Safety and efficacy of a therapeutic HPV vaccine in high-grade anal intraepithelial neoplasia

A therapeutic human papillomavirus (HPV)-16 vaccine appeared to be safe in a population of HIV-positive men who have sex with men with high-grade anal intraepithelial neoplasia (AIN). In the highest dose group of the phase 1/2 VACCAIN-T trial, the clinical response rate was 40%.

“Although anal cancer is rare, the incidence is rising, and the morbidity and mortality are high,” expressed Dr Karien Gosens (Mauritskliniek, the Netherlands) [1]. “Anal cancer is a squamous cell carcinoma, and the underlying cause is usually a high-risk HPV infection.” Dr Gosens further explained that low-grade AIN generally does not lead to anal cancer, whereas individuals with high-grade AIN are at risk of developing it. HIV-positive men who have sex with men have the highest risk of anal cancer, but women with vulvar cancer have an increased risk of anal cancer as well [2].

“From the ANCHOR trial, we have learned that actively treating high-grade AIN leads to a 57% reduction of anal cancer compared with a close monitoring approach among HIV-positive men above 35 years of age,” said Dr Gosens [1,3]. Therefore, treating all high-grade AIN in this population is advised.

“However, the screening for AIN is time-consuming and difficult to endure for patients,” highlighted Dr Gosens. Moreover, the currently available therapies are not always effective, and responders frequently have recurrences within 2 years [4,5]. In the Netherlands, prophylactic vaccines are available, protecting against high-risk HPV viruses, such as HPV-16 and HPV-18. “Unfortunately, these vaccines do not work in patients with high-grade AIN,” added Dr Gosens. The research team wondered whether a therapeutic vaccine could help to treat patients with established high-grade AIN [6]. Since 67% of anal cancers are caused by HPV-16, Dr Gosens and colleagues directed their efforts toward investigating a therapeutic vaccine targeting this HPV variant [6,7].

A therapeutic HPV-16 vaccine had already been tested for patients with high-grade vulvar intraepithelial neoplasia, with good results [8]. In the current dose-finding phase 1/2 trial, called VACCAIN-T, HIV-positive men who have sex with men with recurrent or persistent high-grade AIN caused by HPV-16 (n=40) received 3 to 4 intracutaneous vaccines at 4 dose levels [6]. The outcome measures were safety, HPV-16-specific immune response, and regression of high-grade AIN after 3, 6, 12, and 18 months. Of note, adjuvant peginterferon-α was delivered to half of the participants.

“Most participants had transient grade 1 or 2 adverse events in the first week after vaccination,” said Dr Gosens. Fatigue occurred in 70% of the participants who did not receive peginterferon-α and in 100% of those who did receive peginterferon-α. Flu-like complaints were observed in 75% of the participants in the peginterferon-α group and 0% in the non-peginterferon-α group. One vaccine-related grade 3 adverse event was reported: a type 1 reaction with exanthema and gastrointestinal complaints.

The clinical response rate at 18 months was 24%, with the highest response rate in the highest dose level group (40%; see Figure). Moreover, the highest immune response was observed in participants in the highest dose group, a result comparable with findings of the previous trial involving participants with high-grade vulvar intraepithelial neoplasia [8]. Finally, peginterferon-α did not lead to an increased immune response [6].

Figure: Clinical response rates with therapeutic vaccine [1]



“This was a small dose-finding trial,” commented Dr Gosens. “In the future, we should consider more broadly applicable HPV vaccines, perhaps change the adjuvant treatment, and investigate mRNA vaccination techniques to improve the efficacy of vaccination among patients with high-grade AIN.”

1. Gosens KCM, et al. Therapeutic HPV-16 vaccination for anal intraepithelial neoplasia treatment. Dermatologendagen 2024, 11–12 April, Amsterdam, the
2. Clifford G, et al. Int J Cancer. 2021;148(1):38-47.
3. Palefsky JM, et al. N Engl J Med 2022;386:2273-2282.
4. Richel O, et al. Lancet Oncol. 2013;14(4):346-353.
5. Siegenbeek van Heukelom ML, et al. Am J Clin Dermatol. 2018;19(1):127-132.
6. Gosens KCM, et al. Clin Cancer Res. 2023 Oct 13;29(20):4109-4117.
7. Lin C, et al. Lancet Infect Dis. 2018;18(2):198-206.
8. Kenter GG, et al. 2009;361(19):1838-1847.

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Posted on 31 May 20244 June 2024