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Undetected human papillomavirus DNA and uterine cervical carcinoma

Association with cancer recurrence

Unentdeckte humane Papillomavirus-DNA und Zervixkarzinom

Zusammenhang mit einem Krebsrezidiv

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Abstract

Background

The time course of human papillomavirus (HPV) DNA clearance was studied in patients with carcinoma of the cervix during follow-up after primary radical radiotherapy (RT). This study investigated the relationship between timing of HPV clearance and RT effectiveness.

Patients and methods

A total of 71 consecutive patients who were treated for cervical cancer with primary radical radiotherapy and high-dose rate intracavitary brachytherapy with or without chemotherapy were enrolled in the study. Samples for HPV DNA examination were taken before (1) treatment, (2) every brachytherapy, and (3) every follow-up examination. The times when HPV DNA was undetected were analyzed for association with recurrence-free survival.

Results

HPV DNA was not detected in 13 patients (18 %) before RT. Of the 58 patients with HPV DNA detected before treatment, HPV DNA was not detected in 34 % during treatment and in 66 % after the treatment. Within 6 months after RT, HPV DNA was detected in 0 % of all patients. The patients were followed up for a median period of 43 months (range 7–70 months). In all, 20 patients were found to develop recurrence. The 3-year cumulative disease-free survival (DFS) rate was 71 ± 5.4 % for all 71 patients. In multivariate analysis, DFS was significantly associated with HPV (detected vs. not detected) with a hazard ratio of 0.07 (95 % confidence interval 0.008–0.6, p = 0.009).

Conclusion

In this study, patients in whom HPV was not detected had the worst prognosis. Six months after RT, HPV DNA was detected in 0 % of the patients. Patients in whom HPV DNA could not be detected before treatment need careful follow-up for recurrence and may be considered for additional, or alternative treatment.

Zusammenfassung

Ziel

Gegenstand der Untersuchung war der Zeitverlauf der Eliminierung von humaner Papillomvirus-(HPV-)DNA bei Patienten mit Zervixkarzinomen während der Nachfolgeuntersuchungen nach einer primären radikalen Strahlentherapie (RT). Diese Studie untersuchte den Zusammenhang zwischen dem Zeitpunkt der HPV-Eliminierung und der RT-Effizienz.

Patienten und Methoden

Insgesamt 71 aufeinanderfolgende Patienten, die mit einer primären RT behandelt wurden, nahmen an der Studie teil. Proben für HPV-DNA-Untersuchungen wurden 1) vor der Behandlung, 2) vor jeder Brachytherapie und 3) vor jeder Nachfolgeuntersuchung genommen. Die Fälle, bei denen keine HPV-DNA entdeckt wurde, wurden auf einen Zusammenhang zu rückfallfreiem Überleben analysiert.

Ergebnisse

Bei 13 Patienten (18 %) konnte keine HPV-DNA vor der RT festgestellt werden. Von den 58 Patienten, bei denen HPV-DNA vor der Behandlung identifiziert wurde, wurde die HPV-DNA bei 34 % nicht während der Behandlung und bei 66 % nicht nach der Behandlung entdeckt. Innerhalb von 6 Monaten nach der RT wurde die HPV-DNA bei keinem Patienten (0 %) festgestellt. Die Patienten wurden für eine durchschnittliche Zeitdauer von 43 Monaten (Spanne 7–70 Monate) weiterbetreut. Bei 20 Patienten trat ein Rückfall ein. Die 3-jährige kumulative krankheitsfreie Überlebensrate (DFS) war 71 ± 5,4 % für alle 71 Patienten. In einer multivariaten Analyse war DFS signifikant mit HPV verbunden (entdeckt vs. nicht entdeckt) mit einer Hazard-Ratio (HR) von 0,07 (95 %-KI 0,008–0,6; p = 0,009).

Schlussfolgerung

In dieser Studie hatten Patienten, bei denen HPV nicht entdeckt wurde, die schlechteste Prognose. Sechs Monate nach der RT wurde HPV-DNA bei 0 % der Patienten entdeckt. Patienten, bei denen vor der Behandlung keine HPV-DNA identifiziert werden konnte, sollten sorgfältig nachbeobachtet werden und für zusätzliche oder alternative Therapien in Erwägung gezogen werden.

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Authors and Affiliations

  1. Departments of Radiology, University of Tokyo Hospital, 7-3-1, Hongo, Bunkyou-ku, 113-8655, Tokyo, Japan

    Kae Okuma M.D., Ph.D., Hideomi Yamashita M.D., Ph.D. & Keiichi Nakagawa M.D., Ph.D.

  2. Departments Obstetrics and Gynecology, University of Tokyo Hospital, 7-3-1, Hongo, Bunkyou-ku, 113-8655, Tokyo, Japan

    Terufumi Yokoyama Ph.D. & Kei Kawana M.D., Ph.D.

Authors
  1. Kae Okuma M.D., Ph.D.
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  2. Hideomi Yamashita M.D., Ph.D.
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  3. Terufumi Yokoyama Ph.D.
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  4. Keiichi Nakagawa M.D., Ph.D.
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  5. Kei Kawana M.D., Ph.D.
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Correspondence to Kae Okuma M.D., Ph.D..

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Conflict of interest

K. Okuma, H. Yamashita, T. Yokoyama, K. Nakagawa, and K. Kawana state that there are no conflicts of interest.

All studies on humans described in the present manuscript were carried out with the approval of the responsible ethics committee and in accordance with national law and the Helsinki Declaration of 1975 (in its current, revised form). Informed consent was obtained from all patients included in studies.

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Okuma, K., Yamashita, H., Yokoyama, T. et al. Undetected human papillomavirus DNA and uterine cervical carcinoma. Strahlenther Onkol 192, 55–62 (2016). https://doi.org/10.1007/s00066-015-0909-0

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  • DOI: https://doi.org/10.1007/s00066-015-0909-0

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