Investigating a cluster of vulvar cancers in young women: distribution of human papillomavirus and HPV-16 variants in vulvar dysplastic or neoplastic biopsies

Sexual Health ◽  
2013 ◽  
Vol 10 (1) ◽  
pp. 18 ◽  
Author(s):  
Sarah E. Tan ◽  
Suzanne M. Garland ◽  
Alice R. Rumbold ◽  
Ibrahim Zardawi ◽  
Debbie Taylor-Thomson ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
Vulvar Cancer ◽  
Intraepithelial Neoplasia ◽  
Indigenous Women ◽  
Invasive Cancer ◽  
Vulvar Intraepithelial Neoplasia ◽  
High Grade ◽  
Hpv 16 ◽  
Significant Difference ◽  
Arnhem Land

Background A high incidence of vulvar cancer, and its precursor lesion, high-grade vulvar intraepithelial neoplasia (VIN) has been identified in young Indigenous women living in the Arnhem Land region of the Northern Territory (NT) of Australia. This clustering is restricted to women aged <50 years, suggesting that oncogenic human papillomavirus (HPV) is a key causal factor. This study compared the HPV genotype prevalence, HPV-16 variant distribution and p16INK4aexpression in stored vulvar cancer and high-grade VIN biopsy specimens from women residing in Arnhem Land, with specimens taken from Indigenous and non-Indigenous women in other regions of NT where there is no observed increase in vulvar cancer incidence. Methods: Twenty high-grade VIN and 10 invasive cancer biopsies were assessed from Arnhem Land along with 24 high-grade VIN and 10 invasive cancer biopsies from other regions of NT. Results: Biopsies from Arnhem Land were similar to those from other regions in the detection of high-risk (HR) or possible HR HPV (VIN: 95% and 84% respectively for Arnhem Land and other regions, P = 0.356; invasive cancer: 100% and 80%, P = 0.473), HPV-16 (VIN: 60% and 80%, P = 0.364; invasive cancer: 70% and 70%, P = 1.0) and p16INK4a expression (VIN: 90% and 84%, P = 0.673; invasive cancer: 100% and 80%, P = 0.474). All HPV-16 variants were of the European prototype. Conclusion: Comparison of biopsies revealed no significant difference in the frequency of oncogenic HPVs or HPV-16 variant types between Arnhem Land and other regions, suggesting another cofactor in this cluster.

Serologic response to human papillomavirus 16 among Australian women with high-grade cervical intraepithelial neoplasia

2006 ◽  
Vol 16 (3) ◽  
pp. 1032-1035
Author(s):  
S. N. Tabrizi ◽  
I. H. Frazer ◽  
S. M. Garland
Keyword(s):  
Human Papillomavirus ◽  
Cervical Intraepithelial Neoplasia ◽  
Intraepithelial Neoplasia ◽  
High Grade ◽  
Hpv 16 ◽  
Hpv Dna ◽  
Human Papillomavirus 16 ◽  
Serologic Response ◽  
Poor Predictor ◽  
Hpv Types

This study evaluated the detection of human papillomavirus (HPV) 16 antibody in HPV 16–associated cervical intraepithelial neoplasia (CIN) in Australian women. Seroreactivity to HPV 16 L1 virus–like particles was assessed in patients with CIN 2 (n = 169) and CIN 3 (n = 229) lesions previously tested for the presence of HPV DNA. Seropositivity was significantly commoner in women with HPV 16 DNA–positive lesions (98/184) than in women with no HPV DNA in the lesion (15/47) or with HPV of types other than 16 in the lesion (43/167) (P = 0.0004). In addition, seropositivity was observed in 33% (55/169) of women with CIN 2 and 46% (106/229) of women with CIN 3, in keeping with the lower fraction of CIN 2 (57/169) than CIN 3 (127/229) biopsies positive for HPV 16 DNA. HPV 16 seropositivity is most common in women with HPV 16–associated CIN, but many patients with HPV-associated CIN 3 are seronegative, and HPV 16 seropositivity is common in women with CIN associated with other HPV types. Overall, HPV 16 serology is a poor predictor of presence of HPV 16–associated CIN 3 in patient population studied.

Human papillomavirus (HPV) type 16-specific CD8+ T cell responses in women with high grade vulvar intraepithelial neoplasia

2004 ◽  
Vol 108 (6) ◽  
pp. 857-862 ◽  
Author(s):  
Richard W. Todd ◽  
Sally Roberts ◽  
Christopher H. Mann ◽  
David M. Luesley ◽  
Phillip H. Gallimore ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
T Cell ◽  
T Cell Responses ◽  
Intraepithelial Neoplasia ◽  
Cd8 T Cell ◽  
Vulvar Intraepithelial Neoplasia ◽  
High Grade ◽  
Cell Responses

scholarly journals Seroepidemiology of Human Papillomavirus 16 (HPV16) L2 and Generation of L2-Specific Human Chimeric Monoclonal Antibodies

2015 ◽  
Vol 22 (7) ◽  
pp. 806-816 ◽  
Author(s):  
Joshua W. Wang ◽  
Subhashini Jagu ◽  
Wai-Hong Wu ◽  
Raphael P. Viscidi ◽  
Anne Macgregor-Das ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Human Papillomavirus ◽  
Neutralizing Antibodies ◽  
Intraepithelial Neoplasia ◽  
Vulvar Intraepithelial Neoplasia ◽  
Enzyme Linked Immunosorbent Assay ◽  
High Grade ◽  
Phase Ii Trials ◽  
Serum Samples ◽  
Hpv Dna

ABSTRACTPresently, the seroprevalence of human papillomavirus (HPV) minor capsid antigen L2-reactive antibody is not well understood, and no serologic standard exists for L2-specific neutralizing antibodies. Therefore, we screened a total of 1,078 serum samples for HPV16 L2 reactivity, and these were obtained from four prior clinical studies: a population-based (n= 880) surveillance study with a high-risk HPV DNA prevalence of 10.8%, a cohort study of women (n= 160) with high-grade cervical intraepithelial neoplasia (CIN), and two phase II trials in women with high-grade vulvar intraepithelial neoplasia (VIN) receiving imiquimod therapy combined with either photodynamic therapy (PDT) (n= 19) or vaccination with a fusion protein comprising HPV16 L2, E7, and E6 (TA-CIN) (n= 19). Sera were screened sequentially by HPV16 L2 enzyme-linked immunosorbent assay (ELISA) and then Western blot. Seven of the 1,078 serum samples tested had L2-specific antibodies, but none were detectably neutralizing for HPV16. To develop a standard, we substituted human IgG1 sequences into conserved regions of two rodent monoclonal antibodies (MAbs) specific for neutralizing epitopes at HPV16 L2 residues 17 to 36 and 58 to 64, creating JWW-1 and JWW-2, respectively. These chimeric MAbs retained neutralizing activity and together reacted with 33/34 clinically relevant HPV types tested. In conclusion, our inability to identify an HPV16 L2-specific neutralizing antibody response even in the sera of patients with active genital HPV disease suggests the subdominance of L2 protective epitopes and the value of the chimeric MAbs JWW-1 and JWW-2 as standards for immunoassays to measure L2-specific human antibodies.

scholarly journals Phylogenetic classification of human papillomavirus genotypes in high-grade cervical intraepithelial neoplasia in women from a densely populated Brazilian urban region

2009 ◽  
Vol 127 (3) ◽  
pp. 122-127 ◽  
Author(s):  
Denise Rocha Pitta ◽  
Luis Otávio Sarian ◽  
Elisabete Aparecida Campos ◽  
Sílvia Helena Rabelo-Santos ◽  
Kari Syrjänen ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
Cervical Intraepithelial Neoplasia ◽  
Intraepithelial Neoplasia ◽  
Multiple Infections ◽  
High Grade ◽  
Hpv 16 ◽  
Phylogenetic Classification ◽  
Hpv Genotypes ◽  
Hpv Types ◽  
Hpv 18

CONTEXT AND OBJECTIVE: Differences in human papillomavirus (HPV) types may correlate with the biological potential and invasion risk of high-grade cervical intraepithelial neoplasia (CIN 2 and CIN 3). The objective of this study was to determine the relationship between different combinations of HPV types and CIN severity. DESIGN AND SETTING: Cross-sectional study, at Universidade Estadual de Campinas (Unicamp). METHODS: Cervical samples from 106 women treated due to CIN 2 (18) or CIN 3 (88) were examined for specific HPV genotypes using Roche Linear Array® (LA-HPV). The proportions of CIN 2 and CIN 3 in groups of women infected with the HPV phylogenetic groups A7 and A9 were compared. Three groups were formed: women with single infections; multiple infections; and the whole sample. RESULTS: Multiple infections were detected in 68 samples (64.7%). The most frequent high-risk genotypes detected (single/multiple) were HPV 16 (57.1%), HPV 58 (24.7%), HPV 33 (15.2%), HPV 52 (13.3%), HPV 31 (10.4%), HPV 51 (7.6%) and HPV 18 (6.6%). Women without infection with HPV species Alpha 9 were less likely to have CIN 3 than were their Alpha 9 HPV-infected counterparts. HPV 16 and/or HPV 18, with or without associations with other viral types, were more frequently found in women with CIN 3 than in those with CIN 2. CONCLUSIONS: The severity of high-grade CIN may be aggravated by the presence of HPV types included in the Alpha 9 phylogenetic classification and by infections including HPV 16 and 18, singly or in combination with other HPV genotypes.

Low-level amplifications of the human telomerase gene (TERC) regularly is associated with vulvar intraepithelial neoplasia

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 20060-20060
Author(s):  
G. Gebauer ◽  
J. Schleibaum ◽  
S. Aulmann ◽  
P. Schirmacher ◽  
C. Sohn ◽  
...  
Keyword(s):  
Copy Number ◽  
Gene Locus ◽  
Vulvar Cancer ◽  
Intraepithelial Neoplasia ◽  
Vulvar Intraepithelial Neoplasia ◽  
Gene Copy ◽  
Chromosome 3 ◽  
High Grade ◽  
Two Samples ◽  
Human Telomerase

20060 Background: Invasive squamous carcinomas of the vulva frequently harbor gains on the long arm of chromosome 3, including the human telomerase gene locus (TERC). Vulvar cancer develops from precursor lesions known as vulvar intraepithelial neoplasia (VIN) which frequently occur simultaneously in multiple locations and have a considerable risk or recurrence during follow-up. We investigated TERC gene copy number in a series of vulvar intraepithelial neoplasias to determine the risk of progression in these lesions. Methods: A total of 20 cases of high grade vulvar intraepithelial neoplasias (VIN 3) were analyzed using a two-color fluorescence in situ hybridization (FISH) assay detecting the human telomerase gene locus (3q26) on paraffin embedded tissue sections. Two samples were excluded for technical reasons. Results: In 11 cases, gains of chromosomal material at 3q26 were detected with an average of 1.48 copies per chromosome. In another patient a high level amplification was found. The remaining two cases, four centromere and 3q26 hybridization signals were observed, consistent with a tetraploidy of chromosome 3. No changes in DNA copy number on chromosome 3q were detected only in four lesions. Conclusions: Our findings demonstrate high frequency of gains on chromosome 3q in the majority of high grade vulvar lesions. This suggests an involvement of the human telomerase gene locus in the pathogenesis of vulvar cancer. No significant financial relationships to disclose.

A cluster of vulvar cancer and vulvar intraepithelial neoplasia in young Australian Indigenous women

2008 ◽  
Vol 20 (1) ◽  
pp. 67-74 ◽  
Author(s):  
John R. Condon ◽  
Alice R. Rumbold ◽  
Jane C. Thorn ◽  
Margaret M. O’Brien ◽  
Margaret J. Davy ◽  
...  
Keyword(s):  
Vulvar Cancer ◽  
Intraepithelial Neoplasia ◽  
Indigenous Women ◽  
Vulvar Intraepithelial Neoplasia
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