Universal Cervical Cancer Immunization: India Ready for a Quantum Leap

Cervical cancer is the fourth-most common cancer in women worldwide. As per the GLOBOCAN (the Global Cancer Observatory) report published in 2020, around 604,127 women were diagnosed with cervical cancer and 341,831 succumbed to death resulting from an advanced stage of the disease across the world.[1] As high as 56% of women eventually succumb to the disease shortly following diagnosis at an advanced stage.[2]

The World Health Assembly, in 2020, envisaged the elimination of cervical cancer as a public health problem and set a target incidence rate of below four per 100,000 women by 2030. One of the targets is full vaccination of 90% of girls with human papillomavirus (HPV) vaccine by the age of 15 years by the year 2030. One hundred and ninety-four countries, including India, have committed to these targets.[3] Interestingly, a South Indian study noted a significantly higher prevalence on the HPV 16 (52%) and HPV 33 (40%) genotypes, with the highly oncogenic HPV 18 subtype detected in only 4% of the samples, indicating that the local prevalence patterns may influence the prevention and treatment strategies.[4]

Current statistics, however, do not paint a sanguine portrait of the Indian scenario. The crude cervical cancer incidence in our country is 18.7 per 100,000 women with a cumulative cervical cancer risk of 2.0%.[5] As a contributor to one-fifth of the global cervical cancer disease burden, India has a steep slope to climb, but that is feasible now with the advent of our own vaccination.

If the WHO life-course approach to health was to be applied to curbing the menace of cervical cancer, an action would be needed from the adolescence to midlife and through all phases of prevention – primordial, primary, secondary, and tertiary.[6]

At present, there is no single comprehensive cervical cancer program or policy in place at the national level. The WHO data reveal that India is severely deficient in the infrastructure and human resource to effectively fight cervical cancer.[4] The NFHS-5 pan-India data reveal that only 1.9% women have ever undergone cervical cancer screening.[7] Therefore, it is imperative to have strategies in place for primordial prevention such as mass immunization before exposure to the risk factors.

Currently, India lacks a national immunization program for carcinoma cervix eradication. However, there are lessons to be learned from both high-income and middle-to-low-income nations which have already imbibed HPV vaccination into their national health programs and are making quantum strides. Since the initiation of the HPV vaccine program in the UK, more than a decade ago, there has been an 86% reduction in HPV infections. In the first decade, 80% of population coverage had been achieved. There was a reduction of genitals warts by 90% in adolescent girls and 70% in adolescent boys, who benefitted indirectly from herd immunity.[8] In 2019, the UK extended this initiative to boys as well. Although the impact on the reduction of cervical cancer is still evolving, the initial trends have shown reduction in rates of preinvasive cervical lesions.

Rwanda’s fight against cervical cancer is an example worth emulating. The universal HPV vaccination of Rwandan school girls and cervical screening of eligible women were initiated in 2011, and to date, 93% have been fully immunized. Since 10 years is a short time span in the disease chronology from HPV infection to cervical cancer presentation, the drop in the incidence rate is expected to the modest at present as the vaccinated subset has yet attained the age of presentation. However, the initial trends show a promising decline. The age-standardized incidence rate has dropped from 34.5 to 31.9 cases per 100,000 women, and the age-standardized mortality rate has dropped from 25.4 to 24.1 per 100,000, respectively.[9]

In India, bivalent and quadrivalent vaccines were introduced in 2008, and nonavalent vaccine was licensed in 2018. India’s initial attempts were marred by unexpected deaths in trial participants, which though unrelated to the vaccine, resulted in the abrupt termination of significant clinical trials and created an unfavorable atmosphere for vaccine uptake.[2] However, focal efforts have now resumed and are showing promising results, as in the state-wise immunization program in Sikkim, an immunization drive in two districts in Punjab, and the opportunistic vaccination of school-going girls by the Delhi Government since 2016.

In Punjab, a cost analysis study estimated the net cost (after treatment savings) for immunizing a 1-year cohort of 11-year-old girls at INR 38 million, with an incremental cost of INR 73 per quality-adjusted life year. A 90% probability was estimated for cost-effectiveness of the vaccination strategy in Punjab at a willingness-to-pay threshold of INR 10,000. The net cost of immunization would account for amount to 0.028% of the state’s health budget.[10]

In Sikkim, a school-based vaccination program conducted using a two-dose schedule achieved >95% HPV vaccination coverage in 9–13 years age girls, and no severe adverse effects were reported.[11]

The Papillomavirus Rapid Interface for Modeling and Economics modeling study demonstrated that the introduction of the national HPV vaccination programs in countries where such programs do not exist will substantially benefit such countries in the prevention of cervical cancer.[12]

Two recent developments promise to help overcome the economic constraints of mass immunization and make vaccine delivery easier, more accessible, and acceptable. Evidence from the observational studies and clinical trial data have established that a single-dose vaccination schedule is noninferior to multidose regimes with sustained antibody levels up to 11 years after vaccination. In April 2022, the WHO Strategic Advisory Group of Experts abridged the HPV vaccination schedule to one or two doses for girls between 9 and 14 years and young females between 15 and 20 years of age,[13] and final recommendations through the WHO position paper on cervical vaccines can be expected only after the consultation with all stake holders.

India recently achieved the technical competence and mass production capability for its indigenous quadrivalent vaccine, “Cervavac,” developed by the Serum Institute of India in coordination with the Department of Biotechnology, Government of India. The Drugs Controller General of India has granted marketing authorization for males and females of the age group of 9–26 years. The vaccine was launched on September 1, 2022. This new vaccine is funded by the Government of India, will be distributed by the state programs, and will later be expanded to the private providers and eventually exported to other nations. It is planned to be provided at a much lower cost of INR 200–400.[14] The vaccination program will be gender neutral and includes boys as it is an important step to reduce the transmission of HPV and protect men from other HPV consequences. Its efficacy as a single-dose vaccine will, however, have to be investigated.

India has an impressive track record in its childhood immunization program, and inclusion of school girls and boys into the national immunization schedule will undoubtedly boost the fight against cervical cancer. A strong political and bureaucratic will and an effective public awareness campaign with positive messaging are imperative for the success of any such endeavor. It will be necessary to bridge the socioeconomic and locoregional barriers to ensure an equitable access for all strata of society. Only then would we be able to gain momentum in the war against cervical cancer.

All these hurdles are not difficult to overcome as India has a solid infrastructure base of health care from the primary to tertiary system and a robust team of health workers. With our vaccine being more cost effective, it would lead onto a universal vaccination for HPV, and we have already proved our capabilities by eradicating polio and small pox.