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RESEARCH ARTICLE
Contents Vol 10(1)

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

Sarah E. Tan A B G , Suzanne M. Garland A B C , Alice R. Rumbold D E , Ibrahim Zardawi F , Debbie Taylor-Thomson E , John R. Condon E and Sepehr N. Tabrizi A B C
+ Author Affiliations
- Author Affiliations

A Clinical Microbiology and Infectious Diseases, Royal Women’s Hospital, and Department of Obstetrics and Gynaecology, University of Melbourne, Royal Women’s Hospital, Cnr Flemington Road and Grattan Street, Parkville, Vic. 3052, Australia.

B World Health Organisation Human Papillomavirus LabNet Regional Reference Laboratory – Western Pacific Region, Melbourne, Vic. 3052, Australia.

C Infectious Diseases and Microbiology Group, Murdoch Children’s Research Institute, Bio 21 Institute, Level 1, Building 404, 30 Flemington Road, Parkville, Vic. 3052, Australia.

D Discipline of Obstetrics & Gynaecology, The University of Adelaide, Adelaide, SA 5005, Australia.

E Epidemiology and Health Systems Division, Menzies School of Health Research, PO Box 41096, Casuarina, NT 0811, Australia.

F Discipline of Anatomical Pathology, University of Newcastle, Manning Health Campus, PO Box 649, Taree, NSW 2430, Australia.

G Corresponding author. Email: s.tan39@student.unimelb.edu.au

Sexual Health 10(1) 18-25 https://doi.org/10.1071/SH11179
Submitted: 12 December 2011  Accepted: 21 May 2012   Published: 19 November 2012

Abstract

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.

Additional keywords: Aboriginal, Australia, high-risk human papillomavirus, Indigenous, vulvar intraepithelial neoplasia.


References

[1]  Sankaranarayanan R, Ferlay J. Worldwide burden of gynaecological cancer: the size of the problem. Best Pract Res Clin Obstet Gynaecol 2006; 20 207–25.
| Worldwide burden of gynaecological cancer: the size of the problem.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BD287ltlSrtQ%3D%3D&md5=fccebd73675fc338408d0bc522da0b97CAS | 16359925PubMed |

[2]  Crum CP. Carcinoma of the vulva: epidemiology and pathogenesis. Obstet Gynecol 1992; 79 448–54.
| Carcinoma of the vulva: epidemiology and pathogenesis.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaK387kvF2luw%3D%3D&md5=4b74c8ecec62627cebc804c5941d4b17CAS | 1310806PubMed |

[3]  Scurry JP, Vanin K. Vulvar squamous cell carcinoma and lichen sclerosus. Australas J Dermatol 1997; 38 S20–5.
| 10994466PubMed |

[4]  Smith JS, Backes DM, Hoots BE, Kurman RJ, Pimenta JM. Human papillomavirus type-distribution in vulvar and vaginal cancers and their associated precursors. Obstet Gynecol 2009; 113 917–24.
| 19305339PubMed |

[5]  Sideri M, Jones RW, Wilkinson EJ, Preti M, Heller DS, Scurry J, et al Squamous vulvar intraepithelial neoplasia: 2004 modified terminology, ISSVD Vulvar Oncology Subcommittee. J Reprod Med 2005; 50 807–10.
| 16419625PubMed |

[6]  De Vuyst H, Clifford GM, Nascimento MC, Madeleine MM, Franceschi S. Prevalence and type distribution of human papillomavirus in carcinoma and intraepithelial neoplasia of the vulva, vagina and anus: a meta-analysis. Int J Cancer 2009; 124 1626–36.
| Prevalence and type distribution of human papillomavirus in carcinoma and intraepithelial neoplasia of the vulva, vagina and anus: a meta-analysis.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXivVars74%3D&md5=1ac1525531c054ca2c735a8bc85056aaCAS | 19115209PubMed |

[7]  Sichero L, Ferreira S, Trottier H, Duarte-Franco E, Ferenczy A, Franco EL, et al High grade cervical lesions are caused preferentially by non-European variants of HPVs 16 and 18. Int J Cancer 2007; 120 1763–8.
| High grade cervical lesions are caused preferentially by non-European variants of HPVs 16 and 18.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXjtFOktb8%3D&md5=52821f9293f56b502f86b5f03ae4e937CAS | 17230525PubMed |

[8]  Picconi MA, Alonio LV, Sichero L, Mbayed V, Villa LL, Gronda J, et al Human papillomavirus type-16 variants in Quechua aboriginals from Argentina. J Med Virol 2003; 69 546–52.
| Human papillomavirus type-16 variants in Quechua aboriginals from Argentina.Crossref | GoogleScholarGoogle Scholar | 12601763PubMed |

[9]  de Koning MN, Quint WG, Pirog EC. Prevalence of mucosal and cutaneous human papillomaviruses in different histologic subtypes of vulvar carcinoma. Mod Pathol 2008; 21 334–44.
| Prevalence of mucosal and cutaneous human papillomaviruses in different histologic subtypes of vulvar carcinoma.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXisVKmtb8%3D&md5=54aceaa560ed385fe3960d1f027ceebbCAS | 18192968PubMed |

[10]  Jones RW, Baranyai J, Stables S. Trends in squamous cell carcinoma of the vulva: the influence of vulvar intraepithelial neoplasia. Obstet Gynecol 1997; 90 448–52.
| Trends in squamous cell carcinoma of the vulva: the influence of vulvar intraepithelial neoplasia.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaK2svitlOiug%3D%3D&md5=0ab7b83f2ee34292da9695627321e6a5CAS | 9277660PubMed |

[11]  Iversen T, Tretli S. Intraepithelial and invasive squamous cell neoplasia of the vulva: trends in incidence, recurrence, and survival rate in Norway. Obstet Gynecol 1998; 91 969–72.
| Intraepithelial and invasive squamous cell neoplasia of the vulva: trends in incidence, recurrence, and survival rate in Norway.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaK1c3nt1GlsA%3D%3D&md5=e6b4041787014013cf24bf33c961d3a1CAS | 9611006PubMed |

[12]  Joura EA. Epidemiology, diagnosis and treatment of vulvar intraepithelial neoplasia. Curr Opin Obstet Gynecol 2002; 14 39–43.
| Epidemiology, diagnosis and treatment of vulvar intraepithelial neoplasia.Crossref | GoogleScholarGoogle Scholar | 11801875PubMed |

[13]  Condon JR, Rumbold AR, Thorn JC, O’Brien MM, Davy MJ, Zardawi I. A cluster of vulvar cancer and vulvar intraepithelial neoplasia in young Australian indigenous women. Cancer Causes Control 2009; 20 67–74.
| A cluster of vulvar cancer and vulvar intraepithelial neoplasia in young Australian indigenous women.Crossref | GoogleScholarGoogle Scholar | 18766449PubMed |

[14]  Foley MZY, Condon J. Demographic data quality assessment for Northern Territory public hospitals 2011. Darwin: Department of Health; 2012.

[15]  Garland SM, Hernandez-Avila M, Wheeler CM, Perez G, Harper DM, Leodolter S, et al Quadrivalent vaccine against human papillomavirus to prevent anogenital diseases. N Engl J Med 2007; 356 1928–43.
| Quadrivalent vaccine against human papillomavirus to prevent anogenital diseases.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXltFSmtLo%3D&md5=1c0215257874491c9d2fd9b24fdc436dCAS | 17494926PubMed |

[16]  van Hamont D, van Ham MA, Bakkers JM, Massuger LF, Melchers WJ. Evaluation of the SPF10-INNO LiPA human papillomavirus (HPV) genotyping test and the roche linear array HPV genotyping test. J Clin Microbiol 2006; 44 3122–9.
| Evaluation of the SPF10-INNO LiPA human papillomavirus (HPV) genotyping test and the roche linear array HPV genotyping test.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28XhtVGnt7%2FE&md5=7ae27154637700b1b4b206b229c6b74bCAS | 16954236PubMed |

[17]  Schiffman M, Clifford G, Buonaguro FM. Classification of weakly carcinogenic human papillomavirus types: addressing the limits of epidemiology at the borderline. Infect Agent Cancer 2009; 4 8–16.
| Classification of weakly carcinogenic human papillomavirus types: addressing the limits of epidemiology at the borderline.Crossref | GoogleScholarGoogle Scholar | 19486508PubMed |

[18]  Muñoz N, Bosch FX, de Sanjose S, Herrero R, Castellsague X, Shah KV, et al Epidemiologic classification of human papillomavirus types associated with cervical cancer. N Engl J Med 2003; 348 518–27.
| Epidemiologic classification of human papillomavirus types associated with cervical cancer.Crossref | GoogleScholarGoogle Scholar | 12571259PubMed |

[19]  Klaes R, Friedrich T, Spitkovsky D, Ridder R, Rudy W, Petry U, et al Overexpression of p16INK4A as a specific marker for dysplastic and neoplastic epithelial cells of the cervix uteri. Int J Cancer 2001; 92 276–84.
| Overexpression of p16INK4A as a specific marker for dysplastic and neoplastic epithelial cells of the cervix uteri.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3MXivVKqurw%3D&md5=ba4860427100d5e08c91fc6e373edbdaCAS | 11291057PubMed |

[20]  Skapa P, Zamecnik J, Hamsikova E, Salakova M, Smahelova J, Jandova K, et al Human papillomavirus (HPV) profiles of vulvar lesions: possible implications for the classification of vulvar squamous cell carcinoma precursors and for the efficacy of prophylactic HPV vaccination. Am J Surg Pathol 2007; 31 1834–43.
| Human papillomavirus (HPV) profiles of vulvar lesions: possible implications for the classification of vulvar squamous cell carcinoma precursors and for the efficacy of prophylactic HPV vaccination.Crossref | GoogleScholarGoogle Scholar | 18043037PubMed |

[21]  Srodon M, Stoler MH, Baber GB, Kurman RJ. The distribution of low and high-risk HPV types in vulvar and vaginal intraepithelial neoplasia (VIN and VaIN). Am J Surg Pathol 2006; 30 1513–8.
| The distribution of low and high-risk HPV types in vulvar and vaginal intraepithelial neoplasia (VIN and VaIN).Crossref | GoogleScholarGoogle Scholar | 17122506PubMed |

[22]  van Beurden M, ten Kate FJ, Smits HL, Berkhout RJ, de Craen AJ, van der Vange N, et al Multifocal vulvar intraepithelial neoplasia grade III and multicentric lower genital tract neoplasia is associated with transcriptionally active human papillomavirus. Cancer 1995; 75 2879–84.
| Multifocal vulvar intraepithelial neoplasia grade III and multicentric lower genital tract neoplasia is associated with transcriptionally active human papillomavirus.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaK2M3pt1alsw%3D%3D&md5=7dd60ea80152fa5ec80ffb9216e26e7dCAS | 7773937PubMed |

[23]  Tornesello ML, Duraturo ML, Salatiello I, Buonaguro L, Losito S, Botti G, et al Analysis of human papillomavirus type-16 variants in Italian women with cervical intraepithelial neoplasia and cervical cancer. J Med Virol 2004; 74 117–26.
| Analysis of human papillomavirus type-16 variants in Italian women with cervical intraepithelial neoplasia and cervical cancer.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2cXntFGltb8%3D&md5=3f32e3bd91462d9f241c0954d001017dCAS | 15258977PubMed |

[24]  Rufforny I, Wilkinson EJ, Liu C, Zhu H, Buteral M, Massoll NA. Human papillomavirus infection and p16INK4a protein expression in vulvar intraepithelial neoplasia and invasive squamous cell carcinoma. J Low Genit Tract Dis 2005; 9 108–13.
| Human papillomavirus infection and p16INK4a protein expression in vulvar intraepithelial neoplasia and invasive squamous cell carcinoma.Crossref | GoogleScholarGoogle Scholar | 15870532PubMed |

[25]  Tringler B, Grimm C, Dudek G, Zeillinger R, Tempfer C, Speiser P, et al p16INK4a expression in invasive vulvar squamous cell carcinoma. Appl Immunohistochem Mol Morphol 2007; 15 279–83.
| p16INK4a expression in invasive vulvar squamous cell carcinoma.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXhtFGqu7bK&md5=e2b535096178a67d45e906b4010e4403CAS | 17721272PubMed |

[26]  Riethdorf S, Neffen EF, Cviko A, Loning T, Crum CP, Riethdorf L. p16INK4A expression as biomarker for HPV 16-related vulvar neoplasias. Hum Pathol 2004; 35 1477–83.
| p16INK4A expression as biomarker for HPV 16-related vulvar neoplasias.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2cXhtVyku77N&md5=23f88df6d4bc5150b4ff31188bcec884CAS | 15619206PubMed |

[27]  Ferrer I, Armstrong J, Capellari S, Parchi P, Arzberger T, Bell J, et al Effects of formalin fixation, paraffin embedding, and time of storage on DNA preservation in brain tissue: a BrainNet Europe study. Brain Pathol 2007; 17 297–303.
| Effects of formalin fixation, paraffin embedding, and time of storage on DNA preservation in brain tissue: a BrainNet Europe study.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXptFOlurg%3D&md5=d796f548f1314903c63786b9bdf259faCAS | 17465988PubMed |

[28]  Hussain SK, Madeleine MM, Johnson LG, Du Q, Malkki M, Wilkerson HW, et al Cervical and vulvar cancer risk in relation to the joint effects of cigarette smoking and genetic variation in interleukin 2. Cancer Epidemiol Biomarkers Prev 2008; 17 1790–9.
| Cervical and vulvar cancer risk in relation to the joint effects of cigarette smoking and genetic variation in interleukin 2.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXosFGhtrs%3D&md5=278507cc280124588ee942c775de6992CAS | 18628433PubMed |

[29]  Jamieson DJ, Paramsothy P, Cu-Uvin S, Duerr A. Vulvar, vaginal, and perianal intraepithelial neoplasia in women with or at risk for human immunodeficiency virus. Obstet Gynecol 2006; 107 1023–8.
| Vulvar, vaginal, and perianal intraepithelial neoplasia in women with or at risk for human immunodeficiency virus.Crossref | GoogleScholarGoogle Scholar | 16648406PubMed |

[30]  Cunningham J. Occasional paper: cigarette smoking among Indigenous Australians. Canberra: Australian Bureau of Statistics; 1997.

[31]  National Centre in HIV Epidemiology and Clinical Research (NCHECR) Bloodborne viral and sexually transmitted infections in Aboriginal and Torres Strait Islander people: surveillance and evaluation report.. Sydney: NCHECR; 2010.

[32]  Davidson EJ, Davidson JA, Sterling JC, Baldwin PJ, Kitchener HC, Stern PL. Association between human leukocyte antigen polymorphism and human papillomavirus 16-positive vulval intraepithelial neoplasia in British women. Cancer Res 2003; 63 400–3.
| 1:CAS:528:DC%2BD3sXnt1Krtw%3D%3D&md5=cfebc97090f7977a66b3675dfcd2efb1CAS | 12543794PubMed |