Tumours of the cervix
How persistent high-risk HPV transforms the metaplastic cells of the cervical transformation zone, through low- and high-grade intraepithelial lesions, into squamous carcinoma or adenocarcinoma that spreads into the parametria, ureters and pelvic nodes.
By the end, you can
- Describe the ectocervix, endocervix and transformation zone, and explain why the transformation zone is where most cervical tumours begin.
- Explain how the HPV oncoproteins E6 and E7 act on p53 and RB, and relate productive and transforming infection to LSIL and HSIL (CIN 1 to 3).
- Contrast HPV-associated and HPV-independent squamous cell carcinoma and adenocarcinoma of the cervix, including their appearance.
- Trace the local and lymphatic spread of cervical carcinoma and relate it to the general logic of staging.
- Relate bleeding, discharge, pain and kidney failure to the stage of disease that causes them.
- Recognise CIN 1 to 3, adenocarcinoma in situ and the main carcinomas, the FIGO stages and the screening and staging tests, and explain how LLETZ, cone biopsy, surgery, chemoradiotherapy and HPV vaccination act on the mechanism.
What it is
Most cervical tumours are carcinomas of the transformation zone: squamous cell carcinoma from the squamous epithelium and adenocarcinoma from the endocervical glands. Almost all are driven by persistent high-risk human papillomavirus (HPV) through precursor lesions, squamous intraepithelial lesions (LSIL and HSIL, formerly CIN 1 to 3) and adenocarcinoma in situ; a minority, mostly adenocarcinomas, arise independently of HPV.
3 types to tell apart
- HPV-associated carcinomas
- The great majority. HPV 16 and 18 together cause roughly 70% of cervical cancers. The precursors are HSIL and HPV-associated adenocarcinoma in situ, and the tumours show strong, continuous (block) p16 staining.
- HPV-independent carcinomas
- Uncommon: most are adenocarcinomas, chiefly the gastric type, with rare clear cell, mesonephric and squamous forms. They are p16 negative or patchy and are not prevented by measures aimed at HPV.
- Rare non-epithelial and secondary tumours
- Neuroendocrine (small cell) carcinoma, sarcomas, lymphoma, and spread into the cervix from endometrial, bladder or rectal cancer.
US spelling: tumours → tumors, oestrogen → estrogen.
Normal function
Two linings meet at the transformation zone
The is the narrow lower part of the uterus, its lower half projecting into the . The surface facing the vagina, the ectocervix, is covered by non-keratinising stratified squamous epithelium like the vaginal lining. The canal, or endocervix, runs from the to the and is lined by a single layer of tall, mucus-secreting columnar cells that also dip into the stroma as crypts, usually called glands.
The line where the two linings meet, the squamocolumnar junction, moves. Under the oestrogen of puberty and pregnancy the cervix everts, carrying columnar epithelium out onto the ectocervix, where the acidic vagina prompts reserve cells beneath it to become squamous epithelium: squamous metaplasia. The band of metaplastic epithelium between the original and the current junction is the transformation zone; after the menopause it usually retreats into the canal.
Around the cervix lies the parametrium, connective tissue at the base of the broad ligament carrying the uterine vessels, lymphatics and, close beside the cervix, the ureters. The lies in front and the behind. Lymph drains to the parametrial, obturator and iliac nodes, then to the para-aortic nodes.
| Feature | Benign or precursor | Malignant |
|---|---|---|
| Squamous epithelium (ectocervix) | Condyloma (HPV 6, 11); LSIL and HSIL | Squamous cell carcinoma: HPV-associated (most) or HPV-independent (rare) |
| Glandular epithelium (endocervix) | Endocervical polyp; adenocarcinoma in situ | Adenocarcinoma: usual type (HPV-associated); gastric type (HPV-independent) |
| Mixed or neuroendocrine cells | None common | Adenosquamous carcinoma; small cell neuroendocrine carcinoma |
| Stroma and smooth muscle | Leiomyoma | Sarcomas (rare) |
| From elsewhere | None | Direct spread from endometrial, bladder or rectal cancer |
Simplified from the WHO classification (5th edition); squamous cell carcinoma makes up roughly three quarters of cervical cancers and adenocarcinoma most of the rest, varying with region and screening.
Underlying change · Step 1 of 5
High-risk HPV in the transformation zone
The full lesson is part of Student Pro
It takes you through all 5 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Underlying change · Step 2 of 5
LSIL and HSIL: the precursor lesions
The full lesson is part of Student Pro
It takes you through all 5 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Disrupted function · Step 3 of 5
Invasive squamous carcinoma and adenocarcinoma
The full lesson is part of Student Pro
It takes you through all 5 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Disrupted function · Step 4 of 5
Into the parametria, ureters, bladder and nodes
The full lesson is part of Student Pro
It takes you through all 5 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Consequences · Step 5 of 5
Silent precursors, bleeding tumours
The full lesson is part of Student Pro
It takes you through all 5 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Symptoms and signs
Symptoms, signs and findings
The full lesson is part of Student Pro
It takes you through all 5 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Exam detail
Exam detail
The full lesson is part of Student Pro
It takes you through all 5 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Treatment
How treatment works
The full lesson is part of Student Pro
It takes you through all 5 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Recap
Recap
The full lesson is part of Student Pro
It takes you through all 5 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Self-check
Check your understanding
The full lesson is part of Student Pro
It takes you through all 5 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .