Human Papillomavirus Infection Is Transient in Young Women: A PopulationBased Cohort Study

Evander, Magnus; Edlund, Karin; Gustafsson, Åke; Jönsson, Malin; Karlsson, Roger; Rylander, Eva; Wadell, Göran

doi:10.1093/infdis/171.4.1026

Cited by 264 publications

(177 citation statements)

References 9 publications

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“…This could represent false negative HPV DNA tests due to old tissue samples or samples of bad quality. Since most of the HPV infections are transient (Hildesheim et al, 1994;Evander et al, 1995;Ho et al, 1998), another possibility is that after the infections with HPV 16, 18 and/or 33 have ceased, a history of HPV infection may still increase the risk for cervical carcinoma. However, as seropositive women were not at increased risk to develop carcinomas that were HPV-negative or containing other types of virus, our data strongly suggests that persistent type-specific HPV infection is required and that the HPV DNA-negative cases either really are HPV-negative or contain unknown HPV types that are not adequately amplified by the PCR tests used.…”

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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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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“…1 Genital infections with oncogenic HPV types are very common among sexually active women, but only a minority of infected women will have a persistent HPV infection. [2][3][4] Type-specific persistence of HPV (defined as repeated detectability of the same type of HPV DNA in serial samples) is a much stronger risk factor for high-grade CIN 5 and cervical cancer 6 than HPV infection per se.…”

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confidence: 99%

Chlamydia trachomatis infection and persistence of human papillomavirus

Silins

Ryd

Strand

et al. 2005

Intl Journal of Cancer

139

108

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Human papillomavirus (HPV) persistence is the major cause of cervical cancer, but most HPV infections will not persist and risk factors for HPV persistence are not well known. Chlamydia (C.) trachomatis infection seems to also be associated with cervical cancer. We investigated whether C. trachomatis infection is a risk factor for HPV persistence. In a cohort of 12,527 women participating in a population-based HPV screening trial in Sweden, 6,418 women completed testing for HPV DNA by general primer PCR and typing by reverse dot blot hybridization. On average 19 months later, 303 women that had been HPV-positive and had normal cytology at enrollment completed a new HPV test. Environmental exposures were assessed by an 87-item questionnaire. Previous sexually transmitted infections were also investigated by serology. At follow-up, 44% of the women were positive for the same type of HPV DNA as at enrollment. Persistence correlated with length of follow-up (p < 0.01) and condom use seemed to protect against HPV persistence (p < 0.05). The most significant risk factor for persistent presence of HPV DNA was self-reported history of previous C. trachomatis infection (relative risk in multivariate model = 2.09; 95% confidence interval = 1.05-4.18). We conclude that persistence of oncogenic HPV infections is more likely among women with a previous C. trachomatis infection. ' 2005 Wiley-Liss, Inc.Key words: HPV infection; HPV persistence; Chlamydia trachomatis; epidemiology Persistent oncogenic HPV infection is recognized as a necessary factor in development of high grade cervical intraepithelial neoplasia and invasive cervical cancer. 1 Genital infections with oncogenic HPV types are very common among sexually active women, but only a minority of infected women will have a persistent HPV infection. 2-4 Type-specific persistence of HPV (defined as repeated detectability of the same type of HPV DNA in serial samples) is a much stronger risk factor for high-grade CIN 5 and cervical cancer 6 than HPV infection per se.Chlamydia (C.) trachomatis has been found repeatedly to associate with cervical neoplasia and invasive cancer in cross-sectional case-control studies, 7,8 although the association has commonly been thought to be the result of confounding by HPV. During recent years, an association with C. trachomatis has also been found in several biobank-based longitudinal studies with invasive cervical cancer as endpoint. [9][10][11][12] The vexed question of whether the association could be due to confounding by HPV infection is, however, only possible to address in cohort studies comprising only HPV-infected women.A possible explanation for the association of C. trachomatis and cervical cancer might be that the C. trachomatis-induced inflammation results in an impaired ability to clear HPV infections.To investigate these issues, we carried out a prospective, population-based cohort study restricted to HPV-infected women with HPV persistence as the endpoint. Subjects and methods Study settingA population-based randomized mul...

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“…Genital infection with HPV is generally transient, with the majority of individuals showing clearance of the virus within 1 year of detection (Evander et al, 1995;Ho et al, 1998;Woodman et al, 2001;Sellors et al, 2003). In fact, only a minority of women develop persistent infections with focally high levels of HPV DNA, and only some of these progress to high-grade disease and invasive carcinoma (Herrero et al, 2000).…”

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confidence: 99%

T-cell responses to human papillomavirus type 16 among women with different grades of cervical neoplasia

et al. 2005

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Infection with high-risk genital human papillomavirus (HPV) types is a major risk factor for the development of cervical intraepithelial neoplasia (CIN) and invasive cervical carcinoma. The design of effective immunotherapies requires a greater understanding of how HPV-specific T-cell responses are involved in disease clearance and/or progression. Here, we have investigated T-cell responses to five HPV16 proteins (E6, E7, E4, L1 and L2) in women with CIN or cervical carcinoma directly ex vivo. T-cell responses were observed in the majority (78%) of samples. The frequency of CD4 þ responders was far lower among those with progressive disease, indicating that the CD4 þ T-cell response might be important in HPV clearance. CD8 þ reactivity to E6 peptides was dominant across all disease grades, inferring that E6-specific CD8 þ T cells are not vitally involved in disease clearance. T-cell responses were demonstrated in the majority (80%) of cervical cancer patients, but are obviously ineffective. Our study reveals significant differences in HPV16 immunity during progressive CIN. We conclude that the HPV-specific CD4 þ T-cell response should be an important consideration in immunotherapy design, which should aim to target preinvasive disease.

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Human Papillomavirus Infection Is Transient in Young Women: A PopulationBased Cohort Study

Cited by 264 publications

References 9 publications

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

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

Chlamydia trachomatis infection and persistence of human papillomavirus

T-cell responses to human papillomavirus type 16 among women with different grades of cervical neoplasia

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