ICRH Kenya

Natural history and role of HPV in recurrence of dysplasia after treatment of precancerous lesions of the cervix

Team members:
Patricia Claeys; Annelies Aerssens; Marleen Temmerman;

OBJECTIVES

  • To describe the natural history of HPV infection in women who have been treated for CIN
  • To assess the relevance of persistent HPV infection in women as a prognostic marker for recurrence after treatment for CIN.

METHODS

  • Women, as well as their partners, who attended the colposcopy clinic in the University Hospital in Ghent, Belgium, in San Juan del Sur, Nicaragua, were invited to participate in the study.
  • HPV, through PCR-testing, was determined before and after treatment.
  • Cryotherapy was provided for treatment of CIN1 lesions and leep for treatment of CIN2/3 lesions
  • Follow-up visits were sheduled at 6 weeks, 6 monhts, 1 year and 2 year
  • At each visit, a Pap smear and a HPV test were taken and a colposcopy performed
  • Women with persisitent or recurrent CIN2/3 were re-treated

RESULTS

  • In Nicaragua, follow-up results are available for 122 women with CIN lesions. Fifty-five patients with CIN1 and 69 with CIN2-3 were treated with cryotherapy and loop electrosurgical excision procedure (LEEP), respectively. We report on 373 follow-up visits, 206 in the LEEP- and 167 in the cryotherapy group. For both treatment groups, presence of HPV strongly varied over time, with 62 high-risk positive women out of 67 in the LEEP group and 38 positive out of 55 in the cryotherapy group (p=0.001) at baseline. Immediately after treatment, a strong decrease in presence of HPV was observed in both groups. Over time, clearance continued and was non-significantly (p=0.50) faster in the cryotherapy group when compared to the LEEP group. Approximately the same detection rates were obtained for persistence of all HPV types and for high-risk types separately: 43% in the cryotherapy group versus 24% in the LEEP group, 38% versus 21.5%, 31% versus 18% and 20% versus 13% at 6 weeks, 6 months, 1 year and 2 years respectively.
  • Of the 138 belgian and nicaraguan women with CIN2/3 lesion, treated with loop electrosurgical excision procedure (LEEP), 117 (85%) tested positive for HPV, 15 (11%) tested negative. High-risk types were found in 108 cases (92.3%), only 2 were low-risk types (1.7%) and 7 (6%) were of an unknown HPV type (‘X’). Thirteen patients (9.4%) developed residual/recurrent disease during follow-up. Eleven of these 13 women were infected with a high-risk HPV type before treatment, 2 women tested negative before treatment. At time of recurrence, 7 women were still infected with the same HPV type, 2 were reinfected with another high-risk type and 2 were HPV negative. Cytology at 6 weeks was a good predictor for residual/recurrent disease. Nine out of 37 patients with abnormal cytology at 6 weeks had recurrent disease versus 3 out of 70 with a normal cytology (DOR: 7.18, 95%CI: 1.81-28.51, p=0.003). Sensitivity of this test was 75%, specificity 70.5%, PPV 24% and NPV 96%. The best prediction is made by using the combination of cytology and high-risk HPV within the first 6 months: out of the 54 women with abnormal cytology and/or high-risk HPV presence within the first 6 months, 11 developed residual/recurrent disease (DOR 10.23; 95%CI: 2.17-48.28). Sensitivity of this combination was 85%, specificity 65%, PPV 20%, NPV 97.5%.
  • Results on HPV prevalence in Belgian and Nicaraguan populations were published in international journals: Cytopathology. 2005 Aug;16(4):199-205 and Sex Transm Infect. 2006 Aug;82(4):334-6
  • Results on clearance of HPV were submitted to the journal Histopathology and on predictive value of HPV to the journal Cytopathology.