Human papillomaviruses (HPV) are a group of over 100 types of viruses. Over 30 HPV are sexually transmitted. HPV is the major cause of cervical cancer, the 5 th most common cancer in women in Singapore. HPV also plays a role in other genital cancers, both in women and in men.
HPV infections are extremely common; over 20 million people are affected worldwide. More than 50% of sexually active men and women acquire genital HPV infection at some point in their lives. The age specific annual incidence of HPV infection is seen in Table 1.
Age |
Incidence |
15-16 |
0.1 |
17 |
0.12 |
18-20 |
0.15-0.17 |
21-23 |
0.10-0.12 |
24-29 |
0.05 |
30-49 |
0.01 |
50+ |
0.005 |
(Table 1)
HPV binds and infects keratinocytes in the basal cells of the cervical epithelial layer (integrins are receptors).
Microtrauma facilitates the viral access to the basal cells. The majority of infected women have transient infections but HPV DNA can persist in the cervical tissue for 6-12 months (HPV 16 and 18 for the longest).
Capsid proteins L1 and L2 present in HPV particle shell, and interact with human epithelial cells during early stages of infection prior to the entry of viral DNA. These are therefore ideal targets for prophylactic vaccines.
E1 and E2 are replication proteins required for HPV replication. They are continually expressed in later stages of disease binding to p53 and pRB, thereby exerting their role in tumorigenesis. These are ideal targets for therapeutic vaccines.
Successful protection against HPV 16 and 18 can prevent 70% of cervical cancers, and successful protection against 8 types of HPV (multivalent vaccines) may protect against 95% of all cervical cancers. Prophylactic vaccines- induce virus neutralizing antibodies to protect against new infections, while therapeutic vaccines- induce cellular immunity against infected cells.
Two very large randomized studies have now been completed using prophylactic vaccines against HPV infection. The first was published in 2002 in the New England Journal Of Medicine (2002: 347(21): 1645-51 ). The second in 2004 in The Lancet (2004: 364:1757). Both these studies compared the use of prophylactic vaccines versus a placebo in the prevention of cervical intra-epithelial neoplasia (CIN).
Both these studies have shown a statistically significant ability to prevent persistent HPV infection and lower the incidence of ASCUS (Atypical Squamous Cells of Undetermined Significance), SILs (Squamous Intraepithelial lesion) and CIN (Carcinoma In Situ) caused by HPV for which the vaccines was specific. Both studies showed that these vaccines failed to protect against CIN caused by other HPVs.
While the efforts of preventing HPV infection with vaccine can be lauded, the following issues have not been resolved: Vaccines are specific and do not prevent all HPV infection. What is the longevity of these vaccines? Will boosters be required? These vaccines do not prevent other sexually transmitted diseases (like HIV). What is the scale (therefore cost) of vaccination compared to cervical screening?
Many more studies need to be performed, not just to find a vaccine stable enough to protect against more than two three HPV infections, but also the economic benefits of using such vaccines. We continue to hold our breaths.
See Hui Ti
Associate Consultant
Department of Medical Oncology
National Cancer Centre, Singapore
