Genotyping and viral load dynamics in residual tumor tissue after chemoradiation therapy for HPV-positive anal cancer

Purpose of the study. To establish the causes of tumor tissue infection in anal cancer with human papillomavirus (HPV), its typical diversity, to determine the relationship between virological response (VR) and complete clinical response (CCR), overall survival (OS) and event-free survival (EFS).

Patients and methods. A total of 41 patients were examined: 36 women (57.1 ± 8.8 years) and 5 men (55 ± 9.5 years) with squamous cell anal cancer; IA–II – 31.7 %, III–IIIA – 24.4 %, IIIB – 43.9 %. The patients underwent conformal radiation therapy to the tumor and lymph collector against the background of chemotherapy (mitomycin, capecitabine). Scrapings from the tumor surface were collected before chemoradiotherapy, upon its completion, after 3 and 6 months. HPV DNA of 14 types was detected by polymerase chain reaction PCR. VR was considered the elimination of HPV in the residual tumor tissue. VR was compared with the indicators of CCR, OS and EFS. Statistical processing was performed using the STATISTICA 10.0 program.

Results. HPV-positive status was confirmed in 34 patients (82.9 %), whereas 7 patients (17.1 %) were HPV-negative. In 73.5 % of HPV+ tumor samples, the virus was in the form of mono-, in 26.5 % – mixed infection. The most frequently detected types of the virus were 16 (82.4 %), 18 (17.6 %) and 31 (8.8 %). Immediately after chemoradiotherapy, HPV+ were 53.8 %, after 3 months – 35.7 %, after 6 months – 34.6 % of patients. Patients with VR achieved CCR in 88.2 % of cases, without VR – 45.5 % (p = 0.0022). In the group with VR, 3‑year EFS was 88.2 %, without VR – 27.3 % (p = 0.00048).

Conclusion. The study demonstrates the clinical potential of HPV DNA detection in residual tumor tissue for assessing the effectiveness of chemoradiotherapy in locally advanced anal cancer. Patients with VR more often achieved PCR and had a higher 3‑year EFS. When assessing the prognosis of chemoradiotherapy effectiveness, it is useful to take into account VR and assess it simultaneously with the assessment of CCR, and to include in the examination plan the analysis of tumor tissue for HPV DNA of a wide range of types during primary diagnostics.

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