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Should patients undergoing surgical treatment for cervical lesions also receive an HPV vaccination?


Human papillomavirus (HPV) vaccine given around the time women have surgery for precancerous cervical lesions might lead to a reduction in the risk of lesions returning, as well as other HPV-related diseases, but the effects of this remain unclear.

The authors of the new study, published in The BMJ, explained that women who have been treated for high-grade cervical intra-epithelial neoplasia (CIN) have a “lifelong residual high risk of cervical cancer and other malignancies related to HPV infection,” and some research suggests that giving a preventive HPV vaccine alongside treatment for CIN might help to “reduce the risk in these women.”

HPV vaccination is highly effective at preventing the development of precancerous cervical lesions, CIN, and in the U.K., HPV vaccination is offered to girls and boys around the age of 12 or 13.

Eluned Hughes, head of information and engagement at Jo’s Cervical Cancer Trust, said: “Recent evidence has found that cases of cervical cancer have fallen 87% since the introduction of the HPV vaccine program in U.K. schools in 2008.”

“However, women over the age of 27, for whom the vaccine was not available, remain at increased risk of cervical cancer,” she highlighted.

Significant risk of bias and scarcity of data

In the study, researchers set out to explore the efficacy of HPV vaccination on the risk of HPV infection and recurrent diseases related to HPV infection in individuals undergoing local surgical treatment of preinvasive genital disease.

The systematic review and meta-analysis, led by researchers at Imperial College London, screened data from PubMed (Medline), Scopus, Cochrane, Web of Science, and from inception to March 31, 2021.

The researchers analyzed the results of 18 studies – two randomized controlled trials (RCTs), 12 observational studies, and four post-hoc analyses of RCTs.

The authors said that the two RCTs were classified as low risk of bias, while in the observational studies and post-hoc analyses, risk of bias was moderate for seven, serious for seven, and critical for two. Average length of follow-up was 36 months.

There was a reduction of 57% in the risk of recurrence of high-grade pre-invasive disease (CIN2+) in individuals who were vaccinated, compared with those who were not vaccinated. “The effect estimate was “even more pronounced” – a relative 74% reduction – when the risk of recurrence of CIN2+ was assessed for disease related to the two high-risk HPV types – HPV16 and HPV18,” explained the authors.

However, the researchers noted that these effects are unclear because of the “scarcity of data” and the “moderate to high overall risk of bias” of the available studies.

Quality of evidence inconclusive – more trials needed

With regards to CIN3, the risk of recurrence of was also reduced in patients who were vaccinated, but there was a high level of uncertainty about the quality of this evidence, cautioned the authors.

Evidence was also lacking on the benefit of HPV vaccination for recurrence of vulvar, vaginal, and anal lesions, as well as genital warts.

Analysis of the post-hoc studies from randomized controlled trial data with historic vaccination at randomization before the development of the disease reported inconsistent results, the authors said.

Several study limitations were acknowledged by the authors, including that most of the studies were observational, of low to moderate quality, and with relatively short follow-up times, which they pointed out prevented assessment of long-term effects. In addition, the average age of participants was not provided in most studies, and factors such as smoking – associated with a higher risk of recurrence – were not controlled for in many studies.

“HPV vaccination might reduce the risk of recurrence of CIN, in particular when related to HPV16 or HPV18, in women treated with local excision,” they concluded. However, they cautioned that “quality of evidence indicated that the data were inconclusive.”

“Large, appropriately powered, randomized controlled trials are required to establish the effectiveness of adjuvant HPV vaccination at the time of local surgical treatment of CIN,” they recommended.

“Given that the incidence of recurrence of high-grade disease is low in quality assured national screening programs, such as in the United Kingdom, absolute risks and a cost effectiveness analysis would be important in determining the implementation strategy of HPV vaccination after treatment,” the authors said.

Ms. Hughes said that the charity was pleased to see emerging research into the value of using the HPV vaccine to prevent the recurrence of cervical cell changes. She said that the charity looks forward to seeing “further large-scale studies into the effectiveness of this method.”

In the meantime, the charity encourages all women and other people with a cervix to attend their cervical screening and for young people to have the HPV vaccination when invited, as “these are the best tools we currently have to prevent cervical cancer,” she said.

A version of this article first appeared on Medscape UK.

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