HUMAN PAPILLOMAVIRUS IS THE MOST COMMON SEXUALLY TRANSMITTED INFECTION BUT VACCINATION STRONGLY PREVENTS THE FORMATION OF TUMORS

Younes A. Human papillomavirus is the most common sexually transmitted infection but vaccination strongly prevents the formation of tumors.  International Journal of Infection. 2026;10(2):29-33.

A. Younes^*

Anesthesia and Pain Therapy, Medical Center “Mai più Dolore”, Pescara, Italy.

*Correspondence to:
Dr. Ali Younes,
Anesthesia and Pain Therapy,
Medical Center “Mai più Dolore”,
65100 Pescara, Italy.
e-mail: aliyounes@tiscali.it

Received: 01 April, 2026 Accepted: 21 May, 2026

ISSN 3103-6678 [online] Copyright 2026 © by Biolife Publisher This publication and/or article is for individual use only and may not be further reproduced without written permission from the copyright holder. Unauthorized reproduction may result in financial and other penalties. Disclosure: all authors report no conflicts of interest relevant to this article.

ABSTRACT

Human papillomavirus (HPV) infection is the most common sexually transmitted infection and is caused by a DNA virus that infects epithelial cells of the skin and mucous membranes, causing lesions, genital warts, and various types of cancer, although most strains are nonpathogenic. The virus enters the body through small lesions in the epithelium, infects basal cells, and transports its DNA into the nucleus, where it remains separate from the host cell’s DNA. Vaccination can prevent up to 90% of HPV-related cancers, while early detection of changes caused by the virus is made possible by screening tests such as the Pap test. HPV infects basal cells and, once it reaches the nucleus, maintains its DNA in episomal form by expressing early genes (E1, E2, E4, E5, E6, and E7), which allow viral replication and the formation of new viral particles released without cell lysis. In high-risk genotypes, such as HPV-16 and HPV-18, the E6 and E7 oncoproteins inactivate the tumor suppressors p53 and Rb, respectively, compromising DNA repair, apoptosis, and cell cycle control, resulting in uncontrolled proliferation. Furthermore, integration of viral DNA into the host cell genome causes overexpression of E6 and E7, promoting genomic instability, accumulation of mutations, and tumor development. The HPV vaccine, based on virus-like particles (VLPs) of the L1 protein devoid of viral DNA, does not cure the infection but prevents it by inducing a strong immune response with the production of neutralizing antibodies and protecting against the main HPV types responsible for cancers and genital warts. Vaccination, recommended especially before the onset of sexual activity and recommended for ages 9 and up, including for immunocompromised individuals, represents, along with screening, one of the most effective tools for reducing the risk of precancerous lesions and HPV-related cancers.

KEYWORDS: Human papillomavirus, HPV, infection, tumor, vaccination

INTRODUCTION

Human papillomavirus (HPV) infection is the most common sexually transmitted infection (STI), but it can now be prevented through vaccination, which prevents the onset of HPV-related cancers by up to 90% (1). HPV is a DNA virus belonging to the papillomaviridae family of non-enveloped double-stranded DNA viruses responsible for epithelial infections that can lead to cancers, including cervical, anal, oropharyngeal, penile, and vulvar cancers (2). Most types of HPV are non-pathogenic, however some types can cause lesions and/or genital warts, in addition to tumors (3).  Pathological changes caused by HPV can be clinically detected with various methods, such as a Pap test after a positive test result, which allows for the early identification of alterations caused by HPV (4).

HPV can infect both skin and mucous membrane epithelial cells (5). It enters the human body through small lesions in the epithelium, where it infects basal cells, small round cells located in the deepest layer of the epidermis (6). After the viral DNA enters the cytoplasm, it reaches the nucleus, where it remains as circular DNA separate from cellular DNA (7).

DISCUSSION

In HPV-infected host cells, interactions occur between viral proteins and host cell regulatory proteins. Once inside, the double-stranded DNA virus reaches the nucleus, where it remains in episomal form and expresses the early genes E1, E2, E4, E5, E6, and E7, which enable viral replication (8) (Table I).

Table I. Most important early proteins of human HPVs.

Cell division leads to increased copying of the viral DNA, and capsid levels also increase. At this point, the structural proteins L1 and L2 form the viral envelope, and new viral particles assemble (9).  These are released when surface cells shed, without causing cell lysis. High-risk viral strains such as HPV-16 and HPV-18 are those with the highest incidence of tumors (10).

The E6 oncoprotein prevents tumor suppressor action; it binds to a ubiquitin ligase, the cellular protein E6-AP, forming a complex that recognizes the p53 protein, ubiquitin, and induces its degradation by the proteasome (11).  Furthermore, E6 induces the degradation of p53, causing DNA damage and the cell’s ability to arrest its cell cycle and undergo apoptosis. The viral protein E7 is also very important. It binds to the retinoblastoma protein (Rb), triggers the release of E2F transcription factors, and mediates the cell’s entry into S phase, causing it to proliferate abnormally (12,13). Inactivation of Rb by E7 releases E2F, the genes required for DNA synthesis are transcribed, and the cell continuously enters the S phase. These aforementioned effects lead to a combined action of E6 and E7, causing accumulation of genetic mutations, genomic instability, uncontrolled proliferation, and the possible onset of tumors after about a couple of years (14).

HPV-16 and HPV-18 are high-risk genotypes in which the viral DNA can integrate into the cellular genome (10). E6 and E7 are produced in excess, the E2 gene is disrupted, and control over E6 and E7 expression is lost. Excessive E6 and E7 activity causes genomic instability; inactivation of p53 and Rb, uncontrolled cell proliferation, cell immortalization, and probable tumor formation (as for example in HPV infection of the uterine cervix) (15,16).

In summary, the virus enters the basal cell, provokes the expression of E1-E2-E5-E6-E7 proteins and the induction of E6 and E6-AP (p53 degradation), causing decreased levels of apoptosis and DNA repair. E7 binds to Rb with the release of E2F, continuation of the S phase, uncontrolled replication, and tumor formation. This is an important classic molecular mechanism describing the inactivation of the two main cellular tumor suppressors, p53 (by E6) and Rb (by E7) (Fig.1).

Fig. 1. Steps illustrating the process in which viral entry into the cell can lead to tumor formation.

VACCINATION

The HPV vaccine is a vaccine that prevents and protects against infection by certain types of HPV, which causes various cancers and genital warts (17). The vaccine consists of virus-like particles (VLPs) derived from the L1 protein of the viral capsid and is not curative but prevents infection (18). VLPs do not contain viral DNA, are non-infectious, and cannot cause disease, but they induce a strong immune response with the production of neutralizing antibodies (19).

The most widely used vaccine today is the nine-valent vaccine, which protects against nine types of HPV (20).  For maximum effectiveness, HPV vaccination should be administered before the onset of sexual activity for both girls and boys, generally between the ages of 11 and 12, but can also be administered at later ages (1). Vaccination is essential because, along with screening, it is one of the most effective tools for protecting patients from dangerous HPV-related cancers (1).

Today, in many European countries, such as Italy, where incidence of tumors caused by HPV is growing, vaccination is free for both male and female adolescents from their eleventh birthday (21) (Table II). Women who have been treated for CIN2+ or higher lesions can also benefit from the free national plan (22). The vaccine is indicated for the active immunization of individuals aged 9 years and older against HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58, and against the following HPV-related diseases: precancerous lesions and cancers affecting the cervix (23).

Table II. Incidence of tumors caused by the human papilloma virus (HPV) per year in Italy.

HPV vaccination is strongly recommended for immunocompromised individuals, such as those with HIV infection, organ transplant recipients, and patients receiving immunosuppressant drugs, as they are more vulnerable (24).  Immunocompromised individuals are at a higher risk of becoming infected, developing serious infections, and are more likely to develop HPV-related precancerous lesions and cancers (25).  The most suitable vaccine for immunocompromised individuals is the inactivated VLP vaccine, which is safer even in immunosuppressed patients (26).

CONCLUSIONS

Integration of HPV viral DNA into the host cell genome is a frequent event in tumors associated with high-risk HPV strains. this often leads to the loss of the viral E2 gene, which normally limits the expression of E6 and E7, resulting in overexpression of these oncoproteins and an increased risk of neoplastic transformation. Vaccination is important for preventing the spread of HPV and its associated tumors.

Conflict of interest

The author declares that they have no conflict of interest.

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