Practice English Speaking&Listening with: Cervical Cancer

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Today, we will be discussing

cervical cancer.

Learning objectives for today.

At the end of this talk,

the student will be

able to understand

common presentations

of cervical cancer;

describe the importance of HPV

and cervical cancer;

describe basic screening

for cervical cancer;

understand the basis

of cervical cancer staging;

describe the basic treatment

strategies;

and discuss prognosis and post

treatment issues.

An outline for today's talk.

We'll begin

with a patient vignette.

Our patient is a 36-year-old

gravida 4, para 3 013 who

presents to clinic with vaginal

bleeding.

Upon further questioning,

she reveals that her bleeding is

worse after having sex.

She uses condoms intermittently,

and her last exam was six years

ago at the birth

of her last child.

The clinical presentation

of cervical cancer

can be quite heterogeneous.

Most cervical cancer in the US

is asymptomatic at diagnosis

and is found on routine pap

screening.

However, some details are

useful to remember, and they are

highlighted

in the above vignette.

First, the fact that she does

not have regular care

is emphasized by her last exam

being six years ago.

She also has

post-coital bleeding, which

is a buzzword

for cervical disease.

Finally, she only intermittently

uses barrier contraception,

which increases her exposure

to HPV.

The rate of cervical cancer

is much higher in developing

nations as opposed to developed

nations.

This is attributed to lack

of screening programs, which

in the US

typically diagnose and treat

dysplastic changes of the cervix

before they develop

into a neoplastic process.

As we know, cervical cancer

is driven by HPV.

Therefore, risk factors are all

related to this.

Early onset of sexual activity,

multiple sexual partners,

and high-risk sexual activity

all lead to increased exposure

to HPV.

Immunosuppression can also take

many forms.

Rheumatic diseases, which

require chronic steroid use,

can suppress the immune system,

allowing HPV to take hold.

Additionally, transplant

patients are at higher risk

of developing cervical cancer

because

of their immunosuppression.

Finally, HIV patients

are at a dramatically increased

risk.

Specifically, patients

with low CD4 counts

and high viral loads

are not able to clear the HPV

virus

and are more likely to undergo

malignant transformation.

If HAART is unable to decrease

viral load

and improve CD4 counts,

then the risk of cervical cancer

decreases.

HIV patients also have much

higher risks of treatment

failure and recurrence.

They may be worthy of increased

screening.

Low socioeconomic status

is linked with lack of screening

and treatment

of dysplasia, which can lead

to development

of invasive disease.

Finally, tobacco use increases

the risk of cervical cancer

in a yet to be elucidated way.

Most likely, this leads

to suppression

of the immune response

against HPV-infected cells.

As mentioned before,

the presentation

of cervical cancer

can be quite variable.

Pre-invasive or minimally

invasive disease is generally

asymptomatic and detected

with screening pap smear.

More advanced disease can

present as post-coital bleeding.

This occurs because trauma

during intercourse

to the friable cervical cancer

causes bleeding.

Rarely, cervical cancer

can present

as a sudden, massive,

life-threatening bleed which

requires emergent treatment.

Finally, a large cervical mass

can become necrotic and present

with profuse, malodorous vaginal

discharge.

The development

of cervical cancer

is driven

by the human papillomavirus.

HPV is very common

and can be seen

in a large portion of sexually

active adults.

HPV is seen in greater than 99%

of cervical cancer specimens.

It is

prevalent in both squamous cell

carcinoma of the cervix as well

as adenocarcinoma.

There are over 100 subtypes

of HPV, but subtypes 16 and 18

are what drive cervical cancer

in the US.

Oncogenic transformation

generally occurs

in the transformation zone.

This area is the border

between the endo-

and ectocervix, where

the epithelium transitions

from squamous to columnar.

The location

of the transformation zone

is

dependent on the hormonal milieu

and changes over the course

of a woman's life.

Persistent HPV infection

in this area causes insertion

of the E6 and E7 oncogenes

into the epithelium

over an extended time.

The E6 oncogene inactivates p53,

and E7 inactivates pRb,

both of which

are tumor suppressor genes.

The latency period

for this process is extended,

and it generally takes 15 years

from first sexual contact

until development

of cervical cancer.

As you may have gathered,

the true key to cervical cancer

is prevention.

Cervical cancer screening

consists of regular pap smears.

Different professional societies

have different recommendations,

but ACOG recommends beginning

annual pap smears at age 21.

At age 30, in a low-risk patient

with three

consecutively normal pap smears,

screening can be spaced

to every two to three years.

Pap smears are analyzed using

cytology.

Cytology is graded based

on either squamous or glandular

abnormalities,

based on the Bethesda criteria.

Early changes can just

be followed with repeat pap

smear

at an appropriate interval,

whereas moderate or severe

changes are followed

with colposcopy

and directed cervical biopsies.

Colposcopy consists of examining

the cervix using a microscope

and using-- with acetic acid

stains.

Abnormal areas will appear

as leukoplakia,

acetowhite changes,

or abnormal vascular patterns

such as punctaicism

or mosaicism.

These areas

are

suspicious

for cervical dysplasia

and should be biopsied

if the entire transformation

zone is visualized

and the colposcopy is considered

adequate.

If colposcopy is inadequate,

an endocervical curettage can be

performed to evaluate

the endocervix.

Once cervical cancer has been

diagnosed, generally

with histology

from a cervical biopsy,

it must be staged.

Cervical cancer

is unique to gynecologic cancers

in that it is staged clinically.

This is driven by the fact

that cervical cancer is seen

at increased frequency

in low-resource settings

and staging should take this

into account.

Therefore, a detailed pelvic

examination is performed

to assess the cervix,

parametria, rectum, and lymph

nodes.

Often, this exam is performed

under anesthesia to allow

the practitioner to perform

the exam with a fully relaxed

patient.

Endoscopy consists of cystoscopy

and proctoscopy and are allowed

for use in staging to determine

if the tumor has invaded

into the bladder or rectum.

Finally, simple imaging,

including chest X-ray

and intravenous pyelogram

are used to assess for a lung

metastasis or ureteral

obstruction.

Many high-resource settings will

supplement or replace

these tests

with computed tomography,

with or without positron

emission tomography.

This allows

for further assessment of lymph

node status and tumor invasion,

which would change treatment

and prognosis but not staging.

Early stage disease is disease

that is limited to the cervix

and is less than four

centimeters in size.

If disease is pre-invasive,

then a simple hysterectomy

can be performed.

Disease limited to the cervix

and less than four centimeters

in size can be treated using

radical hysterectomy

with lymphadenectomy.

This consists

of end-block resection

of the cervix, uterus,

parametria, tubes,

and upper one-third

of the vagina.

The pelvic and periaortic lymph

nodes are also excised

to further define the extent

of disease.

If the patient is young

and future fertility is desired,

radical trachelectomy can be

considered, which consists

of end-block resection

of the cervix, parametria,

tubes, and upper one-third

of the vagina.

In this case, the corpus

of the uterus and the tubes

are left in place.

Finally, a patient may decline

surgery and instead undergo

definitive chemoradiation, which

consists

of daily pelvic radiation

with weekly cisplatin

for a total of usually five

weeks.

Advanced stage disease

is disease that has extended

past the cervix or greater

than four centimeters in size.

It can invade the lymph nodes,

bladder, rectum,

or extend beyond the pelvis.

Advanced stage disease

is treated

with definitive chemoradiation,

as it is beyond the stages

of surgical resection.

Additionally, advanced stage

disease may require placement

of percutaneous nephrostomy

tubes, if the ureters are

obstructed, or colostomy,

if the rectum is obstructed.

Prognosis is generally

dependent on spread.

Early stage disease that

is fully resected

leads to excellent prognosis.

For example, carcinoma in situ,

treated

with simple hysterectomy,

leads to survival rates

approaching 100%.

Stage 1B disease, the largest

disease

amenable to surgical resection,

is associated with an 85%

survival rate.

As stage increases, survival

drops precipitously.

More subtle prognostic factors

include nodal status,

with positive status portending

worsening survival;

lymphovascular space invasion,

which also decreases survival

by increasing metastasis risk;

and persistent HPV 18

at the surgical margins, which

leads to increased recurrence

risk.

In advanced cases, death usually

occurs from uremia, infection,

or hemorrhage.

Even though treatment

of early stage cervical cancer

can be quite successful,

close follow-up is required

to evaluate for disease

recurrence.

Recurrence, if it occurs,

is most likely to recur

at the surgical margins--

in this case, the vaginal cuff.

Therefore, a full physical exam,

with speculum and bimanual exam

to assess for recurrence,

should occur every three months

for the first two years,

and then every six months

until the patient is five years

away from treatment.

She should receive pap smears

of the vaginal cuff at least

yearly, with some providers

performing them more often.

There is no set imaging

guidelines, but imaging should

occur if there is any suspicion

of disease recurrence.

Finally, as patients survive

this disease,

post-treatment quality of life

is an issue.

Ovarian failure

is a common occurrence

after chemoradiation.

This early menopause can cause

distressing effects, including

vasomotor symptoms,

vaginal dryness, and irritation,

as well as increased

cardiovascular risk

and decreased bone mineral

density.

These symptoms should be treated

in order to maximize

the patient's quality of life.

With surgical management,

the ovaries are left in situ,

but there are still

psychosocial factors which can

decrease the quality

of patients' life.

Psychosocial factors relating

to having cancer

of the female organs

can cause sexual dysfunction,

which is exacerbated

by physical factors related

to radiation

or surgical changes.

In summary, cervical cancer

is decreasing in incidence

secondary to screening efforts.

HPV infection

is key to the development

of cervical cancer.

Staging is based primarily

on physical exam.

Treatment includes

surgical management

for early stage disease

and chemoradiation

for high stage disease.

And there are

significant post-treatment

quality of life issues.

Here are key references

for further reading.

The Description of Cervical Cancer