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

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.