Can the HPV vaccine reduce the incidence of cervical cancer –
The preventable death?
Cervical cancer is the most easily detectable and preventable cancer in women, yet it is the 4th most common in incidence and cancer mortality worldwide. It is the most commonly diagnosed cancer in 28 countries and the leading cause of cancer death in 42 countries. Globally, around 13.1/100,000 women are diagnosed with cervical cancer each year. The most chilling truth is that in spite of the fact that its most preventable and easily detectable cancer, yet in India more than 200 women die every day, 8 women die every hour, and every 7 min a woman loses her life because of cervical cancer. Can we do something to prevent it?
Viral infections constitute 15-20% of all human cancers and a total of 98.7% of all cervical cancers are HPV positive. At 4 years after the first intercourse, more than 50% of the young population is inflicted with HPV and by age 50 yrs 80% of women would have contracted HPV infection. Young women <25 yrs are at greatest risk of HPV infection and 2nd peak occurs in age >55 yrs due to changes in immune function with menopause. Women infected with HIV have more than twice the risk of HPV infection as compared to non-HIV (64% vs 28%).
High-grade precancerous lesions are estimated to take 10 yrs to progress to cervical cancer. Routine screening with Pap smear can detect most of the cancers in the precancerous stage making it curable. 40-50% of cervical cancers are diagnosed in women who undergo routine cervical cytology. 4 out of 5 women are diagnosed with cancer who had not been tested with Pap smear in years.
Remember, HPV infection is the main cause of cervical cancer and it is preventable. It enters through cervical micro-abrasions during sexual intercourse and the majority are asymptomatic and 90% infections heal within 2 years but in 0.8% cases, high-risk HPV types persist, reach deeper layers, and can transform into cancer over a number of years. It takes about 7-10 years for 1st infection to transform to Cervical Intraepithelial Neoplasia (CIN 3) yrs & further 10 yrs for conversion to full-blown cervical cancer.
Human Papillomavirus is a double-stranded DNA of papillomaviridae family. More than 100 types of HPV infection have been identified, 40% colonize the genital tract and 15 types are found to be carcinogenic. High-risk HPV DNA is found to be present in 99.7% of cervical cancers. High-risk types are 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 68, and 59 and potential high-risk are types 53, 66, 70, 73, and 82. Out of these, HPV16 and 18 are the most virulent high-risk genotypes and cause about 70% of all invasive cancers. Cervical cancers caused by HPV16 and 18 appeared earlier than that caused by other types and HPV18 and 45 are implicated in more aggressive cervical adenocarcinomas. Types 6 and 11 are associated with 90% of anogenital warts.
HPV virus has promoter and enhancer elements, 6 early proteins, 3 regulatory proteins (E1, E2, and E4) and 3 oncoproteins (E5, E6, and E7) which lead to viral replication & cell transformation and 2 structural proteins L1 and L2 that compose the capsid of the virus. Because, we know the structure of the virus, so thankfully we have an HPV vaccine to prevent cervical cancer. The prophylactic vaccines have been made using HPV virus-like particles (VLP) to generate neutralizing antibodies against major capsid proteins L1 and L2. These also protect against anal, vulvar, vaginal cancers, anogenital warts, and vulvar, vaginal, cervical, and anal intraepithelial neoplasias. Therapeutic vaccines are in pipeline that can potentially eliminate pre-existing lesions and malignant tumors by generating cellular immunity against HPV infected cells that express early viral proteins as E6 and E7.
HPV vaccines are type-specific-meaning thereby that they are effective only against the type of HPV which is available in the vaccine. These are prophylactic vaccines and hence are effective before any sexual infection. They are not therapeutic and hence do not treat any existing infection. There are 4 types of HPV vaccine – Monovalent, Bivalent (Cervarix), Quadrivalent (Gardasil), and Nanovalent (Gardasil-9). The monovalent vaccine is against only HPV 16 and is in trial phases. Nonavalent is against 9 types of HPV and is available as Gardasil-9. It’s not yet available or approved in India. The details of each vaccine are summarised below in a table.
The ideal age for vaccinating young girls is at 11-12 years of age (on time) although vaccination can start at 9 years of age (early vaccination and we can start priming the parents at this time). If someone is not vaccinated till 11 or 12 years of age then catch up vaccination can be done until 26 yrs of age before any sexual exposure. Expanded vaccination can be given till 45 years of age as it might prevent against those HPV infections which the female has not contracted yet. If the child is less than 14 years of age then 2 doses (O, 6 months) spaced at least 5 months apart are enough. If the time interval between 2 doses is less than 5 months, then it’s preferable to give the third dose at least 6 months from the 1st dose. If the child is more than 14 yrs of age, then 3 doses are recommended at 0, 1, 6 months or 0, 2, 6 months as per the manufacturer guidelines. In a 3-dose schedule of vaccine, the minimum intervals are 4 weeks between 1st and 2nd dose, 12 weeks between 2nd and 3rd dose, and 5 months between 1st and 3rd dose. If due to any reason, any dose is missed then we don’t have to start all over again but the missed dose can be given up to 1 and a half years. It’s better not to continue the vaccination if a female gets pregnant but it can be administered to lactating females. There is no evidence to abort the pregnancy if a female gets pregnant shortly after the vaccination.
The vaccine is administered intramuscularly in the arm or anterolateral aspect of the thigh. The child should be made to lie down at least for 15 minutes after the shot as rarely fainting or syncopal attacks have been reported. The most common side effects include – injection site redness, swelling or itching, anaphylactic reaction to any component of injection, fever, nausea, gastroenteritis, appendicitis, diarrhea, but very rarely Venous thromboembolic events and Guillan-Barre syndrome have also been reported.
The vaccination coverage of at least 50% can provide a 68% reduction in HPV 16 and 18 and around 60% reduction of anogenital warts. If we are able to achieve HPV vaccination coverage of at least 70% in women, it would be considered as optimum and cost-effective. Please remember that as the vaccine does not prevent against all strains of HPV so regular screening has to be continued as per age-specific guidelines. Also, education of children against the harms of unhealthy sexual practices and the importance of genital hygiene can’t be underestimated.
So, let’s all join hands and take a pledge to eradicate cervical cancer from India. I feel the only monovalent approach to vaccination is not enough. A bivalent approach to screening and vaccination is absolutely essential. Better still would be at least a quadrivalent approach of sexual education, screening, vaccination, and treatment of detected cases. The best approach of all would be a Nanovalent approach of sexual education, screening, vaccination, treatment of all detected cases, reduction of cost of the vaccine and its free availability, robust surrogates to test its efficacy, maintenance of cold chain, the emphasis of vaccination of adolescent girls before sexual exposure rather than vaccination of both boys and girls and development of non-type specific and therapeutic vaccines. I am sure we can win over cervical cancer soon.