Asian Pacific Journal of Cancer Prevention

Asian Pacific Journal of Cancer Prevention (아시아태평양암예방학회)
권호 표지
DOI QR코드

DOI QR Code

Prognostic Value of HPV18 DNA Viral Load in Patients with Early-Stage Neuroendocrine Carcinoma of the Uterine Cervix

  • Published : 2012.07.31
Download PDF
⟨ Previous Next ⟩

Abstract

Objectives: To evaluate the clinicopathologic correlation and prognostic value of HPV18 DNA viral load in patients with early-stage cervical neuroendocrine carcinoma (NECA). Methods: Formalin-fixed, paraffin-embedded tissue of cervical NECA patients with known HPV18 infection and clinicopathologic data including follow-up results were collected. The HPV18 DNA load was assessed with quantitative PCR targeting the HPV18 E6E7 region. Results: Twenty-one patients with early-stage (IB-IIA) cervical NECA were identified. HPV18 DNA viral load ranged from 0.83 to 55,174 copies/cell (median 5.90). Disease progression, observed in 10 cases (48%), was not significantly associated with any clinicopathologic variables. However, the group of patients with progressive disease tended to have a higher rate of pelvic lymph node metastasis (50% versus 9%, p=0.063) and a lower median value of HPV18 DNA viral load (4.37 versus 8.17 copies/cell, p=0.198) compared to the non-recurrent group. When stratified by a cut-off viral load value of 5.00 copies/cell, the group of patients with viral load ${\leq}5.00$ copies/cell had a significantly shorter disease-free survival than the group with viral load >5.00 copies/cell (p=0.028). The group with a lower viral load also tended to have a higher rate of disease progression (75% versus 31%, p=0.080). No significant difference in the other clinicopathologic variables between the lower and higher viral load groups was identified. Conclusion: HPV18 DNA viral load may have a prognostic value in patients with early-stage NECA of the cervix. A low viral load may be predictive of shortened disease-free survival in these patients.

Keywords

References

  1. Albores-Saavedra J, Gersell D, Gilks CB, et al (1997). Terminology of endocrine tumors of the uterine cervix: results of a workshop sponsored by the College of American Pathologists and the National Cancer Institute. Arch Pathol Lab Med, 121, 34-9.
  2. Cheung JL, Cheung TH, Ng CW, et al (2009). Analysis of human papillomavirus type 18 load and integration status from low-grade cervical lesion to invasive cervical cancer. J Clin Microbiol, 47, 287-93. https://doi.org/10.1128/JCM.01531-08
  3. Cohen MA, Basha SR, Reichenbach DK, Robertson E, Sewell DA (2008). Increased viral load correlates with improved survival in HPV-16-associated tonsil carcinoma patients. Acta Otolaryngol, 128, 583-9. https://doi.org/10.1080/00016480701558880
  4. Cooper K, Herrington CS, Stickland JE, Evans MF, McGee JO (1991). Episomal and integrated human papillomavirus in cervical neoplasia shown by non-isotopic in situ hybridisation. J Clin Pathol, 44, 990-6. https://doi.org/10.1136/jcp.44.12.990
  5. Datta NR, Kumar P, Singh S, et al (2006). Does pretreatment human papillomavirus (HPV) titers predict radiation response and survival outcomes in cancer cervix?--a pilot study. Gynecol Oncol, 103, 100-5. https://doi.org/10.1016/j.ygyno.2006.01.058
  6. de Boer MA, Jordanova ES, Kenter GG, et al (2007). High human papillomavirus oncogene mRNA expression and not viral DNA load is associated with poor prognosis in cervical cancer patients. Clin Cancer Res, 13, 132-8. https://doi.org/10.1158/1078-0432.CCR-06-1568
  7. Ersahin C, Szpaderska AM, Foreman K, Yong S (2005). Verucciform xanthoma of the penis not associated with human papillomavirus infection. Arch Pathol Lab Med, 129, e62-4.
  8. Gnanamony M, Peedicayil A, Subhashini J, et al (2009). Human papillomavirus types 16 and 18 mRNA levels and not DNA levels may be associated with advancing stages of cervical cancer. Int J Gynecol Cancer, 19, 1415-20. https://doi.org/10.1111/IGC.0b013e3181b62e05
  9. Gravitt PE, Burk RD, Lorincz A, et al (2003). A comparison between real-time polymerase chain reaction and hybrid capture 2 for human papillomavirus DNA quantitation. Cancer Epidemiol Biomarkers Prev, 12, 477-84.
  10. Hsieh PP, Tung CL, Chan AB, et al (2007). EBV viral load in tumor tissue is an important prognostic indicator for nasal NK/T-cell lymphoma. Am J Clin Pathol, 128, 579-84. https://doi.org/10.1309/MN4Y8HLQWKD9NB5E
  11. Kang WD, Kim CH, Cho MK, et al (2011). HPV-18 is a poor prognostic factor, unlike the HPV viral load, in patients with stage IB-IIA cervical cancer undergoing radical hysterectomy. Gynecol Oncol, 121, 546-50. https://doi.org/10.1016/j.ygyno.2011.01.015
  12. Kim JY, Park S, Nam BH, et al (2009). Low initial human papilloma viral load implicates worse prognosis in patients with uterine cervical cancer treated with radiotherapy. J Clin Oncol, 27, 5088-93. https://doi.org/10.1200/JCO.2009.22.4659
  13. Kim YM, Park JY, Lee KM, et al (2008). Does pretreatment HPV viral load correlate with prognosis in patients with early stage cervical carcinoma? J Gynecol Oncol, 19, 113-6. https://doi.org/10.3802/jgo.2008.19.2.113
  14. Mellin H, Dahlgren L, Munck-Wikland E, et al (2002). Human papillomavirus type 16 is episomal and a high viral load may be correlated to better prognosis in tonsillar cancer. Int J Cancer, 102, 152-8. https://doi.org/10.1002/ijc.10669
  15. Ohkubo K, Kato Y, Ichikawa T, et al (2002). Viral load is a significant prognostic factor for hepatitis B virus-associated hepatocellular carcinoma. Cancer, 94, 2663-8. https://doi.org/10.1002/cncr.10557
  16. Patel S, Chiplunkar S (2009). Host immune responses to cervical cancer. Curr Opin Obstet Gynecol, 21, 54-9. https://doi.org/10.1097/GCO.0b013e32831a9890
  17. Saunier M, Monnier-Benoit S, Mauny F, et al (2008). Analysis of human papillomavirus type 16 (HPV16) DNA load and physical state for identification of HPV16-infected women with high-grade lesions or cervical carcinoma. J Clin Microbiol, 46, 3678-85. https://doi.org/10.1128/JCM.01212-08
  18. 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. https://doi.org/10.1016/j.ygyno.2007.11.016
  19. Siriaunkgul S, Utaipat U, Settakorn J, et al (2011). HPV genotyping in neuroendocrine carcinoma of the uterine cervix in northern Thailand. Int J Gynecol Obstet, 115, 175-9. https://doi.org/10.1016/j.ijgo.2011.06.010
  20. Su JH, Wu A, Scotney E, et al (2010). Immunotherapy for cervical cancer: Research status and clinical potential. BioDrugs, 24, 109-29. https://doi.org/10.2165/11532810-000000000-00000
  21. Wells M, Ostor AG, Crum CP, et al (2003). Epithelial tumors. Tumors of the uterine cervix. In 'Pathology and genetics of tumours of the breast and female genital organs. World Health Organization Classification of tumour', Eds Tavassoli FA, Devilee P. IARC Press, Lyon pp 262-79.
  22. Woodman CB, Collins SI, Young LS (2007). The natural history of cervical HPV infection: unresolved issues. Nat Rev Cancer, 7, 11-22. https://doi.org/10.1038/nrc2050
  23. Xi LF, Koutsky LA, Castle PE, et al (2009). Human papillomavirus type 18 DNA load and 2-year cumulative diagnoses of cervical intraepithelial neoplasia grades 2-3. J Natl Cancer Inst, 101, 153-61. https://doi.org/10.1093/jnci/djn461
  24. Yoshida T, Sano T, Oyama T, Kanuma T, Fukuda T (2009). Prevalence, viral load, and physical status of HPV 16 and 18 in cervical adenosquamous carcinoma. Virchows Arch, 455, 253-9. https://doi.org/10.1007/s00428-009-0823-x

Cited by

  1. Genotype Distribution and Behavioral Risk Factor Analysis of Human Papillomavirus Infection in Uyghur Women vol.14, pp.10, 2013, https://doi.org/10.7314/APJCP.2013.14.10.5861
  2. A Novel Mutant of Human Papillomavirus Type 18 E6E7 Fusion Gene and its Transforming Activity vol.15, pp.17, 2014, https://doi.org/10.7314/APJCP.2014.15.17.7395
  3. Cervical Pathology in High-Risk Human Papillomavirus-Positive, Cytologically Normal Women vol.15, pp.18, 2014, https://doi.org/10.7314/APJCP.2014.15.18.7977
  4. Cross-reactivity profiles of hybrid capture II, cobas, and APTIMA human papillomavirus assays: split-sample study vol.16, pp.1, 2016, https://doi.org/10.1186/s12885-016-2518-4
  5. Type-dependent association between risk of cervical intraepithelial neoplasia and viral load of oncogenic human papillomavirus types other than types 16 and 18 vol.140, pp.8, 2017, https://doi.org/10.1002/ijc.30594
  6. Neuroendocrine carcinoma of the cervix: a systematic review of the literature vol.18, pp.1, 2018, https://doi.org/10.1186/s12885-018-4447-x