Key messages

• Human papillomavirus (HPV) vaccination in comparison to no HPV vaccination in women with conisation (removal of a cone of tissue that contains abnormal cells, also known as cone biopsy) may reduce the risk of precancerous cervical cell changes (primarily CIN 2+).

• Due to limitations in data, we are not sure whether HPV vaccination (given shortly before, at, or after conisation) in comparison to no HPV vaccination in women with conisation affects cervical cancer risk or persistent HPV infection.

• Further high-quality studies are needed to assess the effectiveness and unwanted effects of HPV vaccination in women with conisation. These trials should also consider specific groups, such as women who had received HPV vaccination before and different age groups.

What is human papillomavirus and how is it treated?

Cervical cancer (cancer in the neck of the womb) is the fourth most common cancer affecting women worldwide. It is caused by persistent infection with specific types of human papillomavirus (HPV). While HPV infections are common and usually resolve without any problems, persistent HPV infections can progress to abnormal cell changes in the cervix (that is, precancerous conditions), called cervical intraepithelial neoplasia (CIN). These precancerous conditions can be classified as low-grade lesions (called CIN 1) and high-grade lesions (called CIN 2 and CIN 3). While low-grade lesions usually reduce spontaneously without treatment, high-grade lesions have a higher chance of progressing to cervical cancer. CIN 3 corresponds to carcinoma in situ (abnormal cells confined to where they first occurred), and adenocarcinoma in situ (abnormal cells that have moved to glands); it is well accepted that these immediately precede cervical cancer.

There are more than 200 types of HPV, and over 40 of them infect the genital area. Seven in 10 cervical cancers are caused by HPV types 16 and 18. Women diagnosed with CIN 2 and CIN 3 are usually considered for cervical conisation (also known as cone biopsy), a surgical procedure to remove abnormal cells to prevent progression to cervical cancer.

In Europe, there are three approved HPV vaccines: a bivalent (which protects against two HPV types), quadrivalent (which protects against four HPV types), and nonavalent (which protects against nine HPV types) vaccine. HPV vaccination is used to prevent cervical cancer, but its effectiveness for women with conisation remains uncertain. Of note, we use the term 'with conisation' interchangeably to refer to whenever the HPV vaccination was given around the time of the conisation procedure, that is, before, at, or, after the procedure.

What did we want to find out?

We wanted to find out how effective HPV vaccination is for women who had or undergo conisation to remove precancerous cervical lesions, and if it has any unwanted effects.

What did we do?

We searched for studies that examined the effects of HPV vaccination in women of any age with conisation to treat precancerous cervical cell changes caused by HPV. We summarised the results, assessed their reliability, and rated our confidence in the evidence.

What did we find?

We found 13 studies that included 21,453 women with conisation. The studies varied in design and quality. Most studies were conducted in Europe (10 studies) and used the quadrivalent (seven studies) or nonavalent (one study) HPV vaccine. Some studies monitored women for more than 60 months.

Main results

• HPV vaccination in comparison to no HPV vaccination in women with conisation may reduce the risk of precancerous lesions. However, results have to be interpreted with caution.

• We are not sure whether HPV vaccination in comparison to no HPV vaccination in women with conisation has an effect on cervical cancer and persistent HPV infection.

• There were no data for new HPV infections, adenocarcinoma in situ, and quality of life, and the remaining evidence was mostly inconclusive.

• Unwanted effects included minor reactions (redness and rash: 92 in every 100 women; headache: 8 in every 100 women) and severe allergies (1 in every 100 women).

What are the limitations of the evidence?

The evidence was mainly from studies that had potential problems with how they were conducted. Only two studies were designed to produce more robust evidence. The studies did not provide enough information to know whether a previous HPV vaccination means that another vaccination and its timing in relation to the conisation procedure gives different results. We also need to know more about the effects on different age groups.

How up to date is this evidence?

The evidence is current to May 2023.