Assessment of Mitotic Count and Multinucleated Tumor Cells in HPV-Associated and HPV-Independent Vulvar Carcinoma

Squamous cell carcinomas of the vulva are classified into human papillomavirus (HPV)- associated and HPV-independent types. The mechanisms of carcinogenesis at this site remain poorly understood. The aim of the study is to compare mitotic activity and the number of multinucleated tumor cells in HPV-associated and HPV-independent vulvar carcinoma. Material and methods. This retrospective study included 74 patients with newly diagnosed vulvar squamous cell carcinoma. Immunohistochemical analysis and viral typing using polymerase chain reaction were performed. Quantification of mitotic figures (including atypical forms) and multinucleated tumor cells was conducted in 20 consecutive ×400 magnification fields. Evaluation included 74 tumor specimens and 18 matched normal tissue controls. Results. We observed HPV-positive status in 21 cases (28.4%), with 53 tumors (71.6%) classified as HPV-negative. HPV-positive patients showed younger age at diagnosis (65 [57–76] years) compared to HPV-negative cases (75 [68–82] years). HPV- associated tumors were diagnosed at earlier disease stages (Stage I-II) in 71.4% of cases compared to HPV- independent vulvar carcinomas (47% at Stage I-II). HPV-positive tumors demonstrated significantly elevated mitotic activity (37 [31.25–46.00]) versus HPV-negative cases (16.5 [12.00–24.25]); p<0.001) and normal controls (2.0 [1.00–3.00]). The count of atypical mitoses was significantly higher in HPV-positive tumors (15.5 [10.00–20.00]) compared to HPV-negative cases (p<0.001). The count of binucleated or multinucleated tumor cells was lower in HPV-independent carcinogenesis (4.0 [2.00–8.25]) compared to virus-associated tumors (24.5 [23.25–32.75]). HPV-associated mitotic figures were identified in 85.7% (n=18) of HPV-positive vulvar carcinoma samples. Conclusion. HPV infection results in abnormal mitoses and development of multinucleated malignant cells. HPV-driven tumors display pathognomonic aberrant mitoses with extrachromosomal chroma- tin fragments adjacent to the central spindle. HPV-associated tumors demonstrate enhanced radiosensitivity, likely due to their characteristic chromosomal instability and defective DNA repair mechanisms. Conclusion. HPV infection results in abnormal mitoses and development of multinucleated malignant cells. HPV-driven tumors display pathognomonic aberrant mitoses with extrachromosomal chromatin fragments adjacent to the central spindle. HPV-associated tumors demonstrate enhanced radiosensitivity, likely due to their characteristic chromosomal instability and defective DNA repair mechanisms.

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