Cervical Malignancy

1. Cervical Malignancy
Dr. Indranil Bhattacharya
Consultant Pathologist
Dept. of Pathology
Jagjivan Ram Hospital
Mumbai

2. Definition/Description
Carcinoma of the cervix is a malignancy arising
from the cervix
• The cervix connects the uterus with the vagina.
• The endocervix is the portion of the cervix closest
to the uterus whereas the exocervix or ectocervix
is closest to the vagina.
• The cervix is covered in two main types of cells:
squamous cells found on the exocervix, and
glandular cells on the endocervix.
• Squamous and glandular cells come together at the
area known as the transformation zone. It is here
where most cervical cancers originate.
• Gradually, the normal cells lining this area develop
pre-cancerous changes that transform into cancer.
Cervical cancer typically grows at a slow rate and
presents asymptomatically

3. Epidemiology
• Cervical cancer continues to be listed among the top
gynecologic cancers worldwide.
• According to current data, it is ranked fourteenth among all
cancers and fourth-ranked cancer among women worldwide
• Globally, there are more than 500,000 new cases of cervical
cancer annually.
• Approximately 250,000 women die of cervical cancer annually.
• In the United States, about 4000 women die from cervical
cancer annually. The causative agent is a sexually transmitted
viral infection.
• Cervical cancer mortality is higher among women who have not
been screened in the last five years and those women without
consistent follow-up post identification of a precancerous lesion.

4. • Cervical cancer is the most common cause of gynecological
cancer-related death worldwide
• Mortality rates have decreased significantly in the United States
(more than 45% since the early 1970s).
• 80% to 85% of cervical cancer-related deaths occur in
developing countries.
• Pre-invasive carcinoma in situ (no invasion of surrounding
tissues) is more common in women 30-40 years of
age. Invasive carcinoma is more frequent in women over 40
years of age.
• Women ages 65 and over account for 25% of new cases of
cervical cancer.

5. Etiology
• Human papillomavirus (HPV) is found in the majority
of sexually active people at some point during their
life. There are more than 130 types of known HPV
with 20 HPV types identified as cancer-related.
• HPV-related cervical dysplasia rates are only known
in women since men are not screened outside of
research protocols.
• HPV 16 and 18 are the most commonly found HPV in
invasive cervical cancer.
• The greatest prevalence of high-risk HPV occurs in
the young adult period before 25 years of life and
cervical cancer death peaks in the middle age period
of 40 to 50 years of life

6. Risk Factors
• Human papillomavirus (HPV) 16 and 18 infections
• Multiple sexual partners or a male partner with multiple
previous or current sexual partners
• Young age at first intercourse
• High parity
• Immunosuppression
• Certain HLA subtypes
• Oral contraceptives
• Nicotine (smoking)

7. Characteristics/Clinical Presentation
Presenting symptoms include:
• Vaginal bleeding
• Vaginal discharge
• Subclinical: an abnormal cervical cancer screening test

8. Clinical Staging for Cervical Cancer
Cervical cancer is staged by the International Federation of Gynecology
and Obstetrics (FIGO) staging system, based on clinical examination
rather than surgical findings.
Revised FIGO staging of cervical carcinoma 2018:
• FIGO no longer includes Stage 0 (Tis).
• I: confined to cervix (extension to the corpus should be disregarded).
• II: beyond the uterus, but has not extended onto the lower third of the
vagina or to the pelvic wall.
• III: carcinoma involves the lower third of the vagina and/or extends to
the pelvic wall and/or causes hydronephrosis or non‐functioning
kidney and/or involves pelvic and/or paraaortic lymph nodes.
• IV: carcinoma has extended beyond the true pelvis or has involved
(biopsy proven) the mucosa of the bladder or rectum.

10. Treatment and
prognosis
Prognosis is affected by many
factors which include:
• Tumour stage
• The volume of the primary mass
• Histologic grade
• Five-year survival rates vary
between 92% for stage I
disease and 17% for stage IV
disease

11. Screening Tests
Cervical cancer screening is one of the best cancer prevention
achievements. However, there continue to be women who are not compliant
with screening recommendations. Many die from this preventable cancer
due to inadequate screening.
• According to the United States Preventative Services Task Force (USPTF),
Pap screening is recommended beginning at age 21 years of age.
• HPV testing begins at age 30 in conjunction with Pap smear cytology.
• Screening is recommended every three years for women with continued
normal screening and those low risk for cervical cancer.
• For women over 30 years of age, cytology can be every five years
with HPV testing.
• Level A recommendation or women with low-risk status and consistent
normal screenings can discontinue cervical cancer cytology and HPV
testing at age 65.
• Women who have had a total abdominal hysterectomy including removal of
the cervix for benign disease do not require further screening.

12. Systemic Involvement
• Cervical cancer affects the female reproductive system.
• Pressure from tumor on neighboring structures can affect the
urinary system and gastrointestinal system (bowel).
• Metastasis may occur to the central nervous system (CNS),
pulmonary system, urinary system (bladder), gastrointestinal
system (rectum), retroperitoneal lymph nodes, paracervical
lymphatics and parametrial lymphatics.

13. Medical Management
• Precancerous lesions are managed conservatively for those women younger than 25 years.
• The majority of abnormal findings in women younger than 25 are low-risk cervical dysplasia and
will resolve spontaneously.
• Colposcopy evaluates persistent, abnormal cytology or lesions suspected to be greater than low
risk. These are managed according to findings.
• Low-risk lesions may be watched and reevaluated more frequently
• High-risk lesions are treated based on size, location, and staging.
• Cryotherapy or excision is done to manage pre-cancerous lesions that are limited in size and
depth.
• Conization, laser or Loop Electrosurgical Excision Procedure (LEEP) are used in managing
those lesions that include the endocervical canal and are more extensive.
• LEEP may provide better visualization of the squamocolumnar junction and provide the benefit
of less bleeding in the outpatient setting.
• If cancer is diagnosed, the next step in management is staging to determine further treatment.
• Treatment of early-stage disease includes a radical hysterectomy.
• For women who desire pregnancy with early-stage disease, conization may be the initial
treatment.
• Chemotherapy and radiation are usually the next steps in treatment after hysterectomy to slow
the growth of cancer

14. Differential Diagnosis
Benign Conditions
• Polyps
• Cervical conditions (infections, polyps, myomas)
• Iatrogenic (birth control pills, HRT, IUD)
• Cervical ectopic pregnancy (consider with women of childbearing age)
Malignant Conditions
• Endometrial cancer with cervical invasion
• Other cervical malignant condition (sarcoma, lymphoma, metastasis)
• Invasion of the cervix from other organs in proximity:
• Bladder cancer
• Rectal cancer
• Vaginal cancer
• Uterine cancer

15. Squamous epithelial tumors
• Mimics of squamous precursor lesions
• Squamous metaplasia
• Atrophy of the uterine cervix
•Squamous cell tumors and precursors
• Condyloma acuminatum
• Squamous intraepithelial lesions of the uterine cervix
• Squamous cell carcinoma, HPV associated, of the uterine cervix
• Squamous cell carcinoma, HPV independent, of the uterine cervix
• Squamous cell carcinoma, NOS of the uterine cervix
Glandular tumors and precurs
• Benign glandular lesions
• Endocervical polyp
• Müllerian papilloma of the uterine cervix
• Nabothian cyst
• Tunnel clusters
• Microglandular hyperplasia
• Lobular endocervical glandular hyperplasia
• Diffuse laminar endocervical hyperplasia
• Mesonephric remnants and hyperplasia
• Arias Stella reaction of the uterine cervix
• Endocervicosis of the uterine cervix
• Tuboendometrioid metaplasia
• Ectopic prostate tissue
•Adenocarcinomas
• Adenocarcinoma in situ, HPV associated, of the uterine cervix
• Adenocarcinoma, HPV associated, of the uterine cervix
• Adenocarcinoma in situ, HPV independent, of the uterine cervix
• Adenocarcinoma, HPV independent, gastric type, of the uterine cervix
• Adenocarcinoma, HPV independent, clear cell type, of the uterine cervix
• Adenocarcinoma, HPV independent, mesonephric type, of the uterine cervix
• Other adenocarcinomas of the uterine cervix
•Other epithelial tumors
• Carcinosarcoma of the uterine cervix
• Adenosquamous and mucoepidermoid carcinomas of the uterine cervix
• Adenoid basal carcinoma of the uterine cervix
• Carcinoma of the uterine cervix, unclassifiable
•Mixed epithelial and mesenchymal tumors
• Adenomyoma of the uterine cervix
• Adenosarcoma of the uterine cervix
•Germ cell tumors
• Germ cell tumors of the uterine cervix
This classification is the updated classification of tumors of the
cervix as per the World Health Organization classification of
tumors of female reproductive organs, 5th edition (2020)

16. Major updates
Squamous lesions:
• Invasive squamous lesions are now classified in 2 main categories:
HPV associated and HPV independent
• HPV independent squamous cell carcinomas are rare but their
existence is now acknowledged as they may behave more
aggressively than the more common HPV associated lesions
Glandular lesions:
• Both preinvasive and invasive glandular lesions are now classified in 2
main categories: HPV associated and HPV independent
• HPV associated adenocarcinomas can be classified using terminology
from previous classification; however, they need to be distinguished,
as a group, from HPV independent tumors
• HPV independent adenocarcinomas are most frequently of the gastric
type (with both in situ and invasive forms)
• Other distinct types include clear cell and mesonephric carcinomas

17. Histopathology

23. Invasive well differentiated keratinizing squamous cell carcinoma: group of pleomorphic malignant cells, more or
less differentiated and with spindle cell shape. (obj. 40x)

24. Question:
According to the latest classification of female genital tumors from
the World Health Organization, which is currently a major category
in the classification of squamous cell lesions?
a) Basaloid carcinoma
b) Ectopic prostatic tissue
c) Keratinizing squamous cell carcinoma
d) Adenosquamous carcinoma
e) Squamous cell carcinoma, HPV associated

25. Answer:
e) Squamous cell carcinoma, HPV associated. Squamous cell
carcinoma of the uterine cervix is now classified as HPV
associated and HPV independent.
Basaloid and keratinizing are morphologic variants of squamous
cell carcinoma but do not represent diagnostic categories.
Ectopic prostatic tissue belongs to the category of benign
glandular lesions and
Adenosquamous carcinoma belongs to the category of mixed
epithelial tumors.

26. Thank You