Reports

This report is based on medical evidence presented at sanctioned medical congress, from peer reviewed literature or opinion provided by a qualified healthcare practitioner. The consumption of the information contained within this report is intended for qualified Canadian healthcare practitioners only.

Based on the Protocole d’immunisation du Québec Update published on-line June 2007

Human papillomavirus (HPV) is the most common cause of sexually transmitted infections in Canada, primarily affecting individuals aged 15 to 29 years. Most HPV infections clear spontaneously without clinical manifestations. The invisibility of acute infection contributes to viral transmission and spread, which occurs via contact with skin or mucous membranes. However, the virus can have potentially serious outcomes. Of the dozens of viral subtypes, types 6 and 11 are recognized as the principal cause of anogenital warts (condylomata). These lesions, while treatable, can constitute a substantial health, social and psychological burden. More serious is the etiologic connection between types 16 and 18—which are the most common types of HPV in North America—and cancer of the cervix. The virus has also been associated with cancers of the vulva, vagina, penis and anus. HPV 16 and 18 account for about three out of four cervical and other anogenital tumours.

The Vaccine

The new quadrivalent vaccine against HPV has 95% to 100% efficacy in the prevention of HPV infection caused by types 6, 11, 16 and 18. It is currently indicated in girls and young women between the ages of nine and 26 years. Ideally, the vaccine should be administered before the patient becomes sexually active. However, it is also effective later and/or when given after a first HPV infection has occurred, as the immunity conferred by an infection is confined to the viral type. Studies are underway to determine if vaccination should also be advised for older women and men.

Three 0.5-mL doses are required; the second and third doses are given two and six months after the first dose. Some flexibility in this timing is allowable (e.g. the second dose can be given at least one month after the first and the third at least three months later). For greatest efficacy, patients should be encouraged to adhere to the recommended schedule.

Each dose of the vaccine comes in a separate vial or pre-filled syringe. The health care professional administering the vaccine should shake the vial before the liquid is aspirated into the syringe; alternatively, the syringe itself can be shaken. After agitation, the liquid has a cloudy white appearance. The vaccine is administered in the deltoid muscle or the high anterolateral area of the thigh.

After the full three-dose course of vaccination, nearly all healthy, HPV-seronegative patients will achieve antibody titres 10 to 100 times higher than those experienced after HPV infection. Higher titres are observed in younger patients. The rate of prevention of genital warts is 99%.

Double-blind, placebo-controlled studies were conducted in women aged 16 to 26 years with no history of infection with the four HPV types included in the vaccine. Their data show that over five years, the vaccine was 100% effective at preventing cervical intraepithelial neoplasia (grade 2 or 3) and adenocarcinoma in situ (the precursor to cervical cancer) related to HPV types 16 and 18. Studies also demonstrate the vaccine has 100% efficacy in the prevention of vaginal and vulvar intraepithelial neoplasia caused by any of the four HPV subtypes. The vaccine’s efficacy over a period longer than five years is not yet known.

As with most vaccines, the majority of side effects observed are benign and transient. About three out of four patients report an injection site reaction (redness, sensitivity, swelling), which can be alleviated with a cold compress. In clinical studies, systemic reactions such as fever, nausea, dizziness and diarrhea were equally frequent in patients receiving vaccine or placebo. (Patients who experience fever can be advised to rest, drink fluids and take acetaminophen.) Headache or malaise may also be reported. Less than 0.1% of patients have experienced more severe reactions (e.g. bronchospasm, gastroenteritis, pain and limitation of movement at the injection site). In these instances, no causal relationship to the vaccine was established.

Additional Advice and Precautions

Women who are already sexually active may already have been exposed to HPV. Although sexual activity and prior infection are not contraindications, such patients should be advised that they may already have been infected and that if so, the vaccine is not a treatment. Adverse reactions to the vaccine are not more severe in women who have previous HPV infection.

Response to the vaccine may be suboptimal in those who are immunosuppressed. The vaccination should not be administered to patients who have moderate to severe acute illness, whether or not they have fever. The vaccine is not advised for pregnant women, although clinical studies suggest there is no danger for the fetus. Allergy to any component of the vaccine (L1 proteins from the four virus subtypes, aluminum hydroxyphosphate sulfate, polysorbate, sodium borate, sodium chloride, histidine) is also a contraindication. The vaccine’s single-dose vial contains no natural latex or preservative. The product must be refrigerated (2-8º C) and be protected from long exposure to light.

The complete PIQ is available at http://publications.msss.gouv.qc.ca/acrobat/f/documentation/piq/mise_jour/juin_07.pdf. Pages 342I to 342N of the PIQ specifically address the HPV vaccine. The document also contains a patient information handout (new page 27B).

Questions and Answers About the HPV Vaccine

The following question-and-answer session was conducted during interviews with Dr. Marc Steben, medical consultant, Directorate of Biological, Environmental and Occupational Risks, Institut national de santé publique du Québec, and with Ms. Nicole Héon-Lepage, RN, owner of Concept Santé PLM clinic, Montreal.

Q: What is the role of frontline health professionals in introducing the HPV vaccine?

Dr. Steben: It’s a physician’s obligation. When a vaccine becomes a clinical standard, physicians must abide by the new standard. Also, considering the recommendations from NACI, physicians cannot choose not to talk about the vaccine.

Ms. Héon-Lepage: First and foremost, they have to make patients aware of HPV because many women have never heard about it. The issue could be broached at the time of an annual check-up or gynecological exam.

Q: Do you recommend the HPV vaccine to all patients in the targeted age group?

Dr. Steben: The vaccine is recommended for all girls and women aged 9 to 26 years, which is a fairly large range. It is more effective if administered before a girl becomes sexually active because she has not yet been exposed to HPV, and it is well known that the virus is acquired very early. However, there is evidence showing that girls who have been exposed to the virus and who have developed HPV disease, e.g. warts, abnormal Pap tests or vulvar or vaginal lesions, still benefit from its use. In women older than 26, its effectiveness is now being reviewed, so it remains a personal decision to be made through consultation with the physician.

Q: Have you experienced or do you anticipate difficulties in discussing the subject with patients or their parents?

Dr. Steben: This gives parents another opportunity to establish a dialogue with their kids on sexuality, pregnancy and sexually-transmitted diseases [STDs]. Many women have sisters, mothers, grandmothers or aunts who have had cancer or abnormal cells, or warts, so this is a different way of addressing the issue.

Ms. Héon-Lepage: Depending on the age of the girl, parents may be reluctant or surprised. Once they have been made aware, they are more receptive, but we do have to explain it in very simple terms.

Q: What if parents think the vaccine is unnecessary or that their daughter may still be too young for it?

Dr. Steben: All parents wish to become grandparents, so if we want our children to become parents, they first have to be sexually active! It is known that HPV infection is highly democratic. With an average of two partners, more than 25% of girls will acquire at least one type of HPV. If a parent does not understand that, he or she shows little consideration for his or her child’s health.

Ms. Héon-Lepage: I always say, “When you fooled around, did you tell your parents?” Everyone chuckles. I then go on to explain that this STD can be acquired without penetration and cannot be prevented with condoms. It can be transmitted by simple touch, which is a very frequent method of transmission. The first person I vaccinated was my 18-year-old daughter.

Q: Do you anticipate challenges with the three-dose schedule?

Dr. Steben: It goes without saying that a single-dose protocol would be better. However, parents are used to such schedules because childhood vaccines and some travel vaccines require three doses. Once a girl has had all three doses, she is probably protected for life.

Ms. Héon-Lepage: Maybe financially, but the HPV vaccine is already covered by some group insurance policies. Depending on her age, the patient may not like the three-dose schedule. The vaccination does cause discomfort, i.e. it pinches the skin. We therefore have to explain that three doses are required for protection. Once we explain how vaccines work, there is no problem.

Q: What impact do you think widespread use of the vaccine will have?

Dr. Steben: The impact on public health could be huge. It is known that HPV infection is a common reason for seeing a physician. It is also a question of quality of life for women. If a woman is diagnosed with a wart and the treatment ends up destroying her vulva, vagina or cervix, she will have physical and psychological scars. And the reduced incidence of cervical cancer and HPV disease will translate into savings that can be allocated to other programs or improved screening of cervical cancer.