Warning signs of cervical cancer:

colposcopy of superficially invasive

and squamous cell carcinoma

Tri A. Dinh, MD
Mayo Clinic Florida
Department of Gynecology
Jacksonville, FL
Disclosures
• Tri A. Dinh, MD – Faculty – No disclosures

Images used with permission:

• Apgar B, Brotzman G, Spitzer M. Integrated Colposcopy: A Text and Atlas. Elsevier; 2002, 2008. (ABS)
• Ferris D, Cox T, O’Connor D, Wright C. Modern Colposcopy. Wolters Kluwer, ASCCP; 2002
• Personal collections as noted on slides
Objectives
• Review epidemiology of cervical cancer
• Recite warning signs of squamous cell carcinoma
• Review cytology and histology of cervical cancer
• Describe colposcopy of superficially invasive and
invasive cancer
Cervical cancer incidence and mortality
• Fourth most common cancer in individuals
worldwide
• 528,000 estimated new cases reported in 2012
• 85% of the global burden occurs in the less
developed regions, where cervical cancer
accounts for almost 12% of all cancers in females
• In US1
• Estimated 13,170 new cases
• 4,250 deaths
Apgar, Brotzman, Spitzer
• Ranks 15th in incidence and mortality
1American Cancer Society, Cancer Facts & Figures 2019. Atlanta: American Cancer Society; 2019.
Symptoms of cervical cancer
• Postmenopausal bleeding - 46%
• Abnormal uterine bleeding - 20%
• Postcoital bleeding - 10%
• Vaginal discharge - 9%
• Pain - 6%
Cervical Carcinoma

Apgar, Brotzman, Spitzer

Cytology of invasive disease
 Markedly
Cytology of atypical cells
invasive indicative of
malignancy
squamous
carcinoma
Accompanying
inflammatory
exudate and blood
obscures cytologic
findings
Terence Colgan, MD
Cytology of Necrotic cells in
invasive the background
squamous
Malignant cells,
carcinoma loss of cohesion
with associated
inflammatory
debris

Terence Colgan, MD
Histology of invasive disease
Histology of cervical cancer
Prevalence HPV (+)
Squamous 75% (falling) >95%
Adenocarcinoma 25% (rising) >95%
Endocervical >95%
Endometrioid 1-17%
Clear Cell <13%
Adenoid Cystic <3%

Rare types unlikely to have HPV association: Serous, Glassy Cell, Neuroendocrine (Large & Small Cell), Sarcoma, Lymphoma
 Histology of cervical cancer
Squamous carcinoma Adenocarcinoma
(endocervical)

From Woodruff JD, Parmley T

How cancer may be missed: pitfalls in
diagnosis
• Inexperienced colposcopist
• Taking too few biopsies
• Biopsies too small - no stroma
• Inadequate follow-up especially when cytology, colposcopy,
and histology don’t correlate
• Failure to perform endocervical sampling when indicated
• No excision when endocervical sampling positive for CIN 2,3
• Performing ablation without biopsy / endocervical sampling
Use all available information
• Presenting symptoms
• Colposcopic exam
• Presenting Pap
• Careful bimanual and rectovaginal exam
• Be gentle: cervix may be fragile
Be rigorous in search for cancer
• Look for cancer even if it’s not expected
• The most common cytology finding preceding a diagnosis of
cancer is ASC-US
• Beware of repeat inflammatory cytology with no
explanation
• Beware of consecutive unsatisfactory cytology
Why are warning signs important?

• CIN is usually colposcopically evident

• Early cervical cancer can be subtle
• Impressive CIN may distract from early signs of invasion
Colposcopic features of invasion
Warning Signs
• Color
• Acetowhite
• Leukoplakia
• Yellow-tan
• Atypical Vessels
• Contour
• Irregular
• Ulcer
• Exophytic lesion
Acetowhite, leukoplakia, yellow-tan

Apgar, Brotzman, Spitzer

Tan, gray - necrosis Dense white - keratosis Red - friable

M. Alvarez, C. Tedeschi, A
Waxman
CIN 3 or cancer?
• Large circumferential lesion
• Dense acetowhite
• Friable
• Peeling epithelium
• Lesion extends into canal

A Waxman, MD
CIN 3 or cancer?
• Peeling surface
• Coarse punctation
• Dense acetowhite extends
into canal

Manuel Alvarez, MD
Apgar, Brotzman, Spitzer
Be alert to the warning signs of cancer

• Large lesion
• Linear length > 10 mm
• Circumferential lesion
• Sharply-demarcated thick white lesion
• Lesion extending into canal
Be alert to lesions extending into the
endocervical canal
• Not fully visualized lesion or SCJ
• Positive endocervical sampling (high grade)
• Endocervical sampling usually cannot rule out invasion
since intact epithelium and stroma may not be present in the
sample
• Endocervical sampling with scant tissue and no diagnosis is
the same as no endocervical sampling
Apgar, Brotzman, Spitzer
Be alert to lesions extending into the
endocervical canal
• Don’t rely on negative
endocervical sampling if
cancer suspected
• Sensitivity of
endocervical sampling is
low (50%)
Endocervical sampling fragment
showed HSIL. Patient had cancer.

Photo: UNM Pathology

Apgar, Brotzman, Spitzer
Excision as treatment for CIN 2,3 may
uncover occult invasion
CIN 2 on ectocervix biopsy. Superficially
invasive found inside canal on loop excision.

A Waxman, MD
What should we do?
Biopsy, deep enough
to assess stroma

What shouldn’t we do?

Endocervical sampling
Excisional biopsy
Why?
Macroscopic cancer
is fragile! All that is
needed is confirmation
of invasion. Nothing more!
Apgar, Brotzman, Spitzer
Biopsy of suspected cancer

• Biopsy areas suspicious for cancer and CIN 2,3

• Biopsy areas of nodularity or ulceration
• Biopsy margin AND base of ulcer
• Biopsy areas with atypical vessels
• Biopsy areas of leukoplakia
• Biopsy must be at least 5mm to include underlying stroma
to assess invasion
Atypical vessels

Apgar, Brotzman, Spitzer

Atypical vessels
Spaghetti vessels

Hemorrhagic
dense white
surface

Apgar, Brotzman, Spitzer

• Thick, straight non-
branching vessels
• No acetowhite
• Biopsy!

Apgar, Brotzman, Spitzer

• Invasive cancer
• Post cone

• Dense acetowhite,
punctation above the
surface, atypical
vessels

Manuel Alvarez, MD
Apgar, Brotzman, Spitzer
• Straight, looping,
hairpin vessels

• Color - white and

orange

Candy Tedeschi, OGNP

• Exaggerated mosaic
pattern

• Mosaic vessels
becoming “atypical”

Apgar, Brotzman, Spitzer

 Atypical vessels

Coarse punctation raised

above surface
Manuel Alvarez, MD
Contour: ulceration or exophytic

Apgar, Brotzman, Spitzer

Clinical findings: invasive cervical
cancer
• Large, firm or barrel-shaped cervix
by palpation
• Neoplasia infiltrating into stroma
• Endophytic lesion
• Exophytic lesion
• Nodularity
• Ulceration
• Necrosis
• Atypical vessels
Apgar, Brotzman, Spitzer
Apgar, Brotzman, Spitzer
Acetowhite on posterior lip - superficial
ulceration - invasive cancer

Alan Waxman, MD
• Friable vessels – red
• Necrosis - gray, black
• Nodular lesion,
extensive necrosis -
invasive carcinoma

Candy Tedeschi, OGNP

Nodularity and ulceration
• Extensive lesion
• Ulceration
• Hyperkeratosis
• Nodularity
• Raised
• White to orange color
Apgar, Brotzman, Spitzer
 CIN 3 or cancer?
• Large lesion going into
canal
• Raised, irregular surface
• Peeling epithelium
• Atypical Vessels

Apgar, Brotzman, Spitzer

Apgar, Brotzman, Spitzer
When cytology, colposcopy and histology don’t correlate, Look further to rule out cancer
38-year-old with previous
CIN 3, no treatment or
follow-up for 5 years.
Now HSIL cytology.
Bx: superficially invasive
Apgar, Brotzman, Spitzer
Summary
• Most colposcopists will see very few cancers during
their career
• It is important to review colposcopic findings of cancer
on a regular basis
• CIN can frequently co-exist with overt carcinoma and
may produce impressive colposcopic findings that
distract attention from the more worrisome lesion