Possible Epithelial Ovarian Cancer Association with HPV18 or HPV33 Infection

  • Zhang, Pei-Pei (Medical College, Jishou University) ;
  • Zhou, Lei (Medical College, Hunan Normal University) ;
  • Cao, Jia-Shi (Medical College, Hunan Normal University) ;
  • Li, Yi-Ping (Medical College, Hunan Normal University) ;
  • Zeng, Zhi (Medical College, Maternal and Child health Hospital of Hunan) ;
  • Sun, Ni (Medical College, Hunan Normal University) ;
  • Shen, Li (Medical College, Hunan Normal University) ;
  • Zhu, Hao-Yue (Medical College, Hunan Normal University) ;
  • Ruan, Yang (Medical College, Hunan Normal University) ;
  • Zha, Wen-Ting (Medical College, Hunan Normal University) ;
  • Wang, Xin-Yu (Medical College, Hunan Normal University) ;
  • Zhang, Ke-Qiang (Medical College, Hunan Cancer Hospital) ;
  • Zhang, Ran (Medical College, Jishou University)
  • 발행 : 2016.06.01


The present study was conducted to investigate the prevalence of HPV infection in epithelial ovarian cancer (EOC) in Hunan province. DNA samples were collected from paraffin embedded ovarian tissue from 322 patients with EOC, 99 with ovarian benign tumors and 199 normal persons. The polymerase chain reaction and direct sequencing were used to identify the HPV types in the samples. The relationship between the infection of human papillomavirus (HPV) and the epithelial ovarian carcinoma (EOC) was investigated combined with clinical data. The prevalence of HPV18 and HPV33 in EOC group and benign group was higher than in the normal group. HPV18 and HPV33 may play a role in the development of both EOC and ovarian benign tumor and may participate in the development of EOC with traditional risk factors, family history and abortion, possibly exerting synergistic effects.


연구 과제 주관 기관 : National Natural Science Foundation of China


  1. Atalay F, Taskiran C, Taner MZ, et al (2007). Detection of human papillomavirus DNA and genotyping in patients with epithelial ovarian carcinoma. J Obstet Gynaecol Res, 33, 823-8. https://doi.org/10.1111/j.1447-0756.2007.00663.x
  2. Barbosa MS, Schlegel R (1989). The E6 and E7 genes of HPV-18 are sufficient for inducing two-stage in vitro transformation of human keratinocytes. Oncogene, 4, 1529-32.
  3. Bast RJ, Xu FJ, Yu YH, et al (1998). CA 125: the past and the future. Int J Biol Markers, 13, 179-87. https://doi.org/10.1177/172460089801300402
  4. Braem MG, Onland-Moret NC, Schouten LJ, et al (2012). Multiple miscarriages are associated with the risk of ovarian cancer: results from the european prospective investigation into cancer and nutrition. PLoS One, 7, 37141. https://doi.org/10.1371/journal.pone.0037141
  5. Cardiff. Familial Breast Cancer (2013). Classification and care of people at risk of familial breast cancer and management of breast cancer and related risks in people with a family history of breast cancer. national collaborating centre for cancer (UK).
  6. Chih-Ming, Ho S F C C (2012). Isolation and characterization of stromal progenitor cells from ascites of patients with epithelial ovarian adenocarcinoma. Hoet al. J Biomedical Sci, 19.
  7. Chyong-Huey Lai, SHCL (1992) Human papillomavirus in benign and malignant ovarian and endometrial tissues. Int J Gynecological Pathol, 7, 210-5.
  8. Dalla Torre D, Burtscher D, Edlinger M, et al (2014). Comparison of the prevalence of human papilloma virus infection in histopathologically confirmed premalignant oral lesions and healthy oral mucosa by brush smear detection. Oral Surg Oral Med Oral Pathol Oral Radiol, 119, 333-9.
  9. Dona MG, Ronchetti L, Giuliani M, et al (2013). Performance of the linear array HPV genotyping test on paired cytological and formalin-fixed, paraffin-embedded cervical samples[J]. J Molecular Diagnostics, 15, 373-9. https://doi.org/10.1016/j.jmoldx.2013.01.002
  10. G V M Berlin (2009). HPV type 18 is more oncopotent than HPV16 in uterine cervical carcinogenesis although HPV16 is the prevalent type in Chennai, India. Indian J Cancer, 46, 203-7. https://doi.org/10.4103/0019-509X.52954
  11. Geva E, Jaffe RB (2000). Role of vascular endothelial growth factor in ovarian physiology and pathology. Fertil Steril, 74, 429-38. https://doi.org/10.1016/S0015-0282(00)00670-1
  12. Giordano G, D'Adda T, Gnetti L, et al (2008). Role of human papillomavirus in the development of epithelial ovarian neoplasms in Italian women. J Obstet Gynaecol Res, 34, 210-7. https://doi.org/10.1111/j.1447-0756.2008.00759.x
  13. Ho CM, Chang SF, Hsiao CC, et al (2014). Potential application of curcumin and its analogues in the treatment strategy of patients with primary epithelial ovarian cancer. Int J Mol Sci, 15, 21703-22. https://doi.org/10.3390/ijms151221703
  14. Hu Z, Zhu D, Wang W, et al (2015). Genome-wide profiling of HPV integration in cervical cancer identifies clustered genomic hot spots and a potential microhomology-mediated integration mechanism. Nat Genet, 47, 158-63. https://doi.org/10.1038/ng.3178
  15. Jang J H, Cotterchio M, Gallinger S, et al (2009). Family history of hormonal cancers and colorectal cancer risk: A case-control study conducted in Ontario. Int J Cancer, 125, 918-25. https://doi.org/10.1002/ijc.24385
  16. Khanra K, Panda K, Mitra AK, et al (2012). Exon 8-9 Mutations of DNA Polymerase ${\beta}$ in Ovarian Carcinoma Patients from Haldia, India. Asian Pac J Cancer Prev, 13, 4183-6. https://doi.org/10.7314/APJCP.2012.13.8.4183
  17. Lauren G. Aoude K W A B (2013). A BAP1 mutation in a danish family predisposes to uveal melanoma and other cancers. Plos One, 8, 72144. https://doi.org/10.1371/journal.pone.0072144
  18. Liao X Y, Huang GJ, Gao C, et al (2014). A meta-analysis of serum cancer antigen 125 array for diagnosis of ovarian cancer in Chinese. J Cancer Res Ther, 10, 222-4. https://doi.org/10.4103/0973-1482.145884
  19. Linxweiler M, Bochen F, Wemmert S, et al (2015). Combination of p16 -Ki67 immunocytology and hpv polymerase chain reaction for the noninvasive analysis of HPV involvement in head and neck cancer. Cancer Cytopathol, 123, 219-29. https://doi.org/10.1002/cncy.21512
  20. Marchetti C, De Felice F, Palaia I, et al (2014). Risk-reducing salpingo-oophorectomy: a meta-analysis on impact on ovarian cancer risk and all cause mortality in BRCA 1 and BRCA 2 mutation carriers. BMC Womens Health, 14, 150. https://doi.org/10.1186/s12905-014-0150-5
  21. Meshkat M, Tayyebi Meibodi N, Sepahi S, et al (2014). The frequency of human papillomaviruses in colorectal cancer samples in Mashhad, northeastern Iran. Turk J Med Sci, 44, 501-3. https://doi.org/10.3906/sag-1303-81
  22. Michaelsen SH, Larsen CG, von Buchwald C (2014). Human papillomavirus shows highly variable prevalence in esophageal squamous cell carcinoma and no significant correlation to p16INK4a overexpression: a systematic review. J Thorac Oncol, 9, 865-71. https://doi.org/10.1097/JTO.0000000000000166
  23. Olaitan A, Doufekas K (2014). Clinical epidemiology of epithelial ovarian cancer in the UK. Int J Women's Health, 6, 537-45.
  24. Paris C, Pentland I, Groves I, et al (2015). CCCTC-binding factor recruitment to the early region of the human papillomavirus type 18 genome regulates viral oncogene expression. J Virol, 89, 4770-89. https://doi.org/10.1128/JVI.00097-15
  25. Park B, Cha M, Kim I (2014). Thioredoxin 1 as a serum marker for ovarian cancer and its use in combination with CA125 for improving the sensitivity of ovarian cancer diagnoses. Biomarkers, 19, 604-10. https://doi.org/10.3109/1354750X.2014.956793
  26. Qin Q, Gao F, Jiang W, et al (2014). Effect of neoadjuvant chemotherapy on expressions of estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2, and Ki-67 in breast cancer. Chin Med J (Engl), 127, 3272-7.
  27. Rakhshani N, Kalantari E, Bakhti H, et al (2014). Evaluation of HER-2/neu Overexpression in Gastric Carcinoma using a Tissue Microarray. Asian Pac J Cancer Prev, 15, 7597-602. https://doi.org/10.7314/APJCP.2014.15.18.7597
  28. Remmerbach TW, Brinckmann UG, Hemprich A, et al (2004). PCR detection of human papillomavirus of the mucosa: comparison between MY09/11 and GP5+/6 + primer sets. J Clin Virol, 30, 302-8. https://doi.org/10.1016/j.jcv.2003.12.011
  29. Romero-Pastrana F (2012). Detection and typing of human papilloma virus by multiplex PCR with type-specific primers. ISRN Microbiol, 2012, 1-5.
  30. Satpathy M, Zielinski R, Lyakhov I, et al (2015). Optical imaging of ovarian cancer using HER-2 affibody conjugated Nanoparticles. Methods Mol Biol, 1219, 171-85.
  31. Sawaya G F, Grady D, Kerlikowske K et al (1996). Antibiotics at the time of induced abortion: the case for universal prophylaxis based on a meta-analysis. Obstet Gynecol, 87, 884-90.
  32. Shirish Shukla, Gauri Shishodia, Sutapa Mahata (2010). Aberrant expression and constitutive activation of STAT3 in cervical carcinogenesis: implications in high-risk human papillomavirus infection. Molecular Cancer, 9, 1-17.
  33. Soper D E (2010). Pelvic inflammatory disease. Obstet Gynecol, 116, 419-28. https://doi.org/10.1097/AOG.0b013e3181e92c54
  34. Tommasino M (2014). The human papillomavirus family and its role in carcinogenesis. Semin Cancer Biol, 26, 13-2. https://doi.org/10.1016/j.semcancer.2013.11.002
  35. Tsilidis KK, Allen NE, Key TJ, et al (2011). Oral contraceptive use and reproductive factors and risk of ovarian cancer in the european prospective investigation into cancer and nutrition. Br J Cancer, 105, 1436-42. https://doi.org/10.1038/bjc.2011.371
  36. Watanabe T, Shibata M, Nishiyama H, et al (2013). Elevated serum levels of vascular endothelial growth factor is effective as a marker for malnutrition and inflammation in patients with ovarian cancer. Biomed Rep, 1, 197-201. https://doi.org/10.3892/br.2013.54
  37. Whittemore AS, Harris R, Itnyre J (1992). Characteristics relating to ovarian cancer risk: collaborative analysis of 12 US case-control studies. IV. The pathogenesis of epithelial ovarian cancer. Collaborative Ovarian Cancer Group. Am J Epidemiol, 136, 1212-20. https://doi.org/10.1093/oxfordjournals.aje.a116429
  38. Park B, Cha M, Kim I (2014). Thioredoxin 1 as a serum marker for ovarian cancer and its use in combination with CA125 for improving the sensitivity of ovarian cancer diagnoses. Biomarkers, 19, 604-10. https://doi.org/10.3109/1354750X.2014.956793