Association of Serum Immunoglobulin G Antibodies Against Human Papillomavirus Type 16 Capsids With Anal Epidermoid Carcinoma

Heino, Pirkko; Eklund, Carina; Fredriksson-Shanazarian, Vanoohi; Goldman, Sven; Schiller, John T.; Dillner, Joakim

doi:10.1093/jnci/87.6.437

Cited by 57 publications

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“…By applying HPV serology, a marker of both past and present HPV infection, it has been possible to investigate possible temporal associations of HPV infection with anal cancer. Previously, a serologic association of HPV 16 with incident anal cancer has been reported (Heino et al, 1995). In our previous, prospective study, no association of HPV and anal cancer was found, although a high, but insignificant risk was found for perianal skin cancer (Bjørge et al, 1997a).…”

Section: Discussionmentioning

confidence: 69%

“…A serologic association of HPV 16 with incident anal cancer has been shown (Heino et al, 1995). In a study of the role of HPV in non-cervical anogenital cancers, we found that HPV 16 seropositivity conferred an increased risk for noncervical anogenital cancers, but not for anal cancer (Bjørge et al, 1997a).…”

mentioning

confidence: 58%

“…Seropositivity to HPV capsids was determined by an established and validated enzyme linked immunosorbent assay (ELISA) using baculovirus expressed capsids comprising both the L1 and L2 proteins, with disrupted capsids of bovine papillomavirus as control (Heino et al, 1995). The cut-off levels used to assign seropositivity were preassigned and, relative to internal standards, identical to the cut-offs used in previous studies (HPV 16: cutoff level 354, HPV 18, 33 and 73: cut-off level 100) (Bjørge et al, 1997a,b;Dillner et al, 1997).…”

Section: Laboratory Methodsmentioning

confidence: 99%

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Human papillomavirus infection as a risk factor for anal and perianal skin cancer in a prospective study

et al. 2002

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Human papillomavirus has emerged as the leading infectious cause of cervical and other anogenital cancers. We have studied the relation between human papillomavirus infection and the subsequent risk of anal and perianal skin cancer. A case -cohort study within two large Nordic serum banks to which about 760 000 individuals had donated serum samples was performed. Subjects who developed anal and perianal skin cancer during follow up (median time of 10 years) were identified by registry linkage with the nationwide cancer registries in Finland and Norway. Twenty-eight cases and 1500 controls were analysed for the presence of IgG antibodies to HPV 16, 18, 33 or 73, and odds ratios of developing anal and perianal skin cancer were calculated. There was an increased risk of developing anal and perianal skin cancer among subjects seropositive for HPV 16 (OR=3.0; 95%CI=1.1 -8.2) and HPV 18 (OR=4.4; 95%CI=1.1 -17). The highest risks were seen for HPV 16 seropositive patients above the age of 45 years at serum sampling and for patients with a lag time of less than 10 years. This study provides prospective epidemiological evidence of an association between infection with HPV 16 and 18 and anal and perianal skin cancer. Anal epidermoid carcinoma is a rare tumour, but its incidence has increased over the past 30 years (Goldman et al, 1989;Frisch et al, 1993;Melbye et al, 1994). Sexual behaviour and smoking are risk factors (Daling et al, 1992;Frisch et al, 1997). A high proportion of anal tumours are associated with human papillomavirus (HPV) infection (Melbye and Frisch, 1998). HPV 16 DNA has been reported in up to 93% of invasive squamous anal tumours and 69% of anal carcinoma in situ (Tilston, 1997).Most epidemiological studies on HPV infection and anal cancer have been case -series and case -control studies using samples taken after the cancer has been diagnosed. Such studies may be subject to differential misclassification related to the presence of the disease, and provide no information on the temporal order of events. Prospective studies are generally considered crucial for causality inference. As primary prevention of HPV infection by vaccination is being evaluated, it is important to establish which cancers are likely to be amenable to prevention. Prospective seroepidemiological studies have linked HPV to vulvar, vaginal and to a subset of head and neck cancers (Bjørge et al, 1997a;Mork et al, 2001).HPV serology, using capsids of HPV 16, 18 and 33, has been validated as a type-restricted marker of past or present HPV infection (Dillner, 1999). A serologic association of HPV 16 with incident anal cancer has been shown (Heino et al, 1995). In a study of the role of HPV in non-cervical anogenital cancers, we found that HPV 16 seropositivity conferred an increased risk for noncervical anogenital cancers, but not for anal cancer (Bjørge et al, 1997a). This was in spite of the fact that the proportion of anal cancer cases (25%) being HPV 16 seropositive was higher than for other non-cervical anogenital cancers (24%). This...

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Section: Discussionmentioning

confidence: 69%

mentioning

confidence: 58%

Section: Laboratory Methodsmentioning

confidence: 99%

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Human papillomavirus infection as a risk factor for anal and perianal skin cancer in a prospective study

et al. 2002

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“…The majority of the assays undertaken by participants were direct EIAs, involving coating EIA plates with VLPs whereas others used capture assays. 2,[11][12][13][14][15][16][17] One participant used an RIA 1 and the remaining laboratories EIAs. One participant used bacterially expressed and affinity-purified L1 capsid proteins fused to glutathione S-transferase as antigens.…”

Section: Assay Methodsmentioning

confidence: 99%

“…Eligible women first donated a 10 ml serum sample that was screened for presence of HPV antibodies by a standard ELISA in 1 laboratory, as described previously. 11 A negative control serum sample was collected from an adult woman who had reported no sexual experience and a positive control serum sample from a woman with >4 lifetime sexual partners who had been seropositive for antibody to capsids of HPV 6,11,16 and 18 in the initial screening. In all, 16 women were selected and donated blood for inclusion in the study.…”

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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Human papillomavirus antibody responses among patients with incident cervical carcinoma

et al. 1997

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The human papillomavirus (HPV) is recognized as a major cause of cervical cancer precursor lesions. HPV serology is a key method in the continuing elucidation of the importance of HPV exposure for cancer development and in predicting HPV-associated diseases. To extend previous HPV serological studies on cervical cancer, serum samples from a consecutive series of 216 women with incident untreated cervical carcinoma and 243 age- and sex-matched healthy blood donors were evaluated for the presence of antibodies against HPV capsids, a marker of past or present HPV exposure, as well as against several cervical cancer-associated defined HPV epitopes. Among the capsid antibody responses, HPV type 16 seropositivity had the strongest association with cervical cancer (OR 2.7, 95% CI 1.8-4.2), but HPV 18 and HPV 33 seropositivities were also significantly associated with cervical cancer (OR 1.6, 95% CI 1.1-2.5; and OR 1.5, 95% CI 1.0-2.2, respectively). The antibody responses against the defined HPV epitopes were confirmed to be associated with cervical cancer, at ORs ranging from 1.4 to 2.0. In conclusion, the study confirms that antibodies against defined HPV epitopes are associated with cervical cancer and provides evidence that seropositivities for HPV types 16, 18, and 33 are associated with cervical cancer risk.

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Association of Serum Immunoglobulin G Antibodies Against Human Papillomavirus Type 16 Capsids With Anal Epidermoid Carcinoma

Abstract: Exposure to HPV16 or related viruses appears to be a major risk factor in the majority of anal cancers.

Cited by 57 publications

References 0 publications

Human papillomavirus infection as a risk factor for anal and perianal skin cancer in a prospective study

Human papillomavirus infection as a risk factor for anal and perianal skin cancer in a prospective study

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

Human papillomavirus antibody responses among patients with incident cervical carcinoma

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