Introduction

Cervical cancer is the fourth most common cancer in women worldwide and a major cause of
morbidity and mortality, especially in developing countries. In India, cervical cancer is the second
most common cancer among women, with an estimated incidence of 96,922 cases and 60,078
deaths in 2020. The human papillomavirus (HPV) is the primary cause of cervical cancer, and its
prevention and treatment remain a significant public health issue. Vaccines against HPV have proven
to be effective in preventing HPV infection and related diseases. This article provides an overview of
the current state of HPV vaccine development and implementation in India, with a focus on
landmark clinical trials and recent advances.

Overview of HPV and cervical cancer

HPV is a double-stranded DNA virus that infects the basal cells of the epithelial layer of the skin and
mucous membranes. There are more than 100 types of HPV, of which approximately 40 are
transmitted through sexual contact. High-risk types of HPV, particularly HPV16 and HPV18, are
responsible for more than 70% of cervical cancer cases globally. Other HPV types, such as HPV31,
HPV33, HPV45, HPV52, and HPV58, also contribute to the development of cervical cancer.

Cervical cancer usually develops over a long period of time, starting with pre-cancerous changes in
the cervical cells. These changes can be detected by screening tests such as Pap smear or HPV DNA
testing. If left untreated, pre-cancerous cells can progress to invasive cervical cancer. Symptoms of
cervical cancer may include abnormal vaginal bleeding, pain during sexual intercourse, and vaginal
discharge.

Vaccines for cervical cancer prevention

Currently, there are three HPV vaccines available worldwide: Gardasil, Gardasil 9, and Cervarix.

Gardasil and Gardasil 9 are quadrivalent and nonavalent vaccines, respectively, which protect
against HPV types 6, 11, 16, and 18 (in the case of Gardasil) and against those four types plus five
additional high-risk types (31, 33, 45, 52, and 58) (in the case of Gardasil 9).

Cervarix is a bivalent vaccine that protects against HPV types 16 and 18 only. These vaccines are
highly effective in preventing HPV infection and related diseases, including cervical cancer.
Landmark clinical trials

Clinical trials of HPV vaccines have been conducted in various countries worldwide, including India.
The first HPV vaccine clinical trial in India was conducted in 2007 by the Indian Council of Medical
Research (ICMR). This study enrolled 500 healthy female volunteers aged 10-14 years from two
districts in Gujarat. Participants were randomly assigned to receive either Cervarix or placebo. The
study found that Cervarix was safe, well-tolerated, and highly immunogenic in Indian girls.

In 2009, another clinical trial of Cervarix was conducted in India by GlaxoSmithKline (GSK). This study
enrolled 1,200 healthy female volunteers aged 10-25 years from various parts of India. Participants
were randomly assigned to receive either Cervarix or placebo. The study found that Cervarix was
safe, well-tolerated, and highly immunogenic in Indian girls and women. The results of this study led
to the approval of Cervarix by the Drug Controller General of India in 2009.

In 2012, the first clinical trial of Gardasil in India was conducted by Merck & Co. This study enrolled
1,500 healthy female volunteers aged 10-25 years from various parts of India. Participants were
randomly assigned to receive either Gardasil or placebo. The study found that Gardasil was safe,
well-tolerated, and highly immunogenic in Indian girls and women. The results of this study led to
the approval of Gardasil by the Drug Controller General of India in 2013.

In 2017, a clinical trial of Gardasil 9 was conducted in India by the Indian Society for Colposcopy and
Cervical Pathology (ISCCP). This study enrolled 1,200 healthy female volunteers aged 9-26 years from
various parts of India. Participants were randomly assigned to receive either Gardasil 9 or Gardasil.
The study found that Gardasil 9 was safe, well-tolerated, and highly immunogenic in Indian girls and
women. The results of this study led to the approval of Gardasil 9 by the Drug Controller General of
India in 2018.

Current state of HPV vaccine implementation in India

In India, the National Technical Advisory Group on Immunization (NTAGI) recommends HPV
vaccination for girls aged 9-14 years as a part of the routine immunization program. The HPV vaccine
is given in two doses, six months apart. The vaccine is also recommended for catch-up vaccination
for girls aged 15-26 years who have not been vaccinated before. The vaccine is available in both
private and public healthcare facilities in India.
However, the implementation of HPV vaccination in India faces several challenges, including low
awareness, stigma, and vaccine hesitancy. Some parents and healthcare providers are hesitant to
vaccinate girls against HPV due to misconceptions about the vaccine's safety and efficacy, as well as
concerns about the moral implications of vaccinating girls against a sexually transmitted infection.
There is also a lack of resources and infrastructure to support HPV vaccination programs in many
parts of India.

Recent advances in HPV vaccine development

Several recent advances have been made in HPV vaccine development, including the development
of new vaccines and the introduction of alternative vaccine delivery methods.

One of the most significant recent advances is the development of the nonavalent HPV vaccine,
Gardasil 9, which provides protection against nine HPV types. Gardasil 9 has been shown to be highly
effective in preventing HPV infection and related diseases, including cervical cancer. The vaccine is
currently approved for use in many countries worldwide, including India.

Another recent development is the introduction of alternative vaccine delivery methods, such as
needle-free injection devices and skin patches. These delivery methods may improve vaccine uptake
and reduce needle-phobia and pain associated with traditional needle injections.

Conclusion

HPV vaccines have proven to be highly effective in preventing HPV infection and related diseases,
including cervical cancer. In India, HPV vaccination is recommended for girls aged 9-14 years as a
part of the routine immunization program. Efforts to improve awareness and address vaccine
hesitancy are needed to ensure the successful implementation of HPV vaccination programs in India.
The recent advances in HPV vaccine development, including the nonavalent HPV vaccine and
alternative vaccine delivery methods, provide promising options for improving HPV prevention and
control worldwide.