HPV Detection and Genotyping in Vulvar Squamous Cell Carcinoma in Northern Thailand

  • Published : 2014.04.30


Background: The study was aimed to evaluate the prevalence and genotype distribution of HPV infection in vulvar squamous cell carcinoma (SCC) in northern Thailand and the clinicopathological difference with regard to HPV infection status. Materials and Methods: Formalin-fixed paraffin-embedded tissue samples of vulvar SCC diagnosed between January 2006 and December 2012 were collected. HPV infection was detected by nested polymerase chain reaction (PCR) with primers MY09/11 and GP5+/6+. HPV genotyping was performed using the Linear Array Genotyping Test, followed by type-specific PCR targeting the E6/E7 region of HPV16/18/52 if the Linear Array test was negative. The histologic slides of vulvar lesions and the medical records were reviewed. Results: There were 47 cases of vulvar SCC included in the study (mean patient age $57.9{\pm}13.2$ years). HPV infection was detected in 29 cases (62%), all of which had single HPV infections. HPV16 accounted for 23 (49%). The patients with HPV-positive SCC had a significantly younger mean age than those with HPV-negative tumors (52.7 years vs 66.2 years, p<0.001). There was no significant difference in tumor stage distribution with regard to the status of HPV infection. The presence of vulvar intraepithelial neoplasia (VIN) of usual type (basaloid or warty) was significantly more frequent in HPV-positive cases compared with HPV-negative cases (62% vs 6%, p<0.001), whereas differentiated-type VIN was more common in HPV-negative cases (24% vs 0%, p=0.019). Conclusions: HPV infection was detected in 62% of vulvar SCC in northern Thailand. HPV16 was the predominant genotype similar to the data reported from other regions. HPV-positive SCC occurred in younger patients compared with HPV-negative SCC, and was associated with usual-type VIN. Vaccination against HPV16/18 may potentially prevent almost one half of vulvar SCC in northern Thailand.


  1. Alonso I, Fuste V, del Pino M, et al (2011). Does human papillomavirus infection imply a different prognosis in vulvar squamous cell carcinoma? Gynecol Oncol, 122, 509-14.
  2. Benedet JL, Bender H, Jones H, 3rd, et al (2000). FIGO staging classifications and clinical practice guidelines in the management of gynecologic cancers. FIGO Committee on Gynecologic Oncology. Int J Gynaecol Obstet, 70, 209-62.
  3. Curado MP, Edwards B, Shin HR, et al (2007). 'Cancer incidence in five continents', Vol. IX. Lyon: IARC Scientific Publications No.160.
  4. De Vuyst H, Clifford GM, Nascimento MC, et al (2009). Prevalence and type distribution of human papillomavirus in carcinoma and intraepithelial neoplasia of the vulva, vagina and anus: a meta-analysis. Int J Cancer, 124, 1626-36.
  5. de Sanjose S, Alemany L, Ordi J, et al (2013). Worldwide human papillomavirus genotype attribution in over 2000 cases of intraepithelial and invasive lesions of the vulva. Eur J Cancer, 49, 3450-61.
  6. Del Pino M, Rodriguez-Carunchio L, Ordi J (2013). Pathways of vulvar intraepithelial neoplasia and squamous cell carcinoma. Histopathology, 62, 161-75.
  7. Gargano JW, Wilkinson EJ, Unger ER, et al (2012). Prevalence of human papillomavirus types in invasive vulvar cancers and vulvar intraepithelial neoplasia 3 in the United States before vaccine introduction. J Low Genit Tract Dis, 16, 471-9.
  8. Gravitt PE, Peyton C, Wheeler C, et al (2003). Reproducibility of HPV 16 and HPV 18 viral load quantitation using TaqMan real-time PCR assays. J Virol Methods, 112, 23-3.
  9. Guimera N, Lloveras B, Lindeman J, et al (2013). The occasional role of low-risk human papillomaviruses 6, 11, 42, 44, and 70 in anogenital carcinoma defined by laser capture microdissection/pcr methodology: results from a global study. Am J Surg Pathol, 37, 1299-310.
  10. Insinga RP, Liaw KL, Johnson LG, Madeleine MM (2008). A systematic review of the prevalence and attribution of human papillomavirus types among cervical, vaginal, and vulvar precancers and cancers in the United States. Cancer Epidemiol Biomarkers Prev, 17, 1611-22.
  11. Kowalewska M, Szkoda MT, Radziszewski J, et al (2010). The frequency of human papillomavirus infection in polish patients with vulvar squamous cell carcinoma. Int J Gynecol Cancer, 20, 434-7.
  12. Li N, Franceschi S, Howell-Jones R, et al (2011). Human papillomavirus type distribution in 30,848 invasive cervical cancers worldwide: Variation by geographical region, histological type and year of publication. Int J Cancer, 128, 927-35.
  13. Natphopsuk S, Settheetham-Ishida W, Pientong C, et al (2013). Human papillomavirus genotypes and cervical cancer in northeast Thailand. Asian Pac J Cancer Prev, 14, 6961-4.
  14. Ngamkham J, Homcha-Aim P, Boonmark K, et al (2013). Preliminary study on human papillomavirus frequency and specific type-distribution in vulva cancer from Thai women. Asian Pac J Cancer Prev, 14, 2355-9.
  15. Pecorelli S (2009). Revised FIGO staging for carcinoma of the vulva, cervix, and endometrium. Int J Gynaecol Obstet, 105, 103-4.
  16. Pinto AP, Miron A, Yassin Y, et al (2010). Differentiated vulvar intraepithelial neoplasia contains Tp53 mutations and is genetically linked to vulvar squamous cell carcinoma. Mod Pathol, 23, 404-12.
  17. Pinto AP, Schlecht NF, Pintos J, et al (2004). Prognostic significance of lymph node variables and human papillomavirus DNA in invasive vulvar carcinoma. Gynecol Oncol, 92, 856-65.
  18. Riethdorf S, Neffen EF, Cviko A, et al (2004). p16INK4A expression as biomarker for HPV 16-related vulvar neoplasias. Hum Pathol, 35, 1477-83.
  19. Siriaunkgul S, Suwiwat S, Settakorn J, et al (2008). HPV genotyping in cervical cancer in Northern Thailand: adapting the linear array HPV assay for use on paraffin-embedded tissue. Gynecol Oncol, 108, 555-60.
  20. Skapa P, Zamecnik J, Hamsikova E, et al (2007). 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, 31, 1834-43.
  21. Smith JS, Backes DM, Hoots BE, et al (2009). Human papillomavirus type-distribution in vulvar and vaginal cancers and their associated precursors. Obstet Gynecol, 113, 917-24.
  22. Sutton BC, Allen RA, Moore WE, Dunn ST (2008). Distribution of human papillomavirus genotypes in invasive squamous carcinoma of the vulva. Mod Pathol, 21, 345-54.
  23. Swangvaree SS, Kongkaew P, Ngamkham J (2013). Frequency and type-distribution of human papillomavirus from paraffinembedded blocks of high grade cervical intraepithelial neoplasia lesions in Thailand. Asian Pac J Cancer Prev, 14, 1023-6.
  24. Tabbaa ZM, Gonzalez J, Sznurkowski JJ, et al (2012). Impact of the new FIGO 2009 staging classification for vulvar cancer on prognosis and stage distribution. Gynecol Oncol, 127, 147-52.
  25. van de Nieuwenhof HP, van Kempen LC, de Hullu JA, et al (2009). The etiologic role of HPV in vulvar squamous cell carcinoma fine tuned. Cancer Epidemiol Biomarkers Prev, 18, 2061-7.
  26. van der Avoort IA, Shirango H, Hoevenaars BM, et al (2006). Vulvar squamous cell carcinoma is a multifactorial disease following two separate and independent pathways. Int J Gynecol Pathol, 25, 22-9.
  27. van der Steen S, de Nieuwenhof HP, Massuger L, et al (2010). New FIGO staging system of vulvar cancer indeed provides a better reflection of prognosis. Gynecol Oncol, 119, 520-5.
  28. Wilkinson EJ, Teixeira MR (2003). Tumors of the vulva. Epithelial tumors. In 'Pathology and genetics of tumours of the breast and female genital organs. World Health Organization Classification of tumours'. Eds Tavassoli FA, Devilee P). Lyon: IARC Press, 316-25.

Cited by

  1. Prevalence of High Risk Human Papillomavirus Infection with Different Cervical Cytological Features among Women Undergoing Health Examination at the National Cancer Institute, Thailand vol.15, pp.14, 2014,
  2. Type-specific Prevalence of Human Papillomavirus by Cervical Cytology among Women in Brasov, Romania vol.15, pp.16, 2014,
  3. Expression in Squamous Cell Carcinomas of the Vagina and the Vulva in Tunisian Women vol.15, pp.24, 2015,
  4. "Histological characteristics of HPV-associated and -independent squamous cell carcinomas of the vulva: A study of 1,594 cases” vol.141, pp.12, 2017,
  5. Prevalence and type distribution of human papillomavirus in squamous cell carcinoma and intraepithelial neoplasia of the vulva vol.141, pp.6, 2017,
  6. Role of Human Papillomavirus in Vulvar Cancer vol.24, pp.4, 2017,
  7. Prevalence of human papillomavirus and its prognostic value in vulvar cancer: A systematic review and meta-analysis vol.13, pp.9, 2018,