Comparison of Development of Serum Antibodies to HPV16 and HPV33 and Acquisition of Cervical HPV DNA Among Sexually Experienced and Virginal Young Girls

Andersson-Ellström, Agneta; Dillner, Joakim; Hagmar, Björn; Schiller, John T.; Sapp, Martin; Forssman, Lars; Milsom, Ian

doi:10.1097/00007435-199605000-00013

Cited by 87 publications

(49 citation statements)

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“…Some of the previous studies found considerable variation in the association between HPV 16 exposure and the risk of ESCC when they changed their cutpoints. 9,10 For example, in Bjorge's study 9 the OR for the association of HPV 16 and ESCC changed from 10 for a cutpoint of 0.239 (a level that that had given optimal discrimination of cases and controls in a previous study 27 ) to 2.3 for a cutpoint of 0.100 (a level that distinguishes HPV 16 infected women from sexually inexperienced women 28 ). To overcome this problem, we examined graphs of risk versus type-specific log OD produced by cubic spline logistic regressions and defined a spline cutpoint as the inflection point beyond which the graph either monotonically increased or decreased.…”

Section: Discussionmentioning

confidence: 99%

Human papillomavirus serology and the risk of esophageal and gastric cancers: Results from a cohort in a high‐risk region in China

Kamangar

Qiao

Schiller

et al. 2006

Intl Journal of Cancer

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Each year, esophageal and gastric cancers cause more than 900,000 deaths worldwide. Human papilloma virus (HPV), especially type 16, has been suggested to have a role in the etiology of esophageal cancer, however, the results of previous seroepidemiological studies have not been consistent. We conducted a large prospective study to examine the association between serum antibodies to HPV 16, HPV 18 and HPV 73 and subsequent development of esophageal squamous cell carcinoma (ESCC), gastric cardia adenocarcinoma (GCA), and gastric noncardia adenocarcinoma (GNCA) in a high-risk population for these cancers in Linxian, China. Case and control subjects for this study were selected from the 29,584 participants of the Linxian General Population Trial. Prediagnostic serum samples from 99 cases of ESCC, 100 cases of GCA, 70 cases of GNCA, and 381 age-and sex-matched controls were selected for this study. The presence of antibodies to HPV virus-like particles was determined by type-specific enzyme-linked immunosorbent assays. Fewer than 15% of ESCC, GCA, or GNCA cases were positive for each HPV type, and no significant associations were found. The adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) for HPV 16 seropositivity and ESCC, GCA, and GNCA risk were 1.6 (0.8-3.3), 1.3 (0.6-2.8) and 0.4 (0.1-1.6), respectively. The comparable ORs (95% CIs) for HPV 18 were 1.0 (0.4-2.2), 0.9 (0.4-2.1) and 1.5 (0.6-3.4). For HPV 73, these figures were 1.3 (0.6-2.5), 1.2 (0.6-2.3) and 0.9 (0.4-2.1). The results of this study do not support a major role for HPV 16, HPV 18 and HPV 73 in the etiology of esophageal and gastric cancers in Linxian, China. ' 2006 Wiley-Liss, Inc.Key words: esophageal cancer; human papillomavirus; serology Oncogenic types of human papillomavirus (HPV), most notably HPV 16 and HPV 18, are recognized as the most significant risk factors for cervical cancer. 1 The role of HPV in the etiology of cancers of vulva, anus, penis and oropharyngeal cavity has also been established. 2 The role of HPV in the etiology of esophageal cancer, however, remains controversial. Syrjanen first suggested a role for HPV in the etiology of esophageal squamous cell carcinoma (ESCC) in 1982, based on observing characteristic histological findings suggesting the presence of HPV in benign esophageal epithelia and malignant esophageal tumors. 3 During the past 20 years, several studies have used a variety of techniques, including detection of HPV DNA in esophageal tumor tissues and serologic methods, to examine the association between exposure to HPV and risk of ESCC. 4 The results of HPV DNA studies have not been consistent: case series using polymerase chain reaction (PCR) have found evidence for the presence of HPV in the tumor tissues varying from 0 to 67%. 4 Type-restricted serologic assays for different HPV types using virus-like particles were first developed in the mid-1990s, 5 and were subsequently shown to be relatively specific for each HPV type. 6 Seroreactivity to HPV 16 is a strong marker of continuous past exp...

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Section: Discussionmentioning

confidence: 99%

Human papillomavirus serology and the risk of esophageal and gastric cancers: Results from a cohort in a high‐risk region in China

Kamangar

Qiao

Schiller

et al. 2006

Intl Journal of Cancer

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“…Discrepancies were resolved by multiple repeat analyses. A panel of serum samples from virginal women was analysed in parallel and no HPV antibodies could be found (Andersson-Ellström et al, 1996).…”

Section: Hpv Serologymentioning

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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“…Serum samples from HPV infected women were selected from 3 previously described population-based epidemiological studies of HPV infection, [8][9][10] where the cohorts were still followed. To maximize the probability of obtaining sera reactive with only 1 HPV genotype, sera were selected where sample donors had indicated that they had had only 1 lifetime sexual partner, although 1 donor who had reported 2-3 partners was also included.…”

Section: Study Samplesmentioning

confidence: 99%

Results of the first WHO international collaborative study on the standardization of the detection of antibodies to human papillomaviruses

et al. 2005

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Detection of genotype-specific human papillomavirus (HPV) capsid antibody in serum suggests past HPV infection. Also, these antibodies appear to correlate with vaccine-induced protection against infection, at least in animal models. However, each laboratory defines a reactive result differently and there is no agreed definition of what level of response indicates sero-reactivity. Standardization of assays for HPV capsid antibody will therefore assist with HPV vaccine development and epidemiology. This study was undertaken to investigate the specificity and sensitivity of assays in current use for measuring antibody to the major viral capsid protein L1 of HPV. Ten laboratories from 8 countries each analyzed 12 coded serum samples, which were derived from an uninfected woman, from naturally infected women and from individuals immunized with different vaccine candidates currently under clinical development. Study samples were assayed by methods in routine use in the participating laboratories. Nine assays were based on virus-like particles (VLPs) of 1 or more HPV genotypes. One laboratory used bacterially expressed major capsid protein L1 of HPV genotypes as antigen. There was considerable interlaboratory variation in estimated antibody levels. However, ranking of the potency of HPV 16 reactivity across the 12 test sera was consistent for all 10 laboratories. Expression of HPV 16 antibody levels relative to that of a single serum sample from an HPV16-infected woman considerably improved the interlaboratory assay comparability. Establishment of an International Standard for antibodies to HPV 16 would therefore facilitate the comparison of HPV antibody measurements between laboratories and assays. ' 2005 Wiley-Liss, Inc.Key words: human papilloma virus; VLPs; standardization; antibody Several candidate vaccines against human papillomavirus (HPV), the major cause of cervical cancer, are under clinical development. These are designed to induce viral capsid-specific antibodies, which can neutralize infectious virus. HPV vaccine candidates are based on recombinant virus capsid proteins, so called virus-like particles (VLPs), and are designed to prevent infections by the most common oncogenic HPV types 16 and 18, 1-3 as well as against the common HPV types 6 and 11, which cause genital warts. 3 Vaccine-induced protection against infection with HPV is likely to be related to the induced level of HPV capsid neutralizing antibody. To date, neutralization assays appear to be mostly HPV genotype-specific, as are capsid-specific antibodies induced by HPV infection. 4 Furthermore, neutralizing antibody titers correlate with antibody titers detected in enzyme immunoassays (EIA). 4 International comparability of HPV antibody measurements will be crucial in defining an antibody correlate of protection and for monitoring whether the different HPV vaccine preparations induce strong and durable antibody responses in different populations. There are also increasing demands to standardize HPV serological methods as a measure of past or ...

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Comparison of Development of Serum Antibodies to HPV16 and HPV33 and Acquisition of Cervical HPV DNA Among Sexually Experienced and Virginal Young Girls

Abstract: Both HPV serology and HPV DNA testing indicated that the number of sexual partners and earliness of coitus debut determined the risk for acquiring HPV infection and that nonsexually transmitted infections are rare or nonexistent among adolescent girls.

Cited by 87 publications

References 23 publications

Human papillomavirus serology and the risk of esophageal and gastric cancers: Results from a cohort in a high‐risk region in China

Human papillomavirus serology and the risk of esophageal and gastric cancers: Results from a cohort in a high‐risk region in China

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

Results of the first WHO international collaborative study on the standardization of the detection of antibodies to human papillomaviruses

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