Human papillomavirus: how it is transmitted and how to protect yourself

Human papillomavirus (HPV) is the most common sexually transmitted virus, with over 200 types, some of which are highly oncogenic and cause precancer and cancer of the cervix, anal, oropharyngeal, and other types of cancer. The primary goal of modern prevention is to interrupt the chain of infection through vaccination and regular screening, as there is no specific "eradication" antiviral therapy for HPV. [1]

Since 2020, the World Health Organization has been implementing a global strategy to eliminate cervical cancer as a public health problem: vaccinate 90% of girls by age 15, screen 70% of women for HPV by age 35 and 45, and treat 90% of detected precancers and cancers. Achieving these targets could prevent tens of millions of cancer cases over the course of a century. [2]

In clinical practice, HPV infection is most often asymptomatic and resolves spontaneously, but the persistence of highly oncogenic types, especially 16 and 18, is associated with the development of cervical intraepithelial neoplasia and invasive cancer. The risk is increased by immunodeficiency, smoking, and concomitant infections. [3]

Table 1. Key facts about HPV and the global strategy

Question	What is important to know	Source
How many types of HPV are known?	>200, about 40 affect the anogenital and oropharyngeal region	NCI, CDC
Key goals for 2030	90-70-90: vaccination, screening, treatment	WHO
What is the danger of persistence?	Precancer and cancer of the anogenital area and oropharynx	WHO, NCI
[4]

Epidemiology

According to estimates from the Global Cancer Observatory and major reviews, approximately 660,000 new cases and 349,000 deaths from cervical cancer will be registered globally in 2022, with up to 90% of deaths occurring in resource-poor countries. These figures highlight the colossal role of HPV infection as the leading infectious carcinogen for women. [5]

Highly oncogenic types 16 and 18 account for >70% of cervical cancers, and the addition of types 31, 33, 45, 52, and 58 accounts for a significant additional proportion of cases—which is why the nonavalent vaccine has become the standard in most programs.[6]

In oropharyngeal cancer, the proportion of HPV-positive tumors is increasing, especially among men, which requires preventive efforts, although reliable mass screening for this localization does not yet exist. [7]

Vaccination significantly reduces the circulation of vaccine-type HIV, precancerous lesions, and genital warts at the population level, as confirmed by cohort studies and high-coverage countries.[8]

Table 2. Global benchmarks and disease burden

Indicator	Grade	Note
New cases of cervical cancer worldwide	≈662,000 (2022)	Varies by region
Mortality from cervical cancer	≈349,000 (2022)	Up to 90% in low-resource countries
Main oncogenic types	16, 18 (core), plus 31, 33, 45, 52, 58	Coverage with nonavalent vaccine
[9]

Structure of the pathogen

HPV is a small non-enveloped virus with an icosahedral capsid consisting predominantly of the L1 protein and a smaller amount of the L2 protein. The genome is a circular double-stranded DNA of approximately 8 kilobases, encoding the early proteins E1, E2, E4, E5, E6, E7 and the late proteins L1, L2. [10]

Highly oncogenic E6 and E7 proteins interact with cell cycle regulators, disrupting the control of proliferation and apoptosis, which lays the foundation for neoplastic transformation during long-term viral persistence. [11]

L1 capsid proteins form virus-like particles used in prophylactic vaccines; they induce a potent neutralizing immune response without the risk of infection. [12]

Table 3. Genome and functions of key HPV proteins

Gene	Protein	Main function	Significance for the clinic
E1, E2	Replication and transcription control	Support for genome copying	Targets for replication regulation
E5	Modulation of signaling pathways	Increased proliferation	Contribution to pathogenesis
E6, E7	Cell cycle dysregulation	Oncogenic effects	Precancer and cancer with persistence
L1, L2	Capsid	Antigen in vaccines	The basis of neutralization
[13]

Life cycle

The HPV life cycle is closely linked to keratinocyte differentiation. The virus penetrates through microtrauma in the skin or mucosa, attaches to proteoglycans, and enters basal cells, where it forms a low-copy-number persistent virus. As keratinocytes mature, late genes are activated and new viral particles are assembled. [14]

The clinical outcome varies: most often, immune clearance occurs within 1-2 years, but under unfavorable conditions, the infection persists and may progress to intraepithelial neoplasia. [15]

Table 4. Life cycle stages and clinical implications

Stage	Cellular zone	Key event	Clinical meaning
Entrance	Basal layer	Attachment, penetration	Beginning of persistence
Early	Parabasal layer	Genome replication (E1, E2)	Maintaining infection
Late	Surface layers	L1, L2 expression, assembly	Virus isolation
[16]

Pathogenesis

Persistence of highly oncogenic types is accompanied by expression of E6 and E7, which leads to disruption of cell cycle control, genomic instability, and accumulation of mutations. These mechanisms are central to the transition from infection to precancerous and cancerous lesions. [17]

Systemic risk factors for persistence include smoking, immunodeficiency, and concomitant infections, particularly chlamydial infection, which are associated with a higher likelihood of long-term carriage and progression.[18]

Table 5. Factors that enhance the carcinogenic potential of HPV

Factor	Mechanism	Evidence base
Smoking	Modulation of local immunity, carcinogens	Risk factor reviews
Immunodeficiency	Lowering ground clearance	Guides and reviews
Chlamydial infection	Inflammation, persistence	Meta-analyses and cohort data
[19]

Symptoms

The vast majority of infections are asymptomatic and are detected only by screening. Clinical manifestations of low-oncogenic types include anogenital condylomas and, sometimes, laryngeal papillomatosis in children. High-oncogenic types manifest as precancerous changes and, if untreated, invasive tumors. [20]

Oropharyngeal infection may be asymptomatic and only detected in the tumor process; there is no standardized screening for this area, so prevention relies on vaccination and control of behavioral factors. [21]

Table 6. Typical clinical manifestations by type and location

Localization	Low risk	High risk	Comment
Anogenital	Condylomas	Precancer and cancer	Screening is mandatory
Oropharynx	Rarely symptoms until late stages	Oropharyngeal cancer	There is no mass screening
Respiratory tract in children	Recurrent papillomatosis	-	Linked to perinatal transmission
[22]

Stages

The evolution of HPV infection is described using the following sequence: primary infection, transient phase with clearance, persistence, grades 1, 2, and 3 intraepithelial lesions, and invasive cancer. The transition between stages takes years, creating a window of opportunity for screening and treatment of precancer. [23]

Table 7. Conditional stages of the natural course

Stage	Definition	Tactics
Transient	Up to 1-2 years, without persistent changes	Observation, repeat screening
Persistent	Re-identification of one type	Clarifying diagnostics
Precancer grade 2-3	High probability of progression	Ablation or excision
Invasive cancer	Basement membrane ingrowth	Oncological treatment
[24]

Forms

Clinical forms include asymptomatic carriage, anogenital warts, cervical precancerous lesions, anal and vulvar lesions, respiratory papillomatosis in children, and HPV-associated malignancies. The management approach depends on the location and degree of risk. [25]

Table 8. Clinical forms and management guidelines

Form	The main goal	Basic strategy
Asymptomatic carriage	Prevent progression	Age and risk screening
Condylomas	Eliminate symptoms and viral load locally	Patient- and physician-oriented methods
Cervical precancer	Break the progression	Ablation or excision with observation
HPV tumors	Oncological treatment	Team approach
[26]

Complications and consequences

The main complications are the development of precancerous and cancerous lesions of the anogenital and oropharyngeal regions with prolonged persistence of highly oncogenic types. In children, a rare but severe form is recurrent respiratory papillomatosis, associated with types 6 and 11 and perinatal transmission. [27]

The lack of organized screening in low-resource countries maintains high mortality, whereas the combination of vaccination and HPV screening dramatically reduces the disease burden. [28]

Table 9. Key adverse outcomes

Consequence	What is it connected with?	Prevention
Cervical cancer	Persistence of highly oncogenic types	Vaccination and screening
Anal cancer	Persistence and risk factors	Targeted screening in high-risk groups
Laryngeal papillomatosis in children	Vertical transmission types 6 and 11	Maternal vaccination, obstetric tactics
[29]

Diagnostics

The basis of modern screening is testing for HPV DNA of highly oncogenic types as the most sensitive method for primary screening. Intervals and age of onset vary in recommendations, but the trend is toward prioritizing primary HPV testing. [30]

If the test is positive, triage methods are used: cytology, genotyping of 16 and 18, and the double-staining p16 and Ki-67 biomarker test, which increases the sensitivity for detecting precancerous lesions compared to cytology. Colposcopy and targeted biopsy remain the standard for clarifying diagnostics. [31]

There is no mass screening for the oropharyngeal region; HPV status in tumors is determined by p16 immunohistochemistry and molecular methods, which is important for prognosis and treatment selection. For the anal region, risk-stratified guidelines for high-risk groups are published. [32]

A turning point was the approval of vaginal self-collection in health care settings for certain tests in 2024, making screening more accessible; studies in 2025 confirm comparable accuracy of self-collection to clinical collection. [33]

Table 10. Diagnostic approaches and their role

Method	Role	Advantages	Restrictions
HPV test	Primary screening	High sensitivity	Triage is needed
Cytology	Triage and monitoring	Availability	Lower sensitivity
p16 and Ki-67	Biomarker triage	Better sensitivity to precancer	Requires validation and resources
Colposcopy	Verification	Targeted biopsy	Depends on experience
[34]

Differential diagnosis

Condylomas are differentiated from molluscum, seborrheic keratosis, fibropapillomas, and syphilitic condylomas. Precancerous lesions of the cervix are differentiated from reactive and inflammatory changes, as well as atrophic changes in menopausal women. Morphological verification with biomarker assessment is required. [35]

For oropharyngeal lesions, differentiation of HPV-associated tumors from non-tobacco-alcohol-associated tumors is important, which affects prognosis and therapy; the p16 marker is used as a surrogate indicator of HPV. [36]

Table 11. Differential landmarks

Situation	What to confuse with	How to confirm
Anogenital warts	Molluscum contagiosum, keratosis	Dermoscopy, biopsy if in doubt
Cervical precancer	Inflammatory and atrophic changes	Cytology, biomarkers, biopsy
Oropharyngeal tumors	HPV-negative tumors	p16 and molecular confirmation
[37]

Treatment

There is currently no specific systemic "antiviral" medication that clears the body of HPV; clinical manifestations are treated. Anogenital warts are treated with topical medications such as imiquimod, podophyllotoxin, and sinecatechins, as well as cryodestruction, chemical coagulation with trichloroacetic acid, and surgical methods. The choice depends on the size, location, pregnancy, and patient preference. [38]

Precancerous lesions of the cervix are treated with ablation (cryotherapy, thermal ablation) or excision (loop electrosurgical excision, conization) with marginal monitoring and follow-up. In 2021–2025, the effectiveness of thermal ablation was confirmed as an affordable option in screening-triage-treatment programs. [39]

In high-risk men and women, consideration of screening and timely treatment for anal precancers reduces the risk of anal cancer, as shown in a randomized trial of precancer treatment in people with HIV.[40]

In the treatment of HPV-associated tumors, standard oncological approaches are used, including surgery, radiation therapy, and systemic treatment; for some sites, immuno-oncological agents are used. Treatment depends on the stage and status of HPV. [41]

Table 12. Treatment options for clinical situations

Situation	First line	Alternatives	Comment
Condylomas	Imiquimod or podophyllotoxin	Sinecatechins, cryotherapy, surgery	Pregnancy is taken into account
Cervical precancer stage 2-3	Ablation or excision	Personalization	Select by size and transformation zone
Anal precancers in risk groups	Treatment of foci	Dynamic observation	Cancer risk reduction shown
[42]

Prevention

Vaccination is the foundation of primary prevention. In 2022, the World Health Organization updated its position: a single-dose schedule is acceptable for girls aged 9-14 and for young women up to 20 years; two doses for older children; and at least two, preferably three, for those with compromised immune systems. The nine-valent vaccine covers types 6, 11, 16, 18, 31, 33, 45, 52, and 58. [43]

Barrier methods reduce the risk but do not eliminate transmission, as contact is possible on uncovered areas of skin and mucous membranes. Limiting the number of partners, stopping smoking, and treating concomitant infections further reduce the risk of persistence. [44]

Self-collection of vaginal samples in a healthcare setting expands screening coverage and has been shown to be comparable in accuracy to clinical sampling. [45]

Table 13. Preventive measures and strength of evidence

Measure	Effect	Comment
Vaccination	Highly effective against vaccine types	A single-dose schedule is acceptable for adolescents.
Barrier protection	Reduction, but not complete protection	Consistency is important
HPV screening	Early detection of precancer	Self-collection increases reach
[46]

Forecast

In most adults, transient infection resolves spontaneously. The prognosis worsens with the persistence of highly oncogenic types and lack of participation in screening programs. Vaccination-plus-screening-plus-timely-treatment interventions dramatically improve the population prognosis. [47]

For children with recurrent papillomatosis, the course may be prolonged and require repeated interventions, but maternal vaccination and increased vaccination coverage among adolescents potentially reduce the risk of new cases.[48]

Table 14. Prognostic factors

Factor	Influence	Controllability
HPV type and persistence	Highest risk of progression	Managed by screening and treatment
Immune status	Rapid clearance with normal immunity	Correction of risk factors
Participation in programs	Reduction in mortality	Depends on access and awareness
[49]

FAQ

Is it possible to completely cure HPV with medication?
There is no specific systemic drug that clears the body of HPV. Clinical manifestations are treated and progression is prevented through vaccination and screening. [50]

How much protection does a condom provide?
It reduces the risk, but does not eliminate it completely, as HPV is transmitted through skin and mucous contact outside the coverage area. [51]

Who should undergo screening and when?
The priority is primary HPV testing at 5-year intervals within the age limits accepted in the country; if the result is positive, triage with cytology, genotyping, and biomarker tests, followed by colposcopy if indicated. [52]

Can I self-test for HPV?
Yes, some countries allow self-collection of vaginal samples in healthcare facilities for certain tests; studies confirm comparable accuracy. [53]

Is one dose of the vaccine sufficient?
According to the 2022 World Health Organization position, a single-dose schedule is acceptable for adolescents and young women under 20 years of age; two doses are recommended for older people, and at least two for those with compromised immune systems. [54]