Trial Information

Prevaccination Distribution of Cervical Human Papillomavirus (HPV) Types and Their Associations With Invasive Cervical Cancer and Its Precursors in Yangtze River Delta Area, China

The incidence of cervical cancer estimated to be 500,000 cases per year with a 50% case
fatality rate. Human papilloma virus (HPV) infection, which is the most common sexually
transmitted viral infection, contributes as a main causative factor to the development of
invasive cervical cancer (ICC) and its precursors (cervical intraepithelial neoplasia, CIN).
Thus, prophylactic HPV vaccines hold great promise to reduce the global burden of cervical
cancer, especially in areas with no or limited screening.

Currently, two prophylactic vaccines, a quadrivalent (Gardasil®, Merck & Co. Inc) and a
bivalent (Cervarix™, GlaxoSmithKline) vaccine, are employed for the prevention of genital
HPV infection in more than 100 countries, and showed high efficacy for the prevention of
target HPV related CIN2+. Merck is also conducting a Phase III trial of a vaccine protecting
against nine types. As the prophylactic efficacy is type-restricted and not all the
different types of HPV are covered by currently available vaccines, determining the
type-specific HPV distribution and their associations with ICC and its precursors would
provide essential information in assessment of HPV vaccination program impact. What is more,
it is possible that the decrease in the prevalence of the target types of these vaccines
could affect the distribution of other types, so the baseline information is also important
for monitoring possible changes in type-specific HPV distribution after vaccination has been
introduced.

Previous meta-analyses had showed that in ICC, HPV 16 was most common, followed by HPV 18,
while HPV 16/18 prevalence was 52% among high-grade cervical lesions. However, the
prevalence of HPV infection varies considerably across the world, and data were limited from
less-developed countries, let alone multi-center studies. Knowledge of the detail pattern of
HPV type-specific distribution in each region will be essential for public health policy
decisions. This will also form the basis for determining which types should be included in
future generation HPV vaccines targeted to specific regions. A tailed HPV vaccine according
to regional prevalence would best serve the population in primary prevention for ICC.

On the other side, while most studies were focus on ICC and high-grade cervical lesions, the
association between HPV types and the progression of CIN1 has rarely been studied. CIN1 is
an insensitive histopathological sign of HPV infection, most of which will spontaneously
regress to normal with host immune system. However, some genotypes have been described as
being more persistent and associated with progression from low-grade lesions to high-grade
lesions, even ICC. Geographical data on type-specific prevalence of HPV in CIN1 with
appropriately designed prospective studies would be helpful in identifying types
preferentially associated with progression to malignancy and accurately predicting the
future impact of vaccination in specific regions.

Recently, a randomized, double-blind trial testing the safety and efficacy of the
quadrivalent vaccine (Gardasil®, Merck & Co. Inc) in Chinese women (V501-041-00) has been
conducting and is proposed to be finished in three years. The bivalent vaccine (Cervarix™,
GlaxoSmithKline) also has applied the phase III double-blind, randomized controlled trial in
Chinese women. These prophylactic vaccines might be licensed and commercially available in
China after trials finish. However, free vaccination supported by the government appears to
be unlikely at present according to current economic status of China. Thus, individuals at
least presently need to pay the cost of vaccines for themselves.

Yangtze River Delta Area, including Shanghai city, Zhejiang Province and Jiangsu Province,
is the most economically developed regions in China. According to media report, the total
GDP in Yangtze River Delta area was approximated 1.064 trillion U.S. dollars in 2010, and
the per capita GDP has exceeded 4,000 U.S. dollars since 2005. As people here have the
highest health awareness and needs, they may become the largest vaccinated population at
their own expense in China. To the best of our knowledge, no multi-center study on HPV
type-specific distribution and their associations with ICC and its precursors is available
in Yangtze River Delta Area, China, except for the mono-center study in Zhejiang Province,
which highlights the need for timely study in this region before large scale vaccination
programs are carried out.