Investigating a cluster of vulvar cancer in young women: a cross-sectional study of genital human papillomavirus prevalence

BMC Infectious Diseases

Suzanne M Garland¹  Jim Stankovich⁸  Ibrahim Zardawi³  Christine M Connors¹  Margaret M O’Brien⁵  Margaret LJ Davy⁶  Sepehr N Tabrizi¹  Maria Nickels²  Debbie Taylor-Thomson⁴  John R Condon⁴  Sarah E Tan⁷  Alice R Rumbold⁴ 

[1] Infectious Diseases and Microbiology Group, Murdoch Children’s Research Institute, Bio 21 Institute, Level 1 Building 404, 30 Flemington Rd, Parkville, Victoria 3052, Australia;Health Services Division, Northern Territory Department of Health, PO Box 40596, Casuarina, NT 0811, Australia;Discipline of Anatomical Pathology, University of Newcastle, Manning Health Campus, PO Box 649, Taree, NSW, 2430, Australia;Epidemiology and Health Systems Division, Menzies School of Health Research, PO Box 41096, Casuarina, NT 0811, Australia;Department of Obstetrics and Gynaecology, Cairns Base Hospital, The Esplanade, Cairns, QLD 4870, Australia;Surgical and Specialties Service, Royal Adelaide Hospital, North Tce, Adelaide, SA 5000, Australia;WHO HPV LabNet Regional Reference Laboratory - Western Pacific Region, Melbourne, VIC, Australia;Biostatistics Group, Menzies Research Institute Tasmania, University of Tasmania, Medical Sciences Building 1, 17 Liverpool Street, Private Bag 23, Hobart, TAS 7000, Australia

关键词: Indigenous women;    Young women;    Vulvar neoplasms;    Population prevalence;    Human papillomavirus;   

Others  :  1159648
DOI  :  10.1186/1471-2334-12-243

 received in 2011-11-11, accepted in 2012-09-27,  发布年份 2012

【 摘 要 】

Background

Vulvar cancer is a relatively rare malignancy, which occurs most often in postmenopausal women. We have previously identified a geographic cluster of vulvar cancer in young Indigenous women living in remote communities in the Arnhem Land region of Australia. In this population, we investigated the prevalence of oncogenic human papillomavirus (HPV) infection in anogenital samples (vulvar/vaginal/perianal area and cervix) and compared the overall, type-specific and multiple infection prevalence between sites.

Methods

A cross-sectional survey of 551 Indigenous women aged 18–60 years was undertaken in 9 Arnhem Land communities. Women were consented for HPV detection and genotyping collected by a combined vulvar/vaginal/perianal (VVP) sweep swab and a separate PreservCyt endocervical sample collected during Pap cytology screening. HPV DNA testing was undertaken using PCR with broad spectrum L1 consensus PGMY09/11 primers with genotyping of positive samples by Roche Linear Array. The primary outcomes were the prevalence of cervical and VVP high-risk (HR) HPV.

Results

The prevalence of VVP HR-HPV was 39%, which was significantly higher than the cervical HR-HPV prevalence (26%, p<0.0001). HPV-16 was the most common genotype detected in both sites (VVP 11%, cervical 6%). HPV-16 infection peaked in women aged <20 years; however, there was a marked decline in cervical HPV-16 prevalence with age (p=0.007), whereas following an initial decline, the prevalence of VVP HPV-16 remained constant in subsequent age-groups (p=0.835).

Conclusions

In this population experiencing a cluster of vulvar cancer, the prevalence of cervical oncogenic HPV infection was similar to that reported by studies of other Australian women; however there was a significantly higher prevalence of vulvar/vaginal/perianal infection to cervical. The large discrepancy in HPV prevalence between anogenital sites in this population may represent more persistent infection at the vulva. This needs further investigation, including the presence of possible environmental and/or genetic factors that may impair host immunity.

【 授权许可】

   
2012 Rumbold et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

【 参考文献 】

• [1]Sankaranarayanan R, Ferlay J: Worldwide burden of gynaecological cancer: The size of the problem. Best Pract Res Clin Obstet Gynaecol 2006, 20(2):207-225.
• [2]van Beurden M, ten Kate FJ, Smits HL, Berkhout RJ, de Craen AJ, van der Vange N, Lammes FB, ter Schegget J: Multifocal vulvar intraepithelial neoplasia grade III and multicentric lower genital tract neoplasia is associated with transcriptionally active human papillomavirus. Cancer 1995, 75(12):2879-2884.
• [3]Scurry JP, Vanin K: Vulvar squamous cell carcinoma and lichen sclerosus. Australas J Dermatol 1997, 38(Suppl 1):S20-S25.
• [4]Curado MP, Edwards B, Shin HR, Storm H, Ferlay J, Heanue M, Boyle P: Cancer Incidence in Five Continents, Vol. IX. Lyon, France: IARC; 2007.
• [5]Sturgeon SR, Brinton LA, Devessa SS, Kurman RJ: In situ and invasive vulvar cancer incidence trends (1973–1987). Am J Obstet Gynecol 1992, 166(5):1482-1485.
• [6]Jones RW, Ranayai JU, Stables S: Trends in squamous cell carcinoma of the vulva: the influence of vulvar intraepithelial neoplasia. Obstet Gynecol 1997, 90(3):448-452.
• [7]Iversen T, Tretli SI: Intraepithelial and invasive squamous cell neoplasia of the vulva: Trends in incidence, recurrence and survival rate in Norway. Obstet Gynecol 1998, 91:969-972.
• [8]Condon JR, Rumbold AR, Thorn JC, O’Brien MM, Davy M, Zardawi I: A cluster of vulvar cancer and vulvar intraepithelial neoplasia in young Australian Indigenous women. Cancer Causes Control 2009, 20(1):67-74.
• [9]Garland S, Hernandez-Avila M, Wheeler CM, Perez G, Harper DM, Leodolter S, Tang GWK, Ferris DG, Steben M, Bryan J, et al.: Quadrivalent Vaccine against Human Papillomavirus to Prevent Anogenital Diseases. N Engl J Med 2007, 356:1928-1943.
• [10]Stevens MP, Rudland E, Garland SM, Tabrizi SN: Assessment of MagNA pure LC extraction system for detection of human papillomavirus (HPV) DNA in PreservCyt samples by the Roche AMPLICOR and LINEAR ARRAY HPV tests. J Clin Microbiol 2006, 44(7):2428-2433.
• [11]Manos MM, Ting Y, Wright DK, Lewis AJ, Broker TR, Wolinsky SM: The use of polymerase chain reaction amplification for the detection of genital human papillomaviruses. Cancer Cells 1989, 7:209-214.
• [12]Resnick RM, Cornelissen MT, Wright DK, Eichinger GH, Fox HS, ter Schegget J, Manos MM: Detection and typing of human papillomavirus in archival cervical cancer specimens by DNA amplification with consensus primers. J Natl Cancer Inst 1990, 82:1477-1484.
• [13]Bauer HM, Ting Y, Greer CE, Chambers JC, Tashiro CJ, Chimera J, Reingold A, Manos MM: Genital human papillomavirus infection in female university students as determined by a PCR-based method. JAMA 1991, 265:472-477.
• [14]Layton-Henry J, Scurry JS, Planner RS, Allen D, Sykes P, Garland SM, Borg AJ, Tabrizi SN: Cervical adenoid basal carcinoma, five cases and literature review. Int J Gynecol Cancer 1996, 6(3):193-199.
• [15]Stevens MP, Garland SM, Tabrizi SN: Human papillomavirus genotyping using a modified linear array detection protocol. J Virol Methods 2006, 135(1):124-126.
• [16]Tabrizi SN, Stevens M, Chen S, Rudland E, Kornegay JR, Garland SM: Evaluation of a modified reverse line blot assay for detection and typing of human papillomavirus. Am J Clin Pathol 2005, 123(6):896-899.
• [17]Stevens MP, Garland SM, Tabrizi SN: Development and validation of a real-time PCR assay specifically detecting human papillomavirus 52 using the Roche LightCycler 480 system. J Virol Methods 2008, 147(2):290-296.
• [18]Schiffman M, Clifford G, Buonaguro L: Classification of weakly carcinogenic human papillomavirus types: addressing the limits of epidemiology at the borderline. Infect Agent Cancer 2009, 4:8. BioMed Central Full Text
• [19]Garland SM, Brotherton JML, Condon JR, McIntyre PB, Stevens MP, Smith DW, Tabrizi SN, on behalf of the WHINURS study group: Human papillomavirus prevalence amongst Indigenous and non-Indigenous Australian women prior to a national HPV vaccination program. BMC Med 2011, 9:104. BioMed Central Full Text
• [20]Winer RL, Feng Q, Hughes JP, Yu M, Kiviat NB, O'Reilly S, Koutsky LA: Concordance of self-collected and clinician-collected swab samples for detecting human papillomavirus DNA in women 18 to 32 years of age. Sex Transm Dis 2007, 34(6):371-377.
• [21]Brown DR, Shew ML, Qadadri B, Neptune N, Vargas M, Tu W, Juliar BE, Breen TE, Fortenberry JD: A longitudinal study of genital human papillomavirus infection in a cohort of closely followed adolescent women. J Infect Dis 2005, 191(2):182-192.
• [22]Canadas MP, Bosch FX, Junquera ML, Ejarque M, Font R, Ordonez E, de Sanjose S: Concordance of prevalence of human papillomavirus DNA in anogenital and oral infections in a high-risk population. J Clin Microbiol 2004, 42(3):1330-1332.
• [23]Goncalves MA, Randi G, Arslan A, Villa LL, Burattini MN, Franceschi S, Donadi EA, Massad E: HPV type infection in different anogenital sites among HIV-positive Brazilian women. Infect Agent Cancer 2008, 3:5. BioMed Central Full Text
• [24]Barzon L, Militello V, Pagni S, Franchin E, Dal Bello F, Mengoli C, Palu G: Distribution of human papillomavirus types in the anogenital tract of females and males. J Med Virol 2010, 82(8):1424-1430.
• [25]Jones C, Zhang X, Dempsey K, Schwarz N, Guthridge S: The Health and Wellbeing of Northern Territory Women: From the Desert to the Sea. Darwin: Department of Health and Community Services; 2005.
• [26]Kojic EM, Cu-Uvin S, Conley L, Bush T, Unger E, Henry K, Hammer J, Onen N, Palefsky J, Patel P: Human Papillomavirus (HPV) Infection of the Anus is More Diverse and Persistent than Cervical HPV infection among HIV infection in the SUN study. Abstract #1135. In 45th Annual Meeting of the Infectious Diseases Society of America (IDSA). San Diego, USA: IDSA; 2007.
• [27]Winer RL, Lee S, Hughes JP, Adam DE, Kiviat NB, Koutsky LA: Genital Human Papillomavirus Infection: Incidence and Risk Factors in a Cohort of Female University Students. Am J Epidemiol 2003, 157(3):218-226.
• [28]Winer RL, Hughes JP, Feng Q, O'Reilly S, Kiviat NB, Koutsky LA: Comparison of incident cervical and vulvar/vaginal human papillomavirus infections in newly sexually active young women. J Infect Dis 2009, 199(6):815-818.
• [29]Harper DM, Longacre MR, Noll WW, Belloni DR, Cole BF: Factors affecting the detection rate of human papillomavirus. Ann Fam Med 2003, 1(4):221-227.
• [30]Palefsky JM, Holly EA, Ralston MA, Da Costa M, Greenblatt RM: Prevalence and risk factors for anal human papillomavirus infection in human immunodeficiency virus (HIV)-positive and high-risk HIV-negative women. J Infect Dis 2001, 183(3):383-391.
• [31]Hussain SK, Madeleine MM, Johnson LG, Du Q, Malkki M, Wilkerson HW, Farin FM, Carter JJ, Galloway DA, Daling JR, 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(7):1790-1799.
• [32]Chondur R, Wang Z, Guthridge S: Smoking prevalence, Northern Territory. In Health Gains Planning Information Sheet. Northern Territory Department of Health; Available at: http://www.health.nt.gov.au/Health_Gains/Publications/index.aspx webcite (Accessed 8th March 2011); 2010