A8. The role of HPV in the pathomechanism of gynecologic malignancies; HPV vaccination

From greek.doctor

Human papillomavirus is a DNA virus which is closely related to cervical, vaginal, and vulvar cancer, as well as their precursors. It’s the most common sexually transmitted infection.

There are hundreds of serotypes of HPV, not all of which cause cancer. Those which do are called “high-risk”, which includes, 16, 18, 31, 33, 45, 52, and 58, which account for over 90% of cases, as well as other types. However, HPV 16 and 18 account for 2/3 of cases and are therefore the highest risk. (Types 6 and 11 are low-risk and rather cause genital warts).

HPV 16 and 18 also accounts 90% of anal cancers.

Risk factors for HPV infection

  • Young age
  • Multiple sex partners
  • Early sexual debut
  • Early childbearing
  • Multiparity

The peak age group of acquiring HPV infection is 20 – 24 years. The lifetime risk of a sexually active woman acquiring HPV infection is upwards of 80%.

Pathology

HPV expresses two oncoproteins, E6 and E7. E6 inhibits the tumor suppressor p53, and E7 inhibits the tumour suppressors retinoblastoma protein (pRb), p21, and p27.

HPV infection affects squamous cells and causes hyperplasia and hyperkeratosis. An atypical form of cells called the koilocyte is characteristic for HPV infection.

HPV vaccination

Three different vaccines against HPV exist:

  • Bivalent HPV vaccine (Cervarix)
    • Against types 16, 18
    • However, there is high cross-protection against other high-risk types
  • Quadrivalent HPV vaccine (Gardasil)
    • Against types 6, 11, 16, 18
  • 9-valent HPV vaccine (Gardasil 9)
    • Against types 6, 11, 16, 18 + 5 other high-risk types

These vaccines prevent the initial HPV infection and subsequent HPV-associated lesions. They are safe and effective measures of protecting against HPV-related cancers. However, they do not protect against all high-risk HPV types, and so screening for cervical cancer should still be performed. The vaccination is most effective when given before the HPV infection, and so it should be given before sexual debut.

Vaccination of males is important as well as it protects against male HPV-associated cancers like penile cancer, as well as contributing to “herd immunity” for females.

Indications

WHO recommends that the HPV-vaccine should be part of the childhood vaccination program of all countries. It is included in the childhood vaccination program in 82 countries.

In Hungary and Norway it’s offered to both males and females in 7th grade (12 – 13 years). Hungary only recently (fall 2020) began offering it to males. In Hungary the quadrivalent vaccine is used.