Abstract

To evaluate the clinicopathologic correlation and prognostic value of HPV18 DNA viral load in patients with early-stage cervical neuroendocrine carcinoma (NECA). 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. 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 ≤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. THPV18 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.

Highlights

  • Cervical carcinoma is associated with human papillomavirus (HPV) infection (Woodman et al, 2007)

  • HPV18 DNA viral load may have a prognostic value in patients with early-stage neuroendocrine carcinoma (NECA) of the cervix

  • In nasal NK/Tcell lymphoma, a low viral load of Epstein-Barr virus detected in formalin-fixed paraffin-embedded tissue was reported to be associated with better overall survival of the patients, compared to the high viral load (Hsieh et al, 2007)

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Summary

Introduction

Cervical carcinoma is associated with human papillomavirus (HPV) infection (Woodman et al, 2007). Squamous cell carcinoma and adenoarcinoma are the most common subtypes of cervical cancer and comprise the large majority of cases. Neuroendocrine carcinoma (NECA) is a rare and aggressive subtype of cervical carcinoma with a worse prognosis than the other subtypes (Wells et al, 2003). The distribution of HPV types is variable in different subtypes of cervical carcinoma. HPV16 is the predominant type detected in almost 60% of cases, whereas HPV18 infection is much less common (Siriaunkgul et al, 2008). HPV18 infection is detected in a significant proportion of cases, which is only slightly lower than that of HPV16 infection. In NECA, HPV18 is the most prevalent HPV type, found in 75% of cases (Siriaunkgul et al, 2011)

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