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Cervical Cancer and HPV Vaccines, How far have we come ?

By Dr. Kanika Batra Modi in Gynecologic Oncology

Feb 08 , 2022 | 5 min read

Why is it that one of the very few vaccines we have against cancer is not getting a unanimous thumbs-up from everyone, despite it’s presence in the market for nearly 10 years now?

Let’s discuss what are the issues, controversies and final consensus on this vaccine.

Being an inactivated vaccine against viral antigens it provides protection against the most commonly associated strains of HPV, namely 16 and 18 along with the other more common strains depending upton the kind of vaccine taken into consideration. The World Health Organization(WHO) reports there are over a hundred strains of HPV in total and of these 13 are high-risk as they are directly related to cancer.

There are three types of HPV vaccines available:

  • Bivalent – Against the common HPV types, 16 and 18,
  • Quadrivalent – along with the above mentioned strains, it cover 6 and 11 as well, which are associated most commonly with genital warts in both the genders,
  • Nine-valent – which includes these strains apart from the above mentioned ones, 31,33,45,52,58.

And what are the issues with the vaccine?


Safety:

Thanks to a few co-incidental deaths associated in the trials of this vaccine, the stigma scarred the vaccine even before it’s launch. Despite so many studies confirming the safety of the vaccine, it still takes an extra effort for physicians to recommend this vaccine without gulping the whole thing down

  • These vaccines are virus-like particles(VLPs), which are similar to the original the viral capsid. They contain the genetic material and have very well- established safety records.
  • All HPV vaccines have documented safety in various trials and have a large post-licencing data is also available suggesting their safety.


Efficacy:

  • There is a pre-set notion in the minds of laymen and politicians that this vaccine is probably not effective. It has been proven time and again that this vaccine is highly efficacious in preventing cervical, vaginal, vulvar and anal cancer in women. 
  • Gardasil-9, which is unlaunched in India as of now, is active against 9 strains of HPV and is slated to have efficacy of over 90%. 97 to 100 percent among HPV-naïve populations and 44 percent among the overall population 
  • Cervical, vaginal, and vulvar disease — HPV vaccination is effective in preventing cervical disease, including cervical intraepithelial neoplasia (CIN2 or 3) and adenocarcinoma in situ. Vaccine efficacy is greatest in those who do not have prior HPV infection. 
  • Quadrivalent HPV vaccine – Two large, randomized, double-blind trials compared quadrivalent HPV vaccine with placebo among more than 17,000 females aged 15 to 26 . After three years, the efficacy of quadrivalent HPV vaccine for preventing CIN2 or more severe disease due to HPV vaccine types was 97 to 100 percent among HPV-naïve populations and 44 percent among the overall population. Efficacy for preventing VIN2 or 3 and VaIN2 or 3 was similarly 100 percent among HPV-naïve populations and 62 percent among the overall population. 


Cost:

It is one of the major constraints for the introduction of this vaccine. What needs to be realised that the one-time cost of vaccination will help in reduction of many pre-cancerous lesions and cancerous lesions and the costs asscociated in treating them.


Age:

  • It can be admistered from the age of 9 years till 26 years or uptill the woman is sexually inactive.  After sexual exposure the efficacy of vaccine reduces and the woman needs to be informed about higher chances of vaccine failure. Minimum age: 9 years
  • HPV4 [Gardasil] and HPV2 [Cervarix] are licensed and available in India.
  • Only 2 doses of either of the two HPV vaccines (HPV4 & HPV2) for adolescent/preadolescent girls aged 9-14 years;
  • For girls 15 years and older, and immunocompromised individuals 3 doses are recommended
  • For two-dose schedule, the minimum interval between doses should be 6 months.
  • Either HPV4 (0, 2, 6 months) or HPV2 (0, 1, 6 months) is recommended in a 3-dose series for females aged 15 years and older


What Is The Rationale Of Mass Vaccination?

  • There are great number of proposals to include HPV vaccine in the national immunization programme of India.  
  • In the countries that have included HPV vaccination in their immunization programme, studies have suggested that vaccination of the entire United States population of 12-year-old girls would annually prevent more than 200,000 HPV infections, 100,000 abnormal cervical cytology examinations, and 3300 cases of cervical cancer if cervical cancer screening continued as currently recommended. 
  • There is also evidence of herd immunity among males of similar age, reflected by a reduction in genital warts.


What Is The Role Of Hpv Vaccines In Males?

  • HPV vaccination provides a direct benefit to male recipients by safely protecting against cancers that can result from persistent HPV infection.
  •  HPV types 16 and 18 cause nearly 90 percent of anal cancers and substantial proportion of oropharyngeal and penile cancers. 
  • Vaccination with 9-valent or quadrivalent vaccine also protects against anogenital warts (90 percent of which are caused by HPV types 6 and 11). 
  • Among males 22 to 26 years old, catch-up HPV vaccination is recommended if they are men who have sex with men or immunocompromised (including HIV-infected males). Otherwise,"permissive use" of HPV vaccination is recommended for this age range.


Immunogenicity

  •  Excellent antibody responses have been reported following immunization with the 9-valent, quadrivalent, and bivalent vaccines, with seroconversion rates of 93 to 100 percent in females and 99 to 100 percent in males. 


Duration Of Protection

  • HPV vaccines have shown excellent duration of protection for the time periods through which they have been studied. Continued protection against high-grade cervical, vaginal, and vulvar neoplasia has been observed through at least 84 months following vaccination among female trial participants.
  •  Persistent antibody levels and protection against HPV infection have been reported up to 10 years following vaccination. 


Cervical Screening

  • Clinicians should be aware that HPV immunization is not effective in clearing HPV infection, genital warts, or cervical intraepithelial neoplasia that is already present, and the vaccine does not protect against 100 percent of types known to cause cervical cancer. 
  • HPV vaccination status does not impact cervical cancer screening recommendations. 


2-Dose Vs 3-Dose Regime 

  • Three-dose regimens for HPV vaccines are expensive and difficult to complete.
  • The nonrandomized analysis of the nested phase III Costa Rica trial, 4 years after vaccination of women who appeared to be uninfected with bivalent vaccine, provides the first clinical evidence of high efficacy of bivalent HPV vaccine when given in less than three-doses (two doses as well as single dose) in preventing incident HPV-16 and HPV-18 infections that persist for at least 1 year.
  • PATRICIA trials that show similar vaccine efficacy against incident HPV-16/18 infections, 4 years after vaccination, among women 15-25 years, whether the women received one dose, two doses, or three doses. 
  •  A systematic review of alternative vaccination schedules that assessed the seroconversion and seropositivity comparing girls receiving 2-doses with women receiving 3-doses at different time points up to 24 months after vaccination found them to be noninferior at all time-points. 

It’s a long journey that we have to tread upon, but it will be one the most fruitful and game-changing ones in the realm of reducing incidence of one the most dreadful cancers afflicting Indian women, cervical cancer.