Cervical Adenocarcinoma: Key Aspects

• The cervix is the lower one-third of the uterus
• It consists of the endocervix and ectocervix
• The ectocervix has non-keratinized stratified squamous epithelium
• The endocervix has mucus-secreting columnar epithelium with glands

Inflammatory Diseases

• Non-infectious causes include chemicals, tampons, and pessaries
• Infectious causes include:
  • Bacteria: N. gonorrhoeae, Streptococcus, Gardnerella vaginalis, Actinomyces israelii, TB
  • Viruses: HPV, HSV
  • Fungi: Candida, Aspergillus
  • Protozoa: T. vaginalis, Schistosomal sp

Cervicitis

• Usually a mild chronic inflammation
• Involves mixed bacterial flora
• Acute inflammation may result from gonoccocal infection
• Endocervical glands may undergo squamous metaplasia in chronic cervicitis
• Squamous epithelium may show dysplasia

Cervical Erosion (Cervical Ectopy)

• An overgrowth of columnar epithelium replaces the squamous epithelium around the cervical os
• Presents with a raw appearance and velvety feel
• Aetiology includes parturition, contraceptive pills, and persistence of infantile condition
• May be associated with cervicitis

Cervical Dysplasia

• Disorderly but non-neoplastic proliferation of cells
• Characterized by loss in uniformity of individual cells and architectural orientation
• Represents a continuum of change that may end up in frank malignancy if untreated
• Graded as mild, moderate, or severe

Cervical Dysplasia and CIN

• Cervical dysplasia, cervical intraepithelial neoplasia and invasive carcinoma are stages of a continuing process
• CIN I is mild dysplasia, affecting the lower 1/3
• CIN2 is moderate dysplasia, affecting the lower half to 2/3
• CIN 3 is severe dysplasia, affecting >90%
• CIN stands for cervical intraepithelial neoplasia
• Dysplastic changes can extend up to half of the ectocervix
• Mitotic cells may be seen above the basal layer

Clinical Features

• Asymptomatic
• Acetic acid painting of the cervix may show aceto-whiteness in dysplastic epithelium
• Cytological smear tests (Pap smear) are used for screening

Carcinoma In Situ

• Complete loss of stratification and polarity
• Variation in nuclear sizes of cells
• Mitotic figures at all levels
• Starts in the squamocolumnar junction
• Preinvasive phase may last for years
• May not progress to invasion
• Most cases occur in the 4th decade or earlier
• Dysplastic changes start at squamocolumnar junction

Cervical Cancer Screening

• Papaniculaou stain is used to pick dysplastic cells before they become malignant; a screening, non-diagnostic test
• Smear reporting uses the Bethesda system, assessing smear adequacy, presence/absence of dysplastic or malignant cells, and background (presence of microorganisms)
• If taken from the squamocolumnar junction, the smear will have both endo and ecto cervix adequacy; if not, the sample is inadequate

Carcinoma of the Cervix

• Most common malignant tumour of the female genital tract
• 85-95% are squamous cell carcinoma, 5-9% are adenocarcinoma, and 0-5% are adenosquamous cell carcinoma
• Squamous CA arises in the squamocolumnar junction

Risk Factors

• Highest incidence in prostitutes, early age of first coitus, multiple sexual partners, sex with individuals with previous multiple sexual partners and lifetime number of sexual partners
• Minor factors include oral contraceptives, cigarette smoking, family history, associated genital infections, and lack of circumcision in male sexual partner

Viral Infection & CA Cervix

• HPV is associated with various lesions of the cervical squamous epithelium
• HPV 1, 2, 4, and 7 are associated with squamous papilloma
• HPV types 6 or 11 are associated with CIN and condylomata
• HPV types 16, 18, 33 and invasive carcinoma and CIN 3

HPV

• Transforming DNA viruses integrate into the host genome early in their life cycle, transcribing their genes, and forming stable associations
• DNA sequences of HPV types 16, 18, and less commonly 31, 33, 35, and 51 are seen in approximately 95% of invasive squamous cell carcinomas and their precursor lesions (severe dysplasia and carcinoma in situ)
• Some cervical cancers are not associated with HPV infections, but with cigarette smoking and HIV infections
• Cervical cancers are now divided into HPV-associated and non-HPV-associated

Spread of CA Cervix

• Confined to the pelvic cavity until late stages
• Downward extension to the os and vagina
• Lateral extension to the parametrium and ureters
• Anterior and posterior extension to the bladder or rectum, and sacral nerves
• Lymphatic spread to the pelvic lymph nodes

Adenocarcinoma of Cervix

• Endocervical adenocarcinoma accounts for up to 10% of malignant cervical tumours
• Increased incidence has been reported recently, with a mean age at presentation of 56 years
• Most tumours are of the endocervical cell (mucinous) type, but subtypes have little clinical importance
• Adenocarcinoma shares epidemiologic factors with squamous cell carcinoma of the cervix and spreads similarly
• Tumours are often associated with adenocarcinoma-in-situ and are frequently infected with HPV types 16 and 18

Invasive Adenocarcinoma

• Typically presents as a fungating, polypoid, or papillary mass

• Microscopically, exophytic tumours often have a papillary pattern, while endophytic ones display tubular or glandular patterns

• Poorly differentiated tumours are predominantly composed of solid sheets of cells

• Tumour spreads by local invasion and lymphatic metastases

• Overall survival is somewhat worse than that for squamous carcinoma

• Treatment is similar for both carcinoma types

Staging of Cervical CA

• Stage 0: Ca-in-situ (CIN III)
• Stage I: Ca confined to cervix
• Ia: Preclinical Ca, diagnosed only by microscopy
• Ia1: Minimal micro invasion of stroma
• Ia2: Micro invasion of stroma <5mm in depth
• 1b: Histologically invasive of cervix >Ia2
• Stage II: Ca extends beyond the cervix but not into the pelvic wall; involves the vagina but not the lower third
• Stage III: Ca extends into the pelvic wall; there is no cancer-free space between tumour and pelvic wall on rectal exam; involves lower 1/3 of vagina
• Stage IV: Extends beyond the true pelvis, or has involved mucosa of bladder wall or rectum; distant metastases

Staging of Cervical CA

• With current treatment modalities, the 5-year survival rates are:
• Stage I: 80-90%
• Stage II: 75%
• Stage III: 35%
• Stage IV: 10-15%
• Most stage IV patients die due to ureteral obstruction, pyelonephritis and uraemia, not distant metastases

Prevention

• Vaccination: HPV vaccine for girls and boys <15 years, using a 2-dose schedule separated by 6 to 12 months (minimum 5 months interval)
  • One form of vaccine (Gerdasil 9) can be given between 27 and 45 years.
  • Another form (Gerdasil 3) for HPV 16/18 is given in 3 doses over six months for ages 11 and 12.
• Cervical cancer screening: Papaniculaou smear (Pap smear)
• VIA (visual inspection using acetic acid)
• HPV DNA testing

Nomenclature

• CIN I (mild dysplasia) = LSIL
• CIN II (moderate dysplasia) = HSIL
• CIN III (severe dysplasia or ca-in-situ) = HSIL
• L/HSIL: High and low squamous intra-epithelial lesion
• C/N II and III are ASIL

Explore key aspects of cervical adenocarcinoma, including prevalence, HPV associations, microscopic patterns, and the spread of the disease. Understand staging, common causes of death, survival rates, and vaccine protection related to this condition.