16.2 HPV-Related Anogenital Neoplasia, Cervical Screening & Common Gynaecological and Andrological Disorders
Key Takeaways
- High-risk HPV types, above all HPV 16, cause cervical, vulval, penile, and anal intraepithelial neoplasia through E6 degradation of p53 and E7 inactivation of the retinoblastoma protein.
- The LAST terminology divides HPV-related anogenital squamous lesions into low-grade (LSIL) and high-grade (HSIL) squamous intraepithelial lesions, with block-type p16 staining supporting HSIL.
- Differentiated VIN is HPV-independent, arises in lichen sclerosus or lichen planus in older women, and carries a higher risk of invasive cancer than HPV-related vulval HSIL.
- The 2022 EU Council Recommendation advises primary HPV testing for cervical screening in women aged 30 to 65 years at intervals of 5 years or more.
- The ANCHOR trial showed that treating anal HSIL in people living with HIV reduced progression to anal cancer by 57% compared with active monitoring.
Last updated: September 2026
16.2 HPV-Related Anogenital Neoplasia, Cervical Screening & Common Gynaecological and Andrological Disorders
HPV and Cancer
- Low-risk types (mainly HPV 6 and 11) cause about 90% of anogenital warts and low-grade lesions.
- High-risk types (HPV 16, 18, 31, 33, 45, 52, 58, and others) cause cancers of the cervix, vulva, vagina, penis, anus, and oropharynx. HPV 16 is the most important type outside the cervix.
- Oncogenesis: the viral oncoprotein E6 targets p53 for degradation, and E7 inactivates the retinoblastoma protein (pRb). Integration of viral DNA and persistent infection allow progression. Loss of pRb function leads to strong, diffuse ("block-type") p16 staining, a useful marker of HPV-related high-grade disease.
- Risk factors for persistence and progression: smoking, HIV and other immunosuppression (including transplant recipients), and many sexual partners.
Terminology
The Lower Anogenital Squamous Terminology (LAST) system uses a two-tier scheme for all HPV-related squamous lesions of the lower anogenital tract:
| LAST Category | Older Terms | Meaning |
|---|---|---|
| LSIL (low-grade squamous intraepithelial lesion) | CIN 1, AIN 1, VIN 1, flat condyloma | Productive HPV infection; often regresses |
| HSIL (high-grade squamous intraepithelial lesion) | CIN 2–3, AIN 2–3, usual-type VIN, PeIN, Bowenoid papulosis, erythroplasia of Queyrat, Bowen disease | Precancer with a real risk of invasion |
Vulva (ISSVD 2015): vulval LSIL; vulval HSIL (the HPV-related "usual type", in younger women and smokers, often multifocal); and differentiated VIN (dVIN), which is HPV-independent. dVIN arises in lichen sclerosus or lichen planus in older women, often has TP53 mutations, looks subtle, and has a higher and faster risk of invasive cancer.
Penis: HPV-related penile intraepithelial neoplasia (warty or basaloid; clinically Bowenoid papulosis, erythroplasia of Queyrat, or Bowen disease) versus differentiated PeIN linked to lichen sclerosus.
Cervical Screening and Colposcopy
- The 2022 EU Council Recommendation advises primary HPV testing for women aged 30–65 years at intervals of 5 years or more. Younger women (from about 25) may still be screened with cytology in some programmes. Positive HPV tests are triaged with cytology or genotyping.
- Colposcopy examines the cervix after acetic acid (abnormal epithelium turns acetowhite) and sometimes Lugol iodine (abnormal areas do not stain). The transformation zone is where most lesions arise.
- Treatment: CIN 1 is usually observed. CIN 2 in young women may be observed with close follow-up. CIN 3 is treated, most often by large loop excision of the transformation zone (LLETZ). In pregnancy, colposcopy is safe, but treatment is usually deferred until after delivery unless invasion is suspected.
Vulval and Penile HSIL
| Lesion | Treatment Options | Follow-Up |
|---|---|---|
| Vulval HSIL | Wide local excision; laser ablation; topical imiquimod (off-label, supported by trial evidence) | Long-term review; examine cervix and anus as well (field effect) |
| Differentiated VIN | Excision (higher cancer risk) | Treat the underlying lichen sclerosus with very potent topical steroids |
| Penile HSIL / PeIN | Topical 5-fluorouracil or imiquimod, laser, excision, glans resurfacing; circumcision | Examine partners' cervical screening status |
Bowenoid papulosis (multiple small brown papules in young adults) often behaves more benignly than erythroplasia of Queyrat (a solitary velvety red glans plaque in older uncircumcised men), but both are HSIL.
Anal HSIL and Anal Cancer
- Highest-risk groups: MSM and transgender women living with HIV, other people with HIV, women with vulval HSIL or cancer, and solid organ transplant recipients.
- Screening: anal cytology or HPV testing, and digital anorectal examination, followed by high-resolution anoscopy (HRA) with biopsy. International Anal Neoplasia Society guidance (2024) recommends screening the highest-risk groups, for example MSM and transgender women with HIV from about 35 years.
- The ANCHOR trial (2022): in people living with HIV with biopsy-proven anal HSIL, treatment reduced progression to anal cancer by 57% compared with active monitoring.
- Treatment: HRA-guided ablation (electrocautery, infrared coagulation) or topical imiquimod or 5-fluorouracil.
HPV Vaccination
- The nine-valent vaccine covers types 6, 11, 16, 18, 31, 33, 45, 52, and 58.
- Most European countries vaccinate both girls and boys, usually from about 9 to 14 years with two doses, with catch-up programmes and targeted vaccination of MSM. Immunocompromised people receive three doses.
- Vaccination prevents new infections but does not treat existing lesions. It greatly reduces anogenital warts and cervical precancer in vaccinated populations.
Common Gynaecological Disorders Seen in Dermato-Venereology
| Condition | Features |
|---|---|
| Vulvodynia | Chronic vulval pain without a visible cause. Provoked vestibulodynia causes pain at the vestibule on touch (cotton-swab test). Diagnosis of exclusion; managed with education, pelvic floor physiotherapy, topical anaesthetics, and neuropathic agents |
| Vulval dermatoses | Lichen sclerosus, lichen planus, lichen simplex chronicus, psoriasis, and irritant or allergic contact dermatitis |
| Genitourinary syndrome of menopause | Dryness, irritation, dyspareunia, and recurrent urinary symptoms from oestrogen deficiency; vaginal oestrogen helps |
| Bartholin cyst or abscess | Painful swelling at the posterolateral introitus; drainage or marsupialisation |
| Cervical ectropion | Red columnar epithelium on the ectocervix; can bleed after sex; exclude infection and neoplasia |
Common Andrological Disorders
| Condition | Features |
|---|---|
| Pearly penile papules | Rows of small skin-coloured papules around the corona; normal variant (angiofibromas), not warts; reassure |
| Fordyce spots and angiokeratoma of the scrotum (Fordyce) | Benign; sebaceous glands and small red-purple vascular papules |
| Phimosis / paraphimosis | Tight foreskin, often from lichen sclerosus; paraphimosis (retracted foreskin that cannot be replaced) is a urological emergency |
| Peyronie disease | Fibrous plaque of the tunica albuginea causing penile curvature and pain |
| Sclerosing lymphangitis and penile Mondor disease | Cord-like thickening after vigorous sex; self-limiting |
| Epididymo-orchitis and testicular torsion | See the genital infection section; torsion is a surgical emergency |
Test Your Knowledge
A 70-year-old woman with long-standing vulval lichen sclerosus develops a persistent, slightly thickened white-grey area on the left labium minus. Biopsy shows atypia confined to the basal layer, with abnormal keratinisation and negative p16 staining. What is the most likely diagnosis?
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Test Your Knowledge
What did the ANCHOR trial show about anal HSIL in people living with HIV?
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Test Your Knowledge
According to the 2022 EU Council Recommendation, which cervical screening approach is advised for women aged 30 to 65 years?
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Test Your Knowledge
A 22-year-old man is worried about a ring of small, smooth, skin-coloured, dome-shaped papules around the corona of the glans. They have been present for years and are identical in size. What is the correct management?
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