Overview
Human Papillomavirus (HPV)
1. Clinical Overview
Summary
Human Papillomavirus (HPV) is a double-stranded DNA virus belonging to the Papillomaviridae family. Over 200 HPV genotypes exist, with approximately 40 infecting the genital tract. HPV is the most common sexually transmitted infection (STI) worldwide, with most sexually active individuals acquiring it at some point. Most HPV infections are transient and asymptomatic, clearing spontaneously within 1-2 years. However, persistent infection with high-risk (oncogenic) HPV types, particularly HPV 16 and 18, can lead to Cervical Cancer, as well as Vulvar, Vaginal, Penile, Anal, and Oropharyngeal cancers. Low-risk HPV types (Especially HPV 6 and 11) cause Genital Warts (Condylomata Acuminata) and Laryngeal Papillomatosis. Prevention through HPV Vaccination is highly effective and is now part of routine childhood immunisation programmes. Cervical Screening (Formerly Pap smear, Now HPV-based) aims to detect precancerous changes (CIN) before progression to cancer. [1,2,3]
Clinical Pearls
"HPV 16/18 = Cancer Risk": High-risk types cause ~70% of cervical cancers and significant proportion of other anogenital and oropharyngeal cancers.
"HPV 6/11 = Warts": Low-risk types cause ~90% of genital warts. Not oncogenic.
"Vaccine Prevents Cancer": HPV vaccination prevents infection, Warts, CIN, and Cervical/Other cancers. Highly effective.
"Most Infections Clear": ~90% of HPV infections clear spontaneously within 2 years. Persistent infection is the risk.
2. Epidemiology
Demographics
| Factor | Notes |
|---|---|
| Prevalence | Most common STI. ~80% of sexually active individuals infected at some point. |
| Peak Incidence | Late teens to early 20s. Shortly after sexual debut. |
| Genital Warts | Peak 20-24 years. Declining with vaccination. |
| Cervical Cancer | Median age ~50 years (Result of persistent infection over decades). |
Transmission
| Route | Notes |
|---|---|
| Sexual Contact | Primary route. Genital-genital, Oral-genital, Manual-genital. Skin-to-skin. Condoms reduce but do NOT eliminate risk (Exposed skin). |
| Vertical (Mother-to-Child) | Rare. Can cause Juvenile-onset Laryngeal Papillomatosis. |
| Fomites | Unlikely but possible (Cutaneous warts). |
3. HPV Types and Associated Diseases
Classification
| Category | Types | Associated Diseases |
|---|---|---|
| High-Risk (Oncogenic) | 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68 | Cervical Cancer, Vulvar Cancer, Vaginal Cancer, Penile Cancer, Anal Cancer, Oropharyngeal Cancer, CIN, VIN, VAIN, AIN. |
| Low-Risk (Non-Oncogenic) | 6, 11, 42, 43, 44 | Genital Warts (Condylomata Acuminata), Laryngeal Papillomatosis. |
HPV-Related Cancers (Proportion)
| Cancer | % Attributable to HPV |
|---|---|
| Cervical Cancer | ~100% (Virtually all are HPV-related). |
| Anal Cancer | ~90%. |
| Oropharyngeal Cancer | ~70% (Rising incidence). |
| Vaginal Cancer | ~70%. |
| Vulvar Cancer | ~40-50%. |
| Penile Cancer | ~40-50%. |
4. Clinical Presentation
Asymptomatic Infection
Genital Warts (Condylomata Acuminata)
| Feature | Notes |
|---|---|
| Caused By | HPV 6 and 11 (Low-risk). ~90% of cases. |
| Appearance | Fleshy, Soft, Cauliflower-like (Papillomatous) OR Flat, Keratotic. Skin-coloured, Pink, or Hyperpigmented. |
| Location | Males: Penis, Scrotum, Perianal. Females: Vulva, Vagina, Cervix, Perianal. |
| Symptoms | Often asymptomatic. May cause Itching, Discomfort, Cosmetic concern. |
| Diagnosis | Clinical (Appearance). Biopsy if atypical, Pigmented, Refractory, Or suspicion of malignancy. |
Cervical Intraepithelial Neoplasia (CIN) / Cervical Cancer
| Feature | Notes |
|---|---|
| Caused By | High-risk HPV (16, 18 predominantly). |
| CIN 1/2/3 | Precancerous changes. Detected by screening. Often asymptomatic. |
| Cervical Cancer Symptoms | Post-coital bleeding, Intermenstrual bleeding, Abnormal vaginal discharge, Pelvic pain (Late). |
Oropharyngeal Cancer
| Feature | Notes |
|---|---|
| Rising Incidence | Especially HPV 16. Tonsil and Base of tongue. |
| Presentation | Sore throat, Dysphagia, Neck mass (Lymph node), Otalgia. |
Laryngeal Papillomatosis
| Feature | Notes |
|---|---|
| Caused By | HPV 6 and 11. |
| Juvenile-Onset | Vertical transmission. Presents in childhood with Hoarse voice, Stridor, Respiratory distress. |
| Adult-Onset | Sexual transmission. Hoarseness. |
Most Common
Majority of HPV infections are subclinical and transient.
5. Investigations
Genital Warts
| Test | Notes |
|---|---|
| Clinical Diagnosis | Usually sufficient based on appearance. |
| Acetic Acid (Acetowhitening) | Application highlights subclinical lesions (Research/Specialist use). |
| Biopsy | If atypical, Pigmented, Ulcerated, Refractory, Or suspicion of malignancy (VIN, VAIN, SCC). |
| HPV Typing | Not routinely done for warts. |
Cervical Screening (HPV-Based)
| Test | Notes |
|---|---|
| HPV Primary Screening | Now standard in UK for cervical screening. Tests for high-risk HPV DNA/RNA. |
| Cytology (Liquid-Based Cytology – LBC) | If HPV positive → Cytology performed reflexively. Detects abnormal cells (Dyskaryosis). |
| Colposcopy | If cytology abnormal or persistent HPV. Direct visualisation of cervix. Biopsy. |
Cervical Screening Programme (UK)
| Age Group | Frequency |
|---|---|
| 25-49 years | Every 3 years. |
| 50-64 years | Every 5 years. |
| >65 years | Exit if adequate negative history. |
6. Management
Management Algorithm
HPV-RELATED CONDITION
↓
┌────────────────┴────────────────┐
GENITAL WARTS HIGH-RISK HPV / CIN
↓ ↓
GENITAL WART TREATMENT CERVICAL SCREENING PATHWAY
┌──────────────────────────────────────────────────────────┐
│ **PATIENT APPLIED** │
│ - Podophyllotoxin (Warticon) 0.5% cream/Solution │
│ Apply BD for 3 days, 4 days off. Repeat up to 4 cycles│
│ - Imiquimod (Aldara) 5% cream │
│ Apply 3x/week at night. Up to 16 weeks. Immune modifier│
│ │
│ **CLINICIAN APPLIED** │
│ - Cryotherapy (Liquid nitrogen) │
│ - Electrosurgery / Diathermy │
│ - Excision │
│ - Trichloroacetic Acid (TCA) │
│ - Laser ablation (Specialist) │
│ │
│ **Recurrence**: Common (~30%). May need repeated treatment│
│ **Partner Notification**: Discuss. Current partners. │
│ **STI Screening**: Offer full screen. Check for other STIs│
└──────────────────────────────────────────────────────────┘
↓
CERVICAL SCREENING FOLLOW-UP
┌──────────────────────────────────────────────────────────┐
│ **HPV Positive, Cytology Negative** │
│ - Repeat at 12 months │
│ - If persistent HPV → Colposcopy │
│ │
│ **HPV Positive, Cytology Abnormal** │
│ - Colposcopy │
│ │
│ **CIN1** │
│ - Often conservative management (May regress) │
│ - Repeat cytology/Colposcopy at 12 months │
│ │
│ **CIN2/CIN3 (High-Grade)** │
│ - **LLETZ (Loop Excision)** / Cone Biopsy │
│ - Excision and histological assessment │
│ - Surveillance post-treatment │
│ │
│ **Cervical Cancer** │
│ - MDT management (Surgery +/- Chemoradiotherapy) │
└──────────────────────────────────────────────────────────┘
Prevention (Key Strategy)
| Measure | Notes |
|---|---|
| HPV Vaccination | Highly Effective. Prevents infection, Warts, CIN, Cancers. |
| Cervical Screening | Detects precancerous changes. Secondary prevention. |
| Condoms | Reduce risk but do not eliminate (Exposed skin). |
| Limiting Partners | Reduces exposure risk. |
7. HPV Vaccination
UK Vaccination Programme
| Aspect | Details |
|---|---|
| Current Vaccine | Gardasil 9 (9-valent). Covers HPV 6, 11, 16, 18, 31, 33, 45, 52, 58. |
| Who | All children aged 12-13 years (Year 8). Single dose now (Previously 2 doses). |
| Catch-Up | Available for those who missed. MSM up to age 45 (Via sexual health clinics). |
| Efficacy | >90% protection against targeted types. Prevents ~90% of cervical cancers. |
Vaccine Types
| Vaccine | Types Covered |
|---|---|
| Cervarix | 16, 18 (Bivalent). |
| Gardasil 4 | 6, 11, 16, 18 (Quadrivalent). |
| Gardasil 9 | 6, 11, 16, 18, 31, 33, 45, 52, 58 (Nonavalent). UK standard. |
8. Complications
| Complication | Notes |
|---|---|
| Cervical Cancer | Major consequence of persistent high-risk HPV. Preventable. |
| Other Anogenital Cancers | Vulvar, Vaginal, Anal, Penile. |
| Oropharyngeal Cancer | Rising. HPV 16. |
| Laryngeal Papillomatosis | Rare. Recurrent respiratory tract lesions. |
| Psychosocial Impact | Stigma, Anxiety associated with genital warts or HPV diagnosis. |
9. Prognosis and Outcomes
| Factor | Notes |
|---|---|
| Clearance | ~90% of HPV infections clear within 2 years. |
| Genital Warts | Often recur (~30%). Eventually clear in most immunocompetent individuals. |
| CIN | CIN1 often regresses. CIN2/3 have higher progression risk to cancer if untreated. |
| Cancer Prevention | Vaccination highly effective. Screening prevents most cervical cancer deaths. |
10. Evidence and Guidelines
Key Guidelines
| Guideline | Organisation | Key Recommendations |
|---|---|---|
| Cervical Screening | NHS CSP / PHE | HPV primary screening. Colposcopy for high-risk/Abnormal cytology. |
| HPV Vaccination | JCVI / Green Book | Universal vaccination. Gardasil 9. Single dose. |
| Genital Warts | BASHH | Topical treatment (Podophyllotoxin, Imiquimod) or Cryotherapy. STI screening. |
11. Patient and Layperson Explanation
What is HPV?
HPV (Human Papillomavirus) is a very common virus. There are many types. Most people will get HPV at some point, And usually their body clears it without any problems.
How is it spread?
HPV is spread through skin-to-skin contact, Usually sexual. Condoms help but don't fully protect because they don't cover all the skin.
What can HPV cause?
- Genital Warts: Caused by low-risk types (HPV 6 and 11). Not dangerous but can be bothersome.
- Cervical and Other Cancers: Caused by high-risk types (HPV 16 and 18). This is why screening and vaccination are so important.
How can I protect myself?
- HPV Vaccine: The best protection. Given to teenagers. Prevents most HPV-related warts and cancers.
- Cervical Screening: Regular smear tests detect any changes early, Before cancer develops.
Do I need treatment?
- Most HPV infections: Clear on their own. No treatment needed.
- Genital Warts: Can be treated with creams or by freezing.
- Abnormal Smear: May need further tests and sometimes a small procedure to remove abnormal cells.
12. References
Primary Sources
- Public Health England. HPV vaccination programme. Green Book Chapter 18a. 2022.
- BASHH. UK National Guideline on the Management of Anogenital Warts. 2015 (Updated 2021).
- Schiffman M, et al. Human papillomavirus and cervical cancer. Lancet. 2007;370(9590):890-907. PMID: 17826171.
13. Examination Focus
Common Exam Questions
- Oncogenic Types: "Which HPV types are responsible for most cervical cancers?"
- Answer: HPV 16 and 18 (Cause ~70% of cervical cancers).
- Wart-Causing Types: "Which HPV types cause most genital warts?"
- Answer: HPV 6 and 11.
- Vaccine Coverage: "What does Gardasil 9 cover?"
- Answer: HPV 6, 11, 16, 18, 31, 33, 45, 52, 58.
- Cervical Screening: "What is the current cervical screening strategy in the UK?"
- Answer: HPV Primary Screening. If HPV positive → Cytology. If cytology abnormal → Colposcopy.
Viva Points
- Persistence is Key: Most HPV clears. Persistent high-risk HPV = Cancer risk.
- Vaccine Prevents Cancer: Gardasil 9 prevents ~90% cervical cancers.
- Screening Detects CIN: Before it becomes cancer.
- Warts ≠ Cancer Risk: Low-risk HPV (6, 11) does NOT cause cancer.
Medical Disclaimer: MedVellum content is for educational purposes and clinical reference. Clinical decisions should account for individual patient circumstances. Always consult appropriate specialists.