Background

Human Papillomavirus infection is one of the most prevalent sexually transmitted infections worldwide, affecting millions of individuals each year. This diverse group of viruses encompasses more than 100 different strains, some of which can lead to a spectrum of conditions ranging from benign warts to various cancers.

HPV is highly transmissible and predominantly spreads through sexual contact, including vaginal, anal, or oral intercourse. Its complex nature, coupled with its ability to remain latent for extended periods, poses significant challenges in prevention, diagnosis, and treatment. Understanding the intricacies of HPV infection, its associated health risks, and the available preventive measures is crucial in addressing its impact on public health. 

Epidemiology

Prevalence: In the United States, around half of the yearly new HPV infections occur among 15-to-24-year young adults. The likelihood of genital infections is linked to factors such as the total of sexual partners and the age at which individuals begin sexual activity. 

Age Distribution: HPV infections are most acquired shortly after becoming sexually active, typically in late adolescence or early adulthood. However, the peak prevalence occurs in individuals aged 20-24 years. 

Transmission: HPV is primarily transmitted through direct skin-to-skin contact, especially during sexual activity. It can also spread through oral, vaginal, or anal sex. 

Risk Factors: Several factors enhance the likelihood of developing HPV, including a high number of sexual partners, early sexual debut, a weakened immune system, smoking, and certain sexual behaviours. 

Anatomy

Pathophysiology

Transmission: HPV is primarily transmitted through direct skin-to-skin contact, often during sexual activity. Other forms of close contact, such as touching warts on an infected person’s skin or genital area, can also spread it. 

Entry and Infection: The virus enters the body through small cuts, abrasions, or mucous membranes in the skin. Once inside, it infects the basal cells of the epithelium, which are rapidly dividing cells located in the skin or mucous membranes. 

Viral Replication: HPV infects the epithelial cells and undergoes replication in the nucleus of these cells. The virus utilizes the host cell’s machinery to replicate its own DNA. 

Latency and Persistence: After infection, HPV can enter a period of latency where it remains dormant within the host cells. The virus can live for years in certain circumstances without creating any symptoms. During this time, the infected person can unknowingly transmit the virus to others. 

Oncogenic Potential: High-risk HPV types (such as HPV-16 and HPV-18) have been strongly linked to the development of cervical and other cancers.  

Immune Response: In many cases, the body’s immune response can successfully eliminate the virus. However, certain factors can weaken the immune response, allowing the virus to persist and increase the risk of complications. 

Etiology

Sexual Activity: Being sexually active, having multiple sexual partners, or having sexual contact with someone who are having many partners raises the danger of exposure. 

Unprotected Sex: Not using condoms or other barrier methods during sexual activity can heighten the risk of HPV transmission. 

Weakened Immune System: A compromised immune system as a result like HIV/AIDS or medications that suppress the immune system can increase susceptibility to HPV infections. 

Genital Skin-to-Skin Contact: Even without penetrative sex, HPV can be transmitted through genital skin-to-skin contact. 

Early Sexual Activity: Engaging in sexual activity at a young age can increase the likelihood of HPV exposure. 

Genetics

Prognostic Factors

Age: Younger individuals often have a higher chance of naturally clearing HPV infections compared to older individuals. The immune system’s response tends to be more effective in younger people. 

Smoking: Smoking has been linked to a decreased ability to clear HPV infections, potentially leading to persistent infections and an increased risk of developing cervical cancer or other HPV-related diseases. 

Co-infections: Presence of other sexually transmitted infections can influence the course of HPV infection and its outcomes. 

Sexual Behavior: Factors such as the number of sexual partners, early sexual debut, and unprotected sex can influence the risk of acquiring HPV and the likelihood of clearing the infection. 

Clinical History

• Age group 

Human Papillomavirus (HPV) infection can affect individuals of any age group. However, the most common age range for acquiring HPV is during adolescence or early adulthood, typically between the ages of 15 to 24, when individuals become sexually active. 

Physical Examination

Visual Inspection: The healthcare provider might start by visually examining the affected area. For HPV, this often involves examining the genital and anal areas for any visible signs such as warts or lesions. In women, a gynaecological examination may involve using a speculum to examine the cervix. 

Pap Smear/Test (for women): A Pap smear is often done during a gynecological exam to collect cells from the cervix. This test can detect abnormal cervix changes caused by HPV,potentially indicating precancerous or cancerous conditions. 

Biopsy: If there are visible warts or lesions, the healthcare provider may opt to take a small sample (biopsy) of the tissue to send for further examination in a laboratory. This can help confirm the presence of HPV and assess the type and severity of the infection. 

Colposcopy: In cases where abnormalities are found during a Pap smear, a colposcopy may be recommended. 

Age group

Associated comorbidity

Cervical Cancer: Cervical cancer is majorly increased by HPV infection. Persistent infection with high-risk HPV types, especially HPV-16 and HPV-18, can lead to precancerous lesions and, if left untreated, progress to cervical cancer. 

Other Cancers: HPV infection is also linked to other cancers, including anal, vaginal, vulvar, penile, and some oropharyngeal cancers. HPV types 16 and 18 are commonly found in these cancers. 

Genital Warts: Low-risk HPV types can cause genital warts, which are non-cancerous growths on the genitals or in the anal area. These warts can be bothersome but are generally not life-threatening. 

Respiratory Papillomatosis: This is a rare condition caused by HPV infection, resulting in the growth of warts in the respiratory tract, which can affect breathing and require repeated surgeries to remove the growths. 

Immunocompromised Individuals: People with weakened immune systems, such as those with HIV/AIDS or undergoing immunosuppressive therapy, are at increased risk of HPV-related complications and may experience more severe outcomes. 

Sexual Activity and Transmission: HPV is primarily spread via sexual contact, which includes vaginal, anal, and oral intercourse. Having intercourse with several partners or having sex at a young age raises the chance of HPV transmission. 

Associated activity

Acuity of presentation

Genital HPV Infections: 

Genital warts (condyloma acuminata): These are one of the most visible signs of HPV infection. They appear as small growths or clusters of growths in the genital or anal area.  

Abnormal cervical cells: In females, certain high-risk types of HPV can result in aberrant changes in cervix cells. These changes may be detected through routine Pap smears or HPV tests and can progress to cervical cancer if left untreated. 

Non-genital HPV Infections: 

Common warts: These may appear on the hands, fingers, or around the nails. They are rough, raised growths that are often flesh-colored, white, or pink. 

Plantar warts: These form on the soles of the feet and might be painful owing to walking pressure. 

Differential Diagnoses

Genital Warts: This is one of the most common manifestations of HPV infection. Differential diagnosis involves distinguishing these warts from other skin conditions like molluscum contagiosum, skin tags, or seborrheic keratosis. 

Cervical Dysplasia/Cervical Cancer: In women, HPV infection is strongly associated with cervical dysplasia or cervical cancer. Differential diagnosis entails the process of eliminating potential causes of irregular cervical cells or cervical lesions, such as cervical inflammation, cervical polyps, or various types of cervical tumors. 

Oral HPV Infection: HPV can also affect the oral cavity, presenting as oral warts or lesions. Differential diagnosis may involve distinguishing these lesions from oral herpes (HSV-1), canker sores, or other oral infections. 

Respiratory Papillomatosis: In rare cases, HPV can cause benign tumors in the respiratory tract, mainly in the larynx. Differential diagnosis entails separating these tumours from other benign or malignant respiratory tract lesions. 

Anogenital Cancer: HPV infection is linked to various anogenital cancers, such as anal, penile, vaginal, and vulvar cancers. Differential diagnosis involves differentiating these cancers from other non-HPV related cancers or benign conditions affecting these areas. 

Laboratory Studies

Imaging Studies

Procedures

Histologic Findings

Staging

Treatment Paradigm

Medical Procedures: If the HPV infection leads to abnormal cell changes or causes warts, various medical procedures may be used, such as: 

Topical Treatments: For genital warts caused by certain strains of HPV, topical medications like imiquimod, podophyllotoxin, or sinecatechins may be prescribed to remove the warts. 

Cryotherapy: Freezing the warts with liquid nitrogen. 

Surgical Removal: In cases where warts are extensive or don’t respond to other treatments, surgical removal by laser therapy, excision, or electrocautery may be necessary. 

Vaccination: HPV vaccines, like Gardasil are available to prevent certain strains of the virus. They are recommended for adolescents before they become sexually active to provide protection against the most common high-risk HPV strains. 

Treatment of Complications: If HPV leads to more serious conditions such as cervical cancer or other cancers associated with HPV, treatment will involve various options including surgery, chemotherapy, radiation therapy, or a combination of these treatments. 

by Stage

by Modality

Chemotherapy

Radiation Therapy

Surgical Interventions

Hormone Therapy

Immunotherapy

Hyperthermia

Photodynamic Therapy

Stem Cell Transplant

Targeted Therapy

Palliative Care

lifestyle-modifications-in-treating-human-papillomavirus-infection

Vaccination Programs: Encouraging and implementing widespread HPV vaccination programs for adolescents and young adults significantly reduces the prevalence of the virus. Vaccination targeting both males and females before sexual debut has proven effective in preventing HPV infections. 

Sexual Education: Comprehensive sexual education in schools and communities helps individuals understand the risks associated with HPV and how it spreads. Educating about safe sex practices, condom usage, and the importance of regular screenings and vaccinations can play a significant role in prevention. 

Improved Hygiene Practices: Promoting good hygiene habits, including regular handwashing and proper genital hygiene, can reduce the risk of HPV transmission. 

Healthcare Accessibility: Ensuring accessible and affordable healthcare for screenings, early detection, and treatment of HPV-related conditions is vital. Regular screenings for cervical cancer in women and other related HPV diseases can facilitate early intervention. 

Public Awareness Campaigns: Public health campaigns can raise awareness about HPV, its transmission, associated risks, and the importance of vaccination. These campaigns can also help reduce stigma related to HPV infections. 

Effectiveness of immunomodulators in treating human papillomavirus infection

imiquimod 

It is a topical immune response modifier that stimulates the immune system to combat HPV infection. Imiquimod is often used for external genital warts caused by certain types of HPV. It’s applied directly to the affected area and activates the body’s immune response, leading to the destruction of the warts. 

Interferon alfa-n3 & Interferon alfa-2b 

Interferons are proteins produced naturally by the body’s immune system in response to viral infections. They have antiviral properties and can modulate the immune system’s response.

Role of keratolytic agents in treating human papillomavirus

podofilox 

It’s a topical treatment that works by destroying the skin of the wart. It is typically applied directly to the warts and inhibits cell growth, which leads to the death of the wart tissue. 

 It comes in a 0.5% solution and is the active ingredient in podophyllin resin.  

podophyllum resin  

This resin is derived from the roots of certain plants and has been historically used as a treatment for genital warts. However, its use has diminished due to concerns about toxicity and side effects. Podophyllum resin should only be applied by a healthcare professional due to its potential toxicity. 

trichloroacetic acid 85% 

Many medical professionals typically utilize concentrations of 25 to 50% TCA in their practice. However, there are instances where higher concentrations, reaching up to 85%, are employed, followed by neutralization using bicarbonate or water.  

This treatment results in tissue sloughing, followed by a healing process lasting approximately seven to ten days. Notably, TCA therapy is less harmful compared to procedures such as laser surgery, cryotherapy, or electrocautery. 

Effectiveness of antimetabolite, antineoplastics in treating human papillomavirus infection

fluorouracil topical 

The mechanism of action of topical fluorouracil involves inhibiting the synthesis of DNA and RNA in rapidly dividing cells by interfering with the function of an enzyme called thymidylate synthase.

By disrupting the production of nucleic acids necessary for cell replication, fluorouracil can lead to cell death in rapidly dividing cells, such as abnormal or cancerous cells. 

Actinic keratoses is its principal indication for topical therapy. It has been used on adults, especially for warts that have not responded to conventional forms of treatment, even though the USFDA has not approved it for this purpose. 

Use of topical skin products in treating human papillomavirus

sinecatechins 

Sinecatechins is a green tea extract-based medication used primarily for treating external genital and perianal warts (condylomata acuminata). It’s available as an ointment and is applied topically. 

The active ingredient in sinecatechins is derived from green tea leaves, primarily catechins. These catechins have antioxidant properties and are believed to work by modulating the immune response and exerting antiviral effects on the human papillomavirus (HPV), which causes genital warts. 

Effectiveness of Vaccines, viral, inactivated in treating human papillomavirus infection

Human papillomavirus vaccine, nonavalent (Gardasil) 

Nine HPV subtypes— 58,52,45,33,31,18,16,11,6 cause an immunological response based on humoral theory. To prevent infections linked to HPV, routine vaccination is recommended for both females & males between the ages of 9 to 26. Adults between the ages of 27 to 47 are eligible for immunization, and the patient and practitioner collaborate to make these decisions. 

role-of-surgical-procedures-in-treating-human-papillomavirus-infection

Surgical Procedures: In cases where genital warts are large or do not respond to topical treatments, surgical procedures might be considered. Surgical options include: 

Electrosurgery: Using an electric current to burn off warts. 

Laser therapy: Using a focused beam of light to destroy warts. 

Surgical excision: Cutting off the warts. 

role-of-management-in-treating-human-papillomavirus-infection

Prevention: 

Vaccination: HPV vaccination is a major preventive measure that is advised for both men and women. Vaccination can protect against the most prevalent HPV kinds, which cause cancer and genital warts. 

Sexual Safety Practises: Encouragement of condom usage can minimise the risk of HPV transmission, but it does not eliminate the risk because HPV can be transferred through skin-to-skin contact in places not covered by a condom. 

Detection: 

Screening Tests: HPV infection can be detected through various screening methods, including Pap tests and HPV DNA tests. Pap smears can identify abnormal cervical cells caused by HPV, while HPV DNA tests can detect the presence of the virus itself. 

Treatment: 

Monitoring and Observation: In many cases, the body’s immune system can clear the HPV infection without medical intervention. Close monitoring and observation may be recommended, especially for low-risk or asymptomatic cases. 

Medical Interventions: If the HPV infection persists or causes health issues like genital warts or precancerous changes, medical interventions may be necessary. Treatment options may include: 

Topical medications to manage genital warts. 

Procedures such as cryotherapy (freezing), laser therapy, or surgical removal for persistent or problematic genital warts. 

Surgical procedures or other interventions for precancerous or cancerous lesions caused by HPV. 

Follow-Up: 

Regular Monitoring: For individuals with persistent HPV infections or those who have had precancerous changes, regular follow-up appointments with healthcare providers are essential. This helps monitor any recurrence or progression of the infection and ensures timely intervention if needed. 

Lifestyle Recommendations: Healthcare providers may also provide guidance on lifestyle factors, such as quitting smoking and keeping a healthy immune system by eating well and exercising regularly. 

Medication

Future Trends

Media Gallary

References

Human Papillomavirus – StatPearls – NCBI Bookshelf (nih.gov)