Table 2 Limitations of the current VLP prophylactic HPV vaccines and some suggested approaches to solve these issues (the limitations discussed here are related mainly to vaccine characteristics, not their social acceptance and similar aspects)

1

Type-specificity (partial)

1. Lack of complete cross-protection against other HPV types that are not included in the vaccine

2. More complex and lengthy manufacturing processes due to the inclusion of multiple types of HPV, which should be produced separately

3. The increased cost of vaccines for adding more HPV genotypes

4. The need for cancer screening remains

5. Risk of emergence of some uncovered HPV types

Employing protective L2 proteins of HPV in the vaccine (either exclusively or in combination with L1) to enhance cross-protection due to the higher conservancy of L2

2

No therapeutic indication

Not indicated for patients who already have cervical cancer

Developing therapeutic vaccines targeting the E proteins of HPV

3

High costs of vaccine

Lower access to vaccines, especially for low-income populations

1. Development of vaccines with lower costs, for example, using simpler hosts (such as E. coli) (already done: Cecolin® and Walrinvax®)

2. Encouraging local production of HPV vaccines in low- and middle-income countries

4

Cold-chain requirement

1. Increasing manufacturing, storage, and transfer costs

2. Not easy handling

1. Lyophilized powder formulations

2. Developing vaccines with more stability at room temperature, such as peptide vaccines

5

Injectable formulation

Need for nurses or other professionals for injecting vaccines

Not preferred by individuals with a fear of injection

Development of non-parental formulations such as intranasal or oral vaccines

6

Need for multiple dosing *

Lower compliance for getting the vaccine, especially in remote areas

1. Optimizing vaccination schedules

2. Reminder or call services

7

Effective only in the early stages of the viral life cycle

Age limitation (The greatest benefit of the vaccine occurs when vaccination is completed before age 15, particularly prior to the onset of sexual activity. However, individuals vaccinated after age 15 still gain some benefit, though it is lower than those who began the HPV vaccine injection before turning 15.)

Development of novel vaccines targeting other proteins that are present in later stages of the disease, such as the E proteins of HPV