In a comprehensive review, Velentzis and colleagues addressed a very topical issue, namely the prophylactic use of the HPV vaccine after treatment for high-grade cervical intraepithelial neoplasia (CIN) . As pointed out by the authors, the percentage of recurrence of CIN2+ after treatment ranges from 2.5% to 18% [2, 3]. Furthermore, it is reported that up to 23.1% of women undergoing excisional treatment reveal positive surgical margins, which, in addition to the persistence of HPV infection, represent the two main predictors of disease recurrence . Finally, it is stressed that women treated for high-grade CIN are more at risk of subsequent cervical cancer than the general population for the next 10-25 years . Given the “numbers” mentioned above, the evaluation of a possible role of HPV vaccines to further reduce post-treatment CIN2+ has its rationale. The studies on the effectiveness of HPV vaccines after local treatment have been reported. In a non-randomized observational study including 737 women, Kang et al. showed a lower recurrence rate of high-grade lesions in vaccinated women (quadrivalent vaccine) than in non-vaccinated women (2.5% versus 7.2%, respectively) . Likewise, in a similar study, other authors found a decreased recurrence of CIN2+ in vaccinated women (quadrivalent vaccine) compared to non-vaccinated women in a sample of 350 patients (1.2% versus 6.4%, respectively) . The authors rightly conclude that, although there is evidence that the post-treatment HPV vaccine reduces recurrences, the lack of a randomized controlled trial represents a significant gap.
This is a fascinating article addressing a topic of keen interest based on the evidence present in the literature. Women undergoing excisional treatment for high-grade CIN represent a high-risk group of patients with cervical disease . Besides, women with disease recurrence are particularly sensitive to post-treatment HPV infections . The latter could be infections due to incomplete excision of the primary cervical lesion or by new acquisition. To date, there is indirect evidence on the efficacy of the post-treatment HPV vaccine . The absence of a randomized controlled trial on this topic represents a relevant gap that needs to be filled . In this regard, the NOVEL trial, scheduled to begin on November 1, 2019, and will be completed on July 31, 2023 (https://clinicaltrials.gov/ct2/show/NCT03979014) will hopefully shed some light on the subject. An Italian randomized controlled trial (HOPE9, https://clinicaltrials.gov/ct2/show/NCT03848039?term=ghelardi&rank=1), the aim of which is to evaluate the efficacy of 9-valent HPV vaccination in preventing recurrence of CIN2+ in participants treated for high-grade CIN, is also under way. It will be interesting to know if the vaccination is cost-effective for all women undergoing local treatment, or only for those women with post-treatment negative HPV. However, in the meantime, while awaiting the results of these studies, post-treatment HPV vaccination should be offered to women, provided that a correct counselling is made about the available evidence of efficacy.
Woman’s Health Sciences Department, Gynecologic Section, Polytechnic University of Marche, Ancona, Italy.
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