Human papillomavirus (HPV) is a very common virus that can lead to genital warts or certain cancers. There are over 100 different types of HPV, with some causing more serious health problems than others. HPV is primarily transmitted through sexual contact. Most sexually active people will get HPV at some point in their lives if they do not receive the HPV vaccine. However, some people seem to have a natural immunity or resistance to HPV infection.
What is HPV?
HPV stands for human papillomavirus. It is a group of over 150 related viruses. Each HPV virus is given a number to identify it. For example, HPV-16 and HPV-18 are high-risk types that can lead to cancer. HPV-6 and HPV-11 are low-risk types that can cause benign genital warts.
HPV is extremely common – nearly all sexually active individuals will get it at some point. It is estimated that more than 50% of adults have been infected with one or more types of genital HPV.
HPV is primarily spread through sexual contact, including vaginal, anal, and oral sex. It can infect both males and females. HPV can be transmitted even when an infected person has no visible signs or symptoms.
In most cases, the immune system will clear the HPV infection naturally within 1 to 2 years. However, sometimes the infection persists and leads to cellular changes that may progress to cancer. HPV infection causes virtually all cases of cervical cancer and also contributes to cancers of the vulva, vagina, penis, anus, and oropharynx.
Do some people have natural immunity to HPV?
Yes, some individuals appear to have a natural immunity or inherent resistance to HPV infection. Several factors may explain why certain people are less susceptible to acquiring HPV or getting clinical symptoms:
- Genetic differences – Researchers have identified genetic factors, including specific human leukocyte antigen (HLA) alleles, that are associated with resistance to HPV infections.
- Immune response – Some people may mount a more robust initial immune response that clears HPV before it has a chance to persist and cause lesions.
- Microbiome composition – The natural bacteria that reside in the body may influence susceptibility to HPV.
- Behavioral factors – Differences in sexual behavior, such as age at first intercourse, number of partners, and condom use affects HPV exposure and transmission.
Additionally, the risk of infection likely varies between different HPV types. So someone may be naturally resistant to certain high-risk HPV variants but still susceptible to others.
What is the prevalence of natural immunity to HPV?
It is challenging to estimate the exact prevalence of natural immunity because most HPV infections are cleared quickly without causing any symptoms. Large population-based studies found that around 10-30% of women remained HPV negative, despite frequent sexual activity with infected partners over many years.
One study followed female university students for 2.5 years. The results showed:[1]
- 27% repeatedly tested negative for HPV throughout the study.
- 56% became HPV positive at some point during the 2.5 years.
- 17% had at least 3 positive tests, indicating a persistent infection.
The subset that repeatedly tested HPV negative may have some inherent natural immunity or resistance to acquisition and infection. Genetic analysis found certain HLA alleles were more prevalent in the HPV negative group.
What factors influence natural immunity to HPV?
Genetic Factors
Family studies suggest there may be a hereditary element to HPV susceptibility versus natural immunity. Specific human leukocyte antigen (HLA) genes have been implicated.
HLA genes help the immune system distinguish the body’s own proteins from foreign invaders. Certain HLA alleles are associated with increased or decreased risk of HPV infection and cervical cancer development.[2]
For example, the HLA-B7 supertype alleles may offer some protective advantage against HPV infection and associated lesions. Whereas the HLA-DRB1*1501 allele appears to increase susceptibility to HPV-16 and risk of cervical cancer.[3]
Immune Response
Some individuals may generate a more vigorous CD4+ and CD8+ T cell response against HPV upon initial exposure to the virus. This robust adaptive immune reaction likely facilitates rapid clearance of HPV before it has a chance to establish a persistent infection.[4]
Furthermore, high levels of antibodies targeting the HPV capsid proteins L1 and L2 are associated with protection from subsequent HPV infection. So some women may naturally produce more neutralizing antibodies that confer resistance.[5]
Microbiome Composition
The vaginal microbiota composition has been shown to influence a woman’s susceptibility to HPV acquisition and persistence. Lactobacillus species associated with a healthy vaginal flora may enhance the local mucosal immunity against HPV.[6]
Whereas certain bacteria linked to bacterial vaginosis, such as Prevotella and Gardnerella species, are related to increased HPV detection and viral load.[7] The natural vaginal microbiome profile may be one factor modulating natural immunity versus HPV infection risk.
Behavioral Factors
Behavioral factors also likely contribute to variations in HPV susceptibility between individuals:
- Age at first sexual intercourse
- Number of lifetime sexual partners
- Frequency of sexual activity
- Condom usage
- Circumcision status in male partners
- History of other sexually transmitted infections
- Smoking
For example, studies show women who initiated sexual activity at an earlier age are more prone to persistent HPV compared to those with later sexual debut.[8] Having multiple sexual partners increases the probability of encountering HPV. Interestingly, male circumcision is associated with reduced HPV transmission and lower HPV prevalence in female partners.[9]
Can people develop natural immunity to HPV after exposure?
Natural immunity refers to inherent genetic, biochemical, and physiological factors that protect against infection prior to any exposure. But some evidence indicates previous HPV infection may provide some natural immunity against reinfection with the same HPV type:
- Women who naturally cleared an HPV infection have lower rates of re-detection of that same HPV type over the next 6-12 months.[10]
- The risk of acquiring a new HPV type is increased in those with an existing persistent infection. Suggesting transient immunity against additional infections while the immune system is occupied with the initial HPV type.[11]
- Having antibodies against the major HPV capsid proteins L1 and L2 is associated with protection from subsequent HPV infection.[12]
Together this implies that the immune response after natural infection may provide at least short-term immunity against reinfection by the same HPV type. But the strength and duration of this acquired immunity likely varies based on the individual’s genetics, immune function, and HPV type.
Can HPV vaccines provide natural immunity?
HPV vaccines work by stimulating the body to produce neutralizing antibodies against key HPV types. This offers long-lasting protection against new infection without ever having to be exposed to the actual virus.
Clinical trials found the HPV vaccines provide >90% protection against the HPV types targeted by the vaccine. Protection has persisted for at least 10 years with no signs of waning immunity.[13]
In this way, HPV vaccines mimic the natural immunity observed in some individuals by generating antibodies that prevent viral infection upon exposure. So while not exactly “natural” immunity, HPV vaccination provides similarly effective and long-lasting prevention against the HPV types responsible for most cancers.
Who should get the HPV vaccine?
The Centers for Disease Control and Prevention (CDC) recommends routine HPV vaccination for both boys and girls starting at ages 11-12 years old.[14] The vaccine is most effective when administered before any exposure to HPV through sexual activity.
Catch-up vaccination is also recommended for all women up to age 26 years and men up to age 21 years who were not previously adequately vaccinated.
Even if someone has already been infected with one type of HPV, the vaccines can still provide protection against the other HPV types included. So HPV vaccination may benefit many sexually active adolescents and young adults.
However, the vaccine is not recommended for everyone. People with a history of severe allergic reaction to a previous dose of the vaccine or any of its components should not get the HPV vaccine. Immunocompromised individuals should consult their doctor before receiving the vaccine since the effectiveness and safety has not been established in this group.
Conclusion
In conclusion, it appears some individuals do have an inherent natural immunity or resistance to HPV infection. Genetic factors, immune response, microbiome composition, and behavioral factors may all contribute to differences in natural susceptibility versus protection.
Up to 30% of sexually active women remain HPV negative, despite frequent exposure to the virus. This suggests they have some natural immunity against infection and its consequences. Exactly how much protection this confers against cervical cancer is unknown.
The HPV vaccines provide long-lasting immunity against new HPV infection by inducing antibodies against major viral types responsible for cancers. HPV vaccination is recommended for girls and boys starting at 11-12 years old to provide protection before exposure.