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Meta-analysis finds HPV can help prevent return of cervical cancer

The human papillomavirus (HPV) vaccine, when administered to women when pre-cancerous lesions are removed from their cervix, might slash the risk of cells recurring and them getting cervical cancer, a study has found.

But the findings also suggest the vaccine may have a second key role in thwarting cervical cancer. British researchers believe that administering a dose of it to women around the time they have surgery to remove pre-cancerous cells prevent them from coming back, reports The Guardian.

HPV is a term for a group of very common viruses affecting the skin. There are more than 100 types of HPV and, in most people, HPV does not carry any symptoms. However, some types are high risk and can cause changes to cells that can sometimes turn in to cancer. In particular, HPV-16 and HPV-18 strains are largely responsible for women developing cervical cancer.

Cases of cervical cancer in the UK have fallen hugely since school pupils aged 13 and 14 – first girls and later boys – began being offered HPV jabs in 2008 as protection against the disease.

“HPV vaccination is highly effective at preventing the development of pre-cancerous cervical lesions (cervical intraepithelial neoplasia or CIN),” according to the findings, which have been published in The British Medical Journal.

CIN means that abnormal changes of cells that line the cervix have been detected. If left untreated they can develop into cervical cancer. There are three forms of CIN, known as CIN1, 2 and 3.

The study team, led by Maria Kyrgiou of Imperial College London, analysed 18 previous papers on the subject and found people who had been vaccinated against HPV had a 57% lower risk of high-grade pre-invasive disease (CIN2+) recurring than those who had not had the jab.

The risk was reduced by even more – 74% – when the chances of CIN2+ recurring were assessed for HPV16 and HPV18, the two types of the virus that cause many cases of cervical cancer.

However, the authors stressed that the evidence for those reductions was “inconclusive” and that large-scale randomised control trials were needed to confirm that vaccination conferred that benefit.

While HPV jabs had cut cases of cervical cancer by 87% since 2008, women over 27, who could not get it, are still at increased risk of developing the disease.

Alice Davies, a health information manager at Cancer Research UK, was cautious about the findings. “This study looked at whether the HPV vaccine can stop further cell changes happening after people have had treatment to remove abnormal cells caused by HPV infection. But it’s still too early to say if using the vaccine in this way is beneficial, and larger high-quality studies and trials are needed.”

Study details

Role of human papillomavirus (HPV) vaccination on HPV infection and recurrence of HPV related disease after local surgical treatment: systematic review and meta-analysis

Konstantinos S Kechagias, Ilkka Kalliala, Sarah J Bowden, Antonios Athanasiou, Maria Paraskevaidi, Evangelos Paraskevaidis, Joakim Dillner, Pekka Nieminen, Bjorn Strander, Peter Sasieni, Areti Angeliki Veroniki, Maria Kyrgiou.

Published in The BMJ on 14 June 2022

Abstract

Objective
To explore the efficacy of human papillomavirus (HPV) vaccination on the risk of HPV infection and recurrent diseases related to HPV infection in individuals undergoing local surgical treatment.

Data sources
PubMed (Medline), Scopus, Cochrane, Web of Science, and ClinicalTrials.gov were screened from inception to 31 March 2021.

Review methods
Studies reporting on the risk of HPV infection and recurrence of disease related to HPV infection after local surgical treatment of preinvasive genital disease in individuals who were vaccinated were included. The primary outcome measure was risk of recurrence of cervical intraepithelial neoplasia grade 2 or higher (CIN2+) after local surgical treatment, with follow-up as reported by individual studies. Secondary outcome measures were risk of HPV infection or other lesions related to HPV infection. Independent and in duplicate data extraction and quality assessment were performed with ROBINS-I and RoB-2 tools for observational studies and randomised controlled trials, respectively. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) was implemented for the primary outcome. Observational studies and randomised controlled trials were analysed separately from post hoc analyses of randomised controlled trials. Pooled risk ratios and 95% confidence intervals were calculated with a random effects meta-analysis model. The restricted maximum likelihood was used as an estimator for heterogeneity, and the Hartung-Knapp-Sidik-Jonkman method was used to derive confidence intervals.

Results
22 articles met the inclusion criteria of the review; 18 of these studies also reported data from a non-vaccinated group and were included in the meta-analyses (12 observational studies, two randomised controlled trials, and four post hoc analyses of randomised controlled trials). The risk of recurrence of CIN2+ was reduced in individuals who were vaccinated compared with those who were not vaccinated (11 studies, 19 909 participants; risk ratio 0.43, 95% confidence interval 0.30 to 0.60; I2=58%, τ2=0.14, median follow-up 36 months, interquartile range 24-43.5). The effect estimate was even stronger when the risk of recurrence of CIN2+ was assessed for disease related to HPV subtypes HPV16 or HPV18 (six studies, 1879 participants; risk ratio 0.26, 95% confidence interval 0.16 to 0.43; I2=0%, τ2=0). Confidence in the meta-analysis for CIN2+ overall and CIN2+ related to HPV16 or HPV18, assessed by GRADE, ranged from very low to moderate, probably because of publication bias and inconsistency in the studies included in the meta-analysis. The risk of recurrence of CIN3 was also reduced in patients who were vaccinated but uncertainty was large (three studies, 17 757 participants; 0.28, 0.01 to 6.37; I2=71%, τ2=1.23). Evidence of benefit was lacking for recurrence of vulvar, vaginal, and anal intraepithelial neoplasia, genital warts, and persistent and incident HPV infections, although the number of studies and participants in each outcome was low.

Conclusion
HPV vaccination might reduce the risk of recurrence of CIN, in particular when related to HPV16 or HPV18, in women treated with local excision. GRADE assessment for the quality of evidence indicated that the data were inconclusive. Large scale, high quality randomised controlled trials are required to establish the level of effectiveness and cost of HPV vaccination in women undergoing treatment for diseases related to HPV infection.

 

The BMJ article – Role of human papillomavirus (HPV) vaccination on HPV infection and recurrence of HPV related disease after local surgical treatment: systematic review and meta-analysis (Open access)

 

The Guardian article – HPV vaccine after removal of precancerous cells may cut cervical cancer risk (Open access)

 

See more from MedicalBrief archives:

 

HPV vaccine cuts cervical cancer by nearly 90% — UK population registry study

 

HPV vaccine significantly lowers infection rates in teen girls – CDC study

 

HPV vaccine shows success in gay and bisexual men – HYPER2 study

 

Single HPV vaccine dose may be effective against cervical cancer

 

 

 

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