HPV vaccination for the prevention of cervical precancer

This fact box will help you to weigh the benefits and harms of HPV-vaccination for the prevention of cell changes and cervical precancer. The information and numbers in this fact box represent no final evaluation. They are based on the best scientific evidence currently available.

This fact box was developed by the Harding Center for Risk Literacy.

What is cervical cancer?

Cervical cancer refers to an accumulation of abnormally altered cells in the lower part of the uterus whichdivide uncontrollably,also known as tumors.They usually develop near the cervix, which is the small opening in the narrow lower part of the uterus (cervix) that extends into the vagina [2].

In 2014, about 4,500 women in Germany developed cervical cancer. Every year about 1,500 women die from this type of cancer. The highest morbidity rates are currently found in women aged 35 to under 60 [3].

In many cases,the disease is caused by long-standing virus infections, which are also known as human papillomaviruses (HPV). They attack skin and mucous membrane cells, and are transmitted through sexual intercourse or intimate skin contact. Infections through body fluids such as sperm, blood or saliva are considered unlikely. It is estimated that about 90% of sexually active girls and women become infected with these viruses at some point in their lives, many between the ages of 20 and 30. Men can also contract and transmit HPV [2].

There are more than 200 different types of HPV. About 40 HPV types can cause infections in skin and mucous membrane cells [2]. Infection with the low-risk types HPV-6 and HPV-11 can, for example, cause benign skin growths (genital warts) in the vagina, on the labia, in the perineum or anal area, or on the penis and scrotum of men. HPV-16 and HPV-18 are so-called high-risk types, which are discovered in about 7 out of 10 women with cervical cancer [5].

Infection with virus types HPV-16 and HPV-18 usually goes unnoticed. Temporary tissue changes (dysplasia) can occur in the mucous membrane of the cervix. These often disappear on their own. Sometimes, however, certain HPV types settle in the mucous membrane for several years or decades. Then a cell change, and eventually cervical cancer, might slowly develop [2].

The cell changes can be classified according to certain criteria, which can be determined after a tissue sample (biopsy). The CIN level (cervical intraepithelial neoplasia) indicates the extent to which the cell changes have progressed. CIN1 is a mild form of cell change. CIN2 a moderate form of cell change. In CIN 3, the cell change is so advanced that the change can be described as a transition to cancer (precancerous stage). At this stage, the tumoris still restricted to the upper tissue layers, which is also called carcinoma in situ (CIS) and is still considered an early stage [4].   

If the tumor has already spread beyond the upper cell layer of the mucous membrane into the surrounding tissue, this is referred to as invasive cervical cancer [2].

Cervical cancer can also develop from altered gland cells. These cell changes are called adenocarcinoma. The preliminary stage of adenocarcinoma is referred to asadenocarcinoma in situ (AIS).

What is a HPV vaccination? 

The HPV vaccinationis designed to prevent the development of HPV infections, which can lead to various diseases such as genital wartsand cervical cancer.

The vaccine does not cause infections. It leads to an immune response, through which protective antibodies are produced. The vaccination usually requires two injections with a five-month interval in betweenthem. Two vaccines, Cervarix® and Gardasil 9®, have been on the German market since August 2017. Cervarix® works exclusively against HPV-16 and -18, while Gardasil 9® protects against a total of 9 HP viruses (HPV-6, -11, -16, -18, -31, -33, -45, -52, -58).

Who might consider a HPV-vaccination?

The Standing Vaccination Commission (STIKO) recommends to primarily vaccinate girls aged 9 to 14 against HPV. Up to the age of 17, the costs of a missed vaccination are also covered by the statutory health insurance [3].

The vaccination is not effective against already existing HPV infections. Therefore, the best point in time to complete the vaccination is before the first sexual intercourse [2].

The HPV vaccination can also protect boys and men from HPV infections. STIKO recommends vaccinating boys between the ages of 9 and 14 [6].

What are alternative options for prevention?

If someonewanted to protect oneself from an infection, he or she would have to live a completely abstinent life,or have a partner who has no other intimate contacts. Condoms can effectively protect against many sexually transmitted diseases, but not reliably against HPV, because they do not cover all skin areas in the genital area that could be affected [2]. 

Most HPV infections heal themselves as the immune system eliminates the HP viruses. If this does not succeed, the HPV infection will continue for a longer period of time. So far, there is no treatment that can target HPV directly.The statutory early detection programme offers women aged 20 and over the possibility of an annual cell smear from the cervix (PAP smear). Starting at the age of 35, an HPV test can be combined with the PAP smear every three years as part of the screening program [3].

Early detection

The statutory early detection programme offers women aged 20 and over the possibility of an annual cell smear from the cervix (PAP smear). Starting at the age of 35, an HPV test can be combined with the PAP smear every three years as part of the screening program [3].

Fact box on HPV vaccination for the prevention of cervical precancer
Fact box on HPV vaccination for the prevention of cervical precancer © Harding Center for Risk Literacy
What does the fact box show?

The fact box compares the benefits and harms of the HPV vaccination with a placebo vaccination.

The table may be read as follows:

About 164 out of every10,000 girls and women with a placebo injection developeda moderateform of cell change (CIN2) within 44 months. In comparison, 2 out of every 10,000girls and women with an HPV-vaccination developeda CIN2 within 44 months.

The numbers in the fact box are rounded. They are based on 26 studies with about 73,400 participants [1].

What other aspects should be considered?

The protection achieved by a vaccination against a HPV infection decreases with an increasingnumber of sexual partners [1].

In Germany, Gardasil® was replaced in 2017 by the ninefold vaccine Gardasil 9®, which was approved in 2014. The Robert Koch Institute classifies the new vaccine as safe as the previous one [6] and thus draws the same conclusions as international surveys [7]. So far, however, there are no studies comparing Cervarix® and Gardasil 9® with a placebo vaccination.

Do the results provide proof (evidence) for the benefits and harms of the HPV-vaccination?

The evidence is of overall moderate to high quality: 

Further research might change the results regarding the precancerous stage of adenocarcinoma (AIS) and side effects at the injection site (moderate quality ofevidence). A change in the findingsby further research regarding the precancerous stages CIN2 and CIN3, and the serious side effects (severe infections, inflammation and other non-lethal complications) is unlikely(high quality of evidence).

Version history of the fact box
  • October 2019 (update of the accompanying text, update of the evidence)
  • January 2016 (update of the evidence)
  • August 2015 (development)
Sources

Information for the fact boxes were obtained from the following sources:

[1] Arbyn M, Xu L, Simoens C, et al. Prophylactic vaccination against human papillomaviruses to prevent cervical cancer and its precursors. Cochrane Database of Systematic Reviews 2018(5).doi:10.1002/14651858.CD009069.

[2] IQWiG. Gebärmutterhalskrebs 2018. Available at: https://www.gesundheitsinformation.de/gebaermutterhalskrebs.2109.de.html (31.05.2019).

[3] Robert-Koch-Institut. Krebs in Deutschland 2013/2014. 2017. Available at: https://www.krebsdaten.de/Krebs/DE/Content/Publikationen/Krebs_in_Deutschland/kid_2017/krebs_in_deutschland_2017.pdf  (31.05.2019).

[4] Deutsches Krebsforschungszentrum. Vorstufen des Gebärmutterhalskrebs 2018. Available at: https://www.krebsinformationsdienst.de/tumorarten/gebaermutterhalskrebs/vorstufen.php (31.05.2019).

[5] Krebsinformationsdienst, Deutsches Krebsforschungszentrum 2018. Available at: www.krebsinformationsdienst.de/vorbeugung/risiken/hpv2.php (11.09.2019).

[6] Robert-Koch-Institut. Wissenschaftliche Begründung für die Empfehlung der HPV-Impfung für Jungen im Alter von 9 bis 14 Jahren, 2018. Epidemiologisches Bulletin Nr. 26.Berlin.

[7] Signorelli C, Odone A, Ciorba V,et al. Human papillomavirus 9-valent vaccine for cancer prevention: a systematic review of the available evidence. Epidemiol Infect. 2017, Jul; 145(10): 1962–1982. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5974698/

Documentation on how the numbers in the fact box were determined is available on request.