The study was intended to answer the question about changes in the cervical smear for HPV in HPV-positive patients after receiving the 9-valent HPV vaccine. The main result of the analysis was that in the vaccinated group the rate of HPV disappearance was significantly higher over the follow-up period than in the control group. This applies especially to the so-called complete remission, i.e., the complete disappearance of the HPV virus - it was observed in nearly ¾ of vaccinated women (72.4%) compared to less than half of unvaccinated patients (45.7%). This effect is especially visible when analyzing the disappearance of HPV genotypes covered by the 9-valent vaccine. Proportion of positive HPV Gardasil genotype after vaccination/observation was significantly higher in group with positive HPV Gardasil genotype before vaccination/observation (51.9% vs 0.0%, p = 0.001).
There are insufficient studies that could be related to our results. Just as the preventive effect of vaccination on the development of lesions has been proven, there are scientific reports showing the beneficial effect of vaccination on reducing the recurrence of HPV-related lesions. However, we have not been able to find any literature on the disappearance of HPV infection in the smear. Our previous analysis, including a smaller study group, showed the added value of vaccination in the group of HPV-positive patients [11].
Vaccination can reasonably be expected to prevent new HPV infections caused by different HPV types, as well as reinfections with the same HPV type. This protection applies to new exposures from infected partners and to autoinoculation from adjacent or distant sites that are already productively infected. Since the recurrence rate of HSIL after surgical treatment is still over 6%, it means that only eliminating or neutralizing the HPV virus gives a chance to reduce the percentage []. Persistent infection with a highly oncogenic HPV genotype is the only modifiable risk factor for pre- and cancer-related conditions. However, the mechanism of function of the HPV vaccine in patients already infected with HPV is still not fully understood.
Konstantinos S Kechagias with co-authors presented systematic review and meta-analysis on the role of HPV vaccination at the time of local surgical treatment for cervical and other diseases related to HPV infection, with rigorous methodological assessment of risk of bias, heterogeneity, and appropriate data. The researchers revealed that the risk of recurrence of CIN2 + was reduced in vaccinated patients who were vaccinated compared with those who were not vaccinated (according to data collected from 11 articles). Interestingly, the effect estimate was stronger when the risk of recurrence of CIN2 + was assessed for disease related to HPV subtypes HPV16 or HPV18. The risk of recurrence of CIN3 was also reduced in vaccinated patients []. The authors' conclusions that the impact on reducing the recurrence of lesions associated with the presence of HPV 16 and 18 may be related to the fact that the availability of bivalent and quadrivalent vaccinations was the highest a few or a dozen years ago. Perhaps, thanks to the increasing availability of the 9-valent vaccine, in a dozen or so years we will be able to present a meta-analysis covering the disappearance of CIN 2 + lesions associated with other genotypes covered by the vaccine.
In addition to the potential effect of HPV vaccination on reducing the risk of cervical recurrence, studies have shown a beneficial effect on HPV-dependent, non-oncogenic lesions, such as recurrent laryngeal papillomatosis or condyloma acuminata. Researchers also attempted to assess the impact of vaccination in other, less common HPV-related diseases, affecting the vulva or vagina. Testing for the presence of HPV DNA in a cervical smear is currently the only screening method allowing early detection of changes in the vagina or vulva. Evidence shows that prophylactic HPV vaccination, as in the case of cervical cancer precursors, also prevents HPV-related vulvar and vaginal HPV-associated precancers [9,10].
Several studies suggested that HPV vaccination has a statistically significant impact in reducing post-surgical recurrent disease both in women and men exposed to previous HPV infection [12, 13, 14]. In 2012, Joura et al. reported that HPV vaccination among women after surgical treatment for HPV-related disease significantly reduced the incidence of subsequent significant impact of adjuvant HPV vaccination in reducing the risk of recurrence of genital warts after initial surgical treatment [13]. In 2021, Ghelardi et al. documented the effectiveness of HPV vaccine in preventing recurrent disease after surgical treatment for vulvar high-grade squamous intraepithelial lesions [14]. There are discussions in extensive reviews about the reduced risk of recurrence of CIN lesions [15, 16] however, the time of administering the vaccine peri- or post-procedure has not been standardized and there are no clear guidelines on when it should be administered.
A similar analysis was presented by the authors of the publication in 2023, in which they described the evidence for using prophylactic HPV vaccines in patients with HPV-associated disease before, during, or after treatment. The researchers discussed potential mechanisms by which individuals with HPV-associated disease may or may not benefit from prophylactic vaccines [17].
More and more doctors and scientific societies encourage the vaccination of an increasingly older patient population. The American Society for Colposcopy and Cervical Pathology recommends adherence to current CDC recommendations for vaccination of individuals aged 9 to 26 years and consideration of the possible benefit of adjuvant HPV vaccination during shared decision making for previously unvaccinated individuals aged 27 to 45 years who are undergoing treatment for CIN2+ [18].
Our previous work on the immune response confirms a higher titer of anti-HPV antibodies in post-vaccination patients who remain infected with HPV [19] but there are no scientific studies to date that describe the disappearance of infection in cervical smears.
Our study group is under strict supervision, but observations made after more than a decade will certainly be interesting. The question remains whether in the future HPV- positive patients will experience a recurrence of SIL-type lesions in the cervix or lesions in the vagina and vulva.