirus 16-seropositive women to develop cervical carcinoma devoid of HPV16 DNA. Prediagnostic HPV16 seropositivity was strongly correlated with later HPV16 DNA positivity of the tumour (P50.001) and prediagnostic HPV18 seropositivity correlated with HPV18 DNA in the tumour (P50.03). The link between prediagnostic seropositivity and type of viral DNA in the cancer implies that the carcinogenic effect of infection with these viruses is dependent on persistent presence of type-specific viral DNA. The most important risk factor for development of cervical carcinoma is infection with the oncogenic types of human papillomavirus (HPV). A series of cross-sectional case-control studies, based both on HPV DNA testing of tumours (Walboomers et al, 1999), measurement of serum HPV antibodies (Dillner et al, 1995), or both (Nonnenmacher et al, 1995;de Sanjose et al, 1996) have found a consistent and strong association between HPV and cervical carcinoma.That the association between HPV and cervical carcinoma is causal is supported also by prospective studies, both with cervical intraepithelial neoplasia (Koutsky et al, 1992;Chua et al, 1996) and invasive cervical carcinoma as the end-point Shah et al, 1997;Vonka et al, 1999;Wallin et al, 1999). However, most prospective studies are based on limited numbers of cases. The largest study to date is a seroepidemiological study that contained 182 cases (Dillner et al, 1997). However, prediagnostic seropositivity and type of HPV DNA in subsequently occurring invasive carcinoma has not been previously performed. Combining seroepidemiological studies with HPV DNA analyses in prospective studies could be important for several reasons. For example, there are indications that prior or ongoing HPV infections may interact in a complex fashion in cervical carcinogenesis (Luostarinen et al, 1999;Silins et al, 1999). By comparing prediagnostic assessment of virus exposure with presence of virus DNA in the tumour, it could be possible to infer whether type-specific persistence of HPV is the predominant...

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“…A serum panel containing serum from 63 children with a mean age of 1.5 years (af Geijersstam et al, 1999) was analysed as a negative control. Samples from 71 adult women, with a mean age of 43 years and with limited sexual experience (70 women with one lifetime sexual partner and one woman with no lifetime sexual partners) were also analysed as negative controls (Kjellberg et al, 1999). After the method was established and validated, 208 serum samples from a nested case-control study of cervical cancer (Lehtinen et al, 1996) were analysed.…”

mentioning

confidence: 99%

Validation of multiplexed human papillomavirus serology using pseudovirions bound to heparin-coated beads

Faust

Knekt

Forslund

et al. 2010

Journal of General Virology

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This study developed and validated a high-throughput human papillomavirus (HPV) serology method based on Luminex technology, using pseudovirions (PsVs) of eight mucosal HPV types and two cutaneous HPV types bound to heparin-coated beads. Analysis with neutralizing type-specific monoclonal antibodies against the included HPV types indicated the type specificity of the assay. Analysis of negativecontrol serum samples from 63 children and 71 middle-aged women with up to one lifetime sexual partner indicated high specificity. Positive-control serum samples from subjects with known HPV DNA status or clinical diagnosis found expected sensitivities for most of the HPV types in 219 European serum samples, but lower than expected in 124 samples from Africa. HPV-45 and -52 did not react as expected with the human serum samples. The PsV-Luminex method was used to determine the HPV-seropositivity-associated relative risk for future cervical cancer using 208 serum samples from a prospective study of 18 814 women followed for 23 years, analysed previously with standard HPV-16 ELISA. The PsV-Luminex method gave similar results to ELISA (k50.77). As expected, HPV seropositivities assayed using the PsV-Luminex method found an increased risk of cervical cancer for HPV-16 [odds ratio (OR)57.7, 95 % confidence interval (CI)52.6-23] and HPV-31 (OR54.1, 95 % CI51.6-10.8), non-significant tendencies for increased risk for other mucosal HPV types and no risk for the cutaneous HPV types. In summary, multiplexed HPV serology using mammalian-derived PsVs selected for native conformation by binding to heparin-coated beads was validated as a high-throughput HPV serological method for most of the analysed HPV types. INTRODUCTIONGenital human papillomavirus (HPV) infections are the most common viral sexually transmitted diseases worldwide and are the main aetiological factors in cervical cancer development (Schiffman et al., 1993;Walboomers et al., 1999). HPV serology is important in HPV vaccinology and for analysis of past and present HPV infections, as persisting serum antibodies to the major capsid L1 protein develop in the majority of infected subjects (Wang et al., 1996). Most HPV infections are cleared spontaneously, but among a small subset of infected individuals HPV persists and can cause malignancies (Schiffman et al., 1993). Because most HPV infections clear within 2 years, current infections detected by DNA analysis are only a minor part of all HPV exposures (Ho et al., 1995). HPV serology is also a valuable tool to study immune status prior to and after HPV vaccination (Harper et al., 2004;Koutsky et al., 2002), as antibodies against HPV virus-like particles (VLPs) mediate protective immunity, at least in animalmodel systems (Arbyn & Dillner, 2007).HPV VLPs are formed spontaneously after overexpressing the L1 protein in variety of expression systems (Hagensee et al., 1993;Kirnbauer et al., 1992;Le Cann et al., 1994;Sasagawa et al., 1995). Production of VLPs is demanding, and stability, yield and correct conformation are common ...

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Sexual behaviour and papillomavirus exposure in cervical intraepithelial neoplasia: a population-based case-control study.

Abstract: Sexual history is an established risk determinant for cervical neoplasia. It is not clear if human papillomavirus (HPV

Cited by 82 publications

References 37 publications

Smoking, diet, pregnancy and oral contraceptive use as risk factors for cervical intra-epithelial neoplasia in relation to human papillomavirus infection

Smoking, diet, pregnancy and oral contraceptive use as risk factors for cervical intra-epithelial neoplasia in relation to human papillomavirus infection

A prospective study of the relationship between prediagnostic Human Papillomavirus seropositivity and HPV DNA in subsequent cervical carcinomas

Validation of multiplexed human papillomavirus serology using pseudovirions bound to heparin-coated beads

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