Effect of Condom Use after CIN Treatment on Cervical HPV Biomarkers Positivity: Prolonged Follow Up Study

Abstract

Background: Several factors contribute in the cervical healing process following local surgical treatment; in a previous work our group has documented a beneficial mid-term role of regular condom use immediately postoperatively in terms of CIN relapse prevention and expression of active viral biomarkers. Materials and Methods: Aiming to investigate whether the favorable contribution of consistent condom use could be extrapolated in the longer term, we conducted a prospective single center observational study including women scheduled to undergo conservative excisional treatment for CIN (LLETZ procedure). In all women a strong recommendation for consistent use for the first 6 months was given. For 204 women who underwent the procedure and completed successfully the two-year follow up a complete dataset of HPV biomarkers’ results obtained six months and two years postoperatively was available. Patients were asked to complete a questionnaire to assess condom use compliance. A 90% compliance rate represented the threshold for consistent use. An LBC sample was obtained and tested for HPV genotyping, E6 & E7 mRNA by NASBA technique as well as flow cytometry, and p16 at 0 (pre-treatment), 6 and 24 months. HPV DNA and other related biomarkers status at 6 and 24 months, treatment failures at 24 months and condom use compliance rates represented study outcomes. Results: Six months post-operatively we documented a reduction in the rates of HPV DNA positivity, which was detected in only 23.2% of compliant condom users in comparison to 61.9% in the non-compliant group (p < 0.001, OR: 0.19, 95%CI: 0.1–0.36). For the HPV mRNA test, either assessed with the NASBA method or with flow cytometry, reduced positivity percentages were observed in the compliant group, in particular 1.6% vs. 8% for NASBA and 7.1% vs. 16.4% using flow cytometry, although these differences were not statistically significant (p = 0.1039 and 0.0791, respectively). Finally, reduced p16 positivity rates were documented in the compliant group. At the two year follow up, a more pronounced difference in HPV DNA positivity rates was observed, specifically only 13% positivity among the compliant women compared with 71% of the non-compliant (p < 0.0001); this illustrates a further decreasing trend compared with the 6th month in the compliant group as opposed to an increasing tendency in the non-compliant group, respectively (difference: 9.0%, 95% CI: 0% to 20.6%, p = 0.1523). At that time, 80% of the failed treatments were HPV mRNA positive compared to 10% positivity for the cases treated successfully (OR: 34, 95%CI: 6.8–173, p < 0.0001), a finding indicative that HPV mRNA E6 & E7 positivity accurately predicts treatment failure; p16 positivity was also observed at higher rates in cases with treatment failure. Conclusions: Consistent condom use following conservative excisional CIN treatment appears to significantly reduce rates of CIN recurrence and biomarkers of HPV expression. Additional HPV vaccination at the time of treatment could further enhance the positive effect of consistent condom use.

High prevalence of high‐risk HPV genotypes in individuals attending an infectious diseases clinic from 2018 to 2022 in Milan, Italy

“…23 Along with HPV 16, HPV 18 and 6, all targeted from vaccination, have been reported as the most common types in cervix and anus of women and men. 24,25 In addition to vaccination, the consistent condom use in women might improve HPV clearance and prognosis, as observed by Valasoulis et al 26 Our data show a high rate of HPV genotypes multiple infections, without significant differences over the years: specifically, every year 37%-43% of patients attending our clinic resulted positive for ≥2 HR types. This could be explained by the fact that HPV types share risk determinants like sexual activity and age, thus multiple infections should be expected.…”

“…Along with HPV 16, HPV 18 and 6, all targeted from vaccination, have been reported as the most common types in cervix and anus of women and men 24,25 . In addition to vaccination, the consistent condom use in women might improve HPV clearance and prognosis, as observed by Valasoulis et al 26 …”

The residual rate of HPV and the recurrence rate of CIN after LEEP with negative margins: A meta-analysis

“…A study has shown that consistent condom use after LEEP significantly reduces HPV-positive rates and also appears to significantly reduce rates of CIN recurrence and biomarkers of HPV expression. Additional HPV vaccination administered at the time of treatment could further enhance the positive effects of consistent condom use [ 24 , 25 ].…”

HPV-Based Self-Sampling in Cervical Cancer Screening: An Updated Review of the Current Evidence in the Literature

“…With comparable clinical accuracy for hrHPV testing in self-samples as clinician-collected material and flexibility for use both in primary cervical screening as well as triage of abnormal samples, advocacy for incorporating self-sampling into organized screening programs is strong, especially after the disruption due to the SARS-CoV-2 pandemic [ 5 , 17 , 20 , 21 , 57 , 58 , 59 , 60 ]. With an ever-growing number of countries considering self-collection for cervical screening, issues to be determined are how to best offer the service, whom to offer it to, adhering to f-u, triage of HPV-positive cases and how to best prepare the public and health systems for this transition [ 14 , 61 ]…”