HPV Vaccination: Preventing Cervical Cancer (II)

Introduction

Firstly, some information about cervix and cervical cancer.

Cervix is the lower end of the uterus, about 2.5 to 3.5 cm long on top of the vagina

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Cervix

Cervical cancer is cancerous/ malignant growth or tumor resulting from the uncontrolled division of abnormal cells at the cervix. 

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Fungating cervical tumor

Many are detected via Pap smear during screening, as patients are asymptomatic during early stages. Other presentations are abnormal vaginal bleeding (usually postcoital), vaginal discomfort, malodorous discharge, and dysuria.

  • Pap testing recommendation is once every 3 years for all females aged 20–65 years.
  • According to the World Health Organization (WHO) Health Surveys 2001/2002, Pap smear coverage was only low 23%.

Cervical cancer’s disease burden in Malaysia and distribution of cervical cancer according to stages:

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Cervical cancer is the ten most common cancers in Malaysia (Malaysia National Cancer Registry Report 2007-2011).
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Cervical cancer: Distribution of cervical cancer according to stage in Malaysia compared to developed country (Malaysia National Cancer Registry Report 2007-2011).

Human Papillomavirus (HPV) and Cervical Cancer

HPV is double-stranded DNA virus which infects human epithelial cells (skin, anogenital mucosa, oropharyngeal mucosa). There are more than 200 different strains of the virus (15-20 oncogenic, 30-40 anogenital).

HPV is transmitted via vaginal, anal, or oral sex with someone who has the virus, even when an infected person has no signs or symptoms as most infected individuals are unaware that they are infected. Non-sexual contact (direct skin to skin contact).

Who is at risk of HPV infection?

  • Young age (peak age group 20-24 years old)
  • Lifetime high number of sex partners
  • Early age of first sexual intercourse
  • Smoking (decreases immunity)
  • Oral contraception use (sexual behaviour)
  • Women who have been diagnosed with a sexually transmitted disease.

Recognised as as the underlying cause of cervical cancer. The most important cause of cervical cancer is persistent HPV infection. (WHO, NIH 1996).

Screen Shot 2017-07-07 at 12.04.57 AM.png
Progression from pre-cancerous/ malignant to invasive cancer.

The human papillomavirus (HPV) is detected in 99% of cervical cancer, in particular the oncogenic subtypes such as HPV 16 and 18 (causing about 70% of cervical cancers worldwide).

hpvdiagram-afp.jpg
Persistent infections with high-risk HPVs (16, 18) leading to dysplasia, then carcinoma-in-situ (CIS) and finally to invasive squamous cell carcinoma (AFP image)

Other cancers caused by HPV: anal (89%-93%), oropharynx (70%), vaginal (60%-65%), vulva (20%-50%), penile (5%) (E Barr, 2008).

HPV Vaccination

HPV vaccine induce antibody response but not the disease. It’s able to produce higher levels of neutralizing antibody than natural infection and offer protection at least 10 years (ongoing studies).

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Survey done to identify reasons for parents not vaccinating their children.

HPV vaccine most effective and ideally to be given before 1st sexual contact.

  • Not sexually active? One study examined the detection of HPV in vagina before first vaginal intercourse. HPV was detected in 46% of women prior to first vaginal sex. Seventy percent of these women reported non-coital behaviors that may explain modes of acquiring the HPV infection (Shew, 2013)

Vaccine will NOT have any therapeutic effect/ eliminate EXISTING HPV infection but can provide protection against infection of different HPV strains that are not infected yet.

Three types of HPV vaccine in the market now:

  • GARDASIL 9-valent HPV Vaccine which protects against HPV types 6, 11, 16, 18, 31, 33, 45, 52, 58.
  • GARDASIL Quadrivalent HPV Vaccine which protects against HPV types 6, 11, 16, 18.
  • CERVARIX Bivalent HPV Vaccine which protects against HPV 16, 18 only – currently used in Malaysia National Immunisation Program (NIP)

Recommended HPV vaccination schedule:

  • 3 doses (0-, 2-, 6-month dosing regimen) for 15-26 years/ those who are immunocompromised
  • Two doses acceptable for 9-14 years

Common side effects of HPV vaccination are pain, redness, or swelling in the arm where the shot was given, nausea, muscle ache, headache, fever.

What’s Happening In Malaysia?

By end of 2011, 40 countries around the world had introduced HPV vaccine in their national immunization schedule.

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Projected reduction of cervical cancer incidence more than 50% (Aljunid, 2007)

In Malaysia, National Immunisation Program (NIP) started routine HPV vaccination in 2010 only for girls age 13 years, involving around 230k Form 1 students yearly.

  • Achievement: full course HPV vaccination (two doses; second dose is given 6 months after first dose) coverage of 87% in 2011 and 95% in 2016.
  • Good job!

There is still room for improvement.

I’m actually disappointed with the current use of Cervarix bivalent vaccine for HPV vaccination, which cover only two main oncogenic HPV strain (16, 18).

Initially, when HPV vaccination was started in 2010, if I’m not mistaken, Gardasil quadrivalent was used but it was somehow ‘downgraded’ to Cervarix bivalent vaccine.

The reasons given were that price was cheaper and the additional protection against HPV type 6 and 11 is merely to prevent genital warts, not cervical cancer.

However, by late 2014, Gardasil-9 valent obtained approval by FDA. Gardasil-9 valent offers protections against HPV types 6, 11, 16, 18, 31, 33, 45, 52, 58.

This time, those extra protection are against oncogenic strain that commonly cause cervical cancer in Malaysia (see below) but our children are still stuck with Cervarix bivalent vaccination.

Screen Shot 2017-07-08 at 10.22.20 PM.png
The most frequent HPV oncogenic types causing cervical cancer in Malaysia. An individual can be infected with more than one oncogenic/ high grade strain of HPV (Bruni L, 2017)

Finally

Our country need to be more current and quickly adapt and adopt best practices because whatever we decide today for our children with regards to HPV vaccination, the outcome (reduction in cervical cancer incidences) will be seen in the next 20 – 40 years later.

If you see what I saw today in my clinic, a young patient in her early 40s, diagnosed with cervical cancer, you’ll be wondering why HPV vaccination wasn’t available sooner to prevent this dreaded disease from happening.

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