0000000000021899
AUTHOR
John T. Schiller
Prospective seroepidemiologic study of human papillomavirus infection as a risk factor for invasive cervical cancer
Background: Major risk factors for invasive cervical cancer include infection with human papillomavirus (HPV), infection with other sexually transmitted pathogens (e.g., Chlamydia trachomatis), and smoking. Since exposures to these risk factors can be related, the contribution of any single factor to cervical carcinogenesis has been difficult to assess. We conducted a prospective study to define the role of HPV infection in cervical carcinogenesis, with invasive cancer as an end point. Methods: A nested case‐control study within a joint cohort of 700 000 Nordic subjects was performed. The 182 women who developed invasive cervical cancer during a mean follow-up of 5 years were matched with 5…
A prospective study on the risk of cervical intra-epithelial neoplasia among healthy subjects with serum antibodies to HPV compared with HPV DNA in cervical smears
To estimate the risk of developing cervical intra-epithelial neoplasia (CIN) among women exposed to human papillomavirus (HPV) type 16, we performed a prospective study in a population-based cohort of more than 15,000 women followed for 34.9 months. Seventy-four women developed CIN during follow-up and were matched for age, time of sampling and area of residence with 148 women who remained CIN-free during follow-up. The blood samples taken at enrollment were tested for serum antibodies to HPV types 16, 18 and 33 capsids. Cervical smears or biopsies were analyzed for the presence of HPV DNA by nested PCR using HPV general primers and by HPV 16- and 18-type-specific PCR. HPV serology and HPV-…
A membrane-destabilizing peptide in capsid protein L2 is required for egress of papillomavirus genomes from endosomes
ABSTRACT Papillomaviruses are internalized via clathrin-dependent endocytosis. However, the mechanism by which viral genomes pass endosomal membranes has not been elucidated. In this report we show that the minor capsid protein L2 is required for egress of viral genomes from endosomes but not for initial uptake and uncoating and that a 23-amino-acid peptide at the C terminus of L2 is necessary for this function. Pseudogenomes encapsidated by L1 and L2 lacking this peptide accumulated in vesicular compartments similar to that observed with L1-only viral particles, and these mutant pseudoviruses were noninfectious. This L2 peptide displayed strong membrane-disrupting activity, induced cytolys…
Serological evidence for protection by human papillomavirus (HPV) type 6 infection against HPV type 16 cervical carcinogenesis
Human papillomavirus (HPV) exists as more than 100 genotypes. It is not well-established whether the different HPV types interfere with infection or pathogenesis by each other. Possible interactions in cervical carcinogenesis between infection with the most common HPV types (6, 11, 16, 18 and 33) were studied in a seroepidemiological case- control study of 218 women with primary untreated cervical cancer and 219 healthy age-matched control women. As previously shown, HPV-16 seropositivity was associated with cervical cancer risk [odds ratio (OR), 2·39], but HPV-16 was not associated with cervical cancer risk among HPV-6 seropositive women (OR, 1·0). The relative excess risk due to interacti…
Sero-epidemiologal association between human-papillomavirus infection and risk of prostate cancer
Some epidemiological studies of prostate cancer have suggested the existence of a sexually transmitted risk factor, and some studies have reported the presence of human papillomavirus (HPV) DNA in prostate-cancer tissue. To perform a sero-epidemiological evaluation of whether HPV infection is associated with increased risk for prostate cancer, we performed a nested case-control study within a serum bank containing samples from 20,243 healthy Finnish men. We identified 165 cases of prostate cancer that were diagnosed up to 24 years after donation of the serum sample. Two control subjects per case were selected, matched for gender, age and municipality of residence. Serum samples were analyze…
A survey of seroprevalence of human papillomavirus types 16, 18 and 33 among children.
The importance and natural history of HPV infections in childhood is incompletely understood. We performed a survey for presence of serum antibodies to HPV capsids among 1031 children aged 0 to 13 years, resident in Stockholm, Sweden. The HPV seroprevalence among these children was 3.0% for HPV16, 0.6% for HPV18 and 2.7% for HPV33. By comparison, among simultaneously analyzed positive control panels comprising women with CIN or healthy women with type-specific cervical HPV DNA, seroprevalence of HPV 16, 18 and 33 was 69%, 58% and 63% respectively. The results suggest that HPV infection in childhood is not common.