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

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.