HPV vaccines may help prevent recurrence of high-grade cervical dysplasia

The HPV vaccine is safe and effective for the prevention of cervical cancer when given prior to HPV infection. A study in the journal Vaccines adds to accumulating data that HPV vaccination may also help reduce cervical cancer rates in women who have been diagnosed with high-grade cervical dysplasia (HSIL). While the results were not statistically significant, vaccinating these patients may aid in reducing cervical cancers rates.

Giorgio Bogani, MD, PhD, of the gynecological oncology unit at Fondazione IRCCS Istituto Nazionale dei Tumori di Milano in Milan and colleagues conducted a retrospective, multi-institutional study in Italy. Researchers collected charts of 1,914 consecutive patients who were newly diagnosed with high grade cervical dysplasia, or HSIL, and undergoing conization from January 1, 2010, through December 31, 2014, and had 5 years of follow-up.

To be included in the study, patients had to be newly diagnosed with HSIL, have had an excisional procedure such as conization, and have that procedure performed with loop electrosurgical excision (LEEP). Other requirements included that patients’ conization procedure had to have been performed between 2010 and 2014, and patients had a 5-year follow-up without recurrence. Researchers noted that patients who experienced recurrence within the first 5 years were still included even if the 5-year follow-up was not completed.

Patients who were < 18 years of age, those who withdrew their consent, who underwent laser conization or cold knife conization, who had an ablative procedure, or who were diagnosed with invasive cancer at the time of conization were excluded from the study. Patients with glandular lesion, pregnancy, and hysterectomy were also not included.

Researchers compared recurrence rates in 116 patients who had vaccinations following conization (6.1%) and 1,798 patients who had conization alone (93.9%). Bogani and colleagues used a propensity-score matching algorithm to reduce allocation biases and used the Kaplan-Meir and Cox hazard models to estimate recurrence risk.

The study authors reported the 5-year recurrence rate as 1.7% (n=2) in the vaccinations group versus 5.7% (n=102) in the group that had not received vaccines following conization.

After researchers applied propensity-score matching, they selected 100 patients in the conization/vaccination group and 200 patients in the conization alone group. “The crude number of recurrences was 2 (2%) and 11 (5.5%) for patients undergoing conization plus vaccination and conization alone, respectively (p = 0.231),” Bogani and colleagues reported.¹ They said persistent lesions were not affected by vaccination. It did, however, reduce recurrence, which was defined by one or more negative exams between conization and recurrent cervical dysplasia diagnosis, they reported.

Bogani and colleagues cited past evidence that corroborates their findings, including 6 other studies.^2-7 For example, the Kang et al study (2013) reported lower recurrence rates in patients who had received the vaccination following LEEP: of 360 patients who had conization plus vaccination and 377 patients who had conization alone, the rates of recurrence were 2.5% and 7.2% respectively.² They noted the prospective, non-randomized SPERANZA project showed an 80% decrease in recurrence. For that study, the recurrence rate was 1% in the vaccinated group and 6% in conization alone.3 Petrillo et al (2020), Sand et al (2020), Paavonen et al (2009), and Del Pino et al (2020) also showed similar results.^4-7

While researchers said that there was indeed a slight reduction in recurrence, they acknowledged it was not statistically significant. In addition, researchers said “vaccination resulted in the only modifiable factor that might slightly reduce the recurrence rate.”¹ Patients who had low reported risk of lesion persistence seemed to benefit the most from vaccination. Bogani and colleagues concluded that more evidence is needed to see if vaccination after conization is cost-effective in the prevention of recurrence.

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References

1. Bogani G, Raspagliesi F, Sopracordevole F, et al. Assessing the long-term role of vaccination against HPV after loop electrosurgical excision procedure (LEEP): a propensity-score matched comparison. Vaccines (Basel). 2020;8(4):717. Published 2020 Dec 1. doi:10.3390/vaccines8040717. Accessed 6 January 2020.
2. Kang WD, Choi, HS, Kim, SM, et al. Is vaccination with quadrivalent HPV vaccine after loop electrosurgical excision procedure effective in preventing recurrence in patients with high-grade cervical intraepithelial neoplasia (CIN2–3)?. Gynecol Oncol. 2013;130(2):264-268. doi:10.1016/j.ygyno.2013.04.050. Accessed 8 January 2021.
3. Ghelardi A, Parazzini F, Martella F, et al. SPERANZA project: HPV vaccination after treatment for CIN2+. Gynecol Oncol. 2018; 2018 Nov;151(2):229-234. doi: 10.1016/j.ygyno.2018.08.033. Accessed 8 January 2021.
4. Petrillo M, Dessole M, Tinacci E, et al. Efficacy of HPV vaccination in women receiving LEEP for cervical dysplasia: a single institution’s experience. Vaccines 2020 Jan 25;8(1):45. doi: 10.3390/vaccines8010045.
5. Sand FL. Kjaer SK, Frederiksen K, Dehlendorff C. Risk of cervical intraepithelial neoplasia grade 2 or worse after conization in relation to HPV vaccination status. Int. J. Cancer 2020 Aug 1;147(3):641-647. doi: 10.1002/ijc.32752.
6. Paavonen J, Naud P, Salmerón J, et al. Efficacy of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine against cervical infection and precancer caused by oncogenic HPV types (PATRICIA): final analysis of a double-blind, randomised study in young women. [published correction appears in Lancet. 2010 Sep 25;376(9746):1054]. Lancet 2009;374(9686):301-314. doi:10.1016/S0140-6736(09)61248-4.
7. Del Pino M, Martí C, Torras I, et al. HPV vaccination as adjuvant to conization in women with cervical intraepithelial neoplasia: a study under real-life conditions. Vaccines 2020 May 23;8(2):245. doi: 10.3390/vaccines8020245.