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Cervical Malignancy and Pre-Malignancy. Valerie Capstick, 2010. Malignant Changes in the Female Cervix: Objectives. Describe the risk factors, symptoms, and physical finding characteristic of cervical cancer Describe the spread pattern of cervical cancer

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Malignant changes in the female cervix objectives
Malignant Changes in the Female Cervix: Objectives

  • Describe the risk factors, symptoms, and physical finding characteristic of cervical cancer

  • Describe the spread pattern of cervical cancer

  • Describe the types of treatment available for cervical cancer.


Premalignant changes in the female genitaltract objectives
Premalignant changes in the Female GenitalTract:Objectives

  • Describe the normal changes expected in a cervix as a woman matures.

  • Describe the patho-physiology of premalignant change.

  • Appropriately counsel and manage (make appropriate referral) a woman with an abnormal pap smear.

  • Demonstrate a knowledge of the behaviour of the HPV virus sufficient to reassure women with evidence of infection.

  • Offer and appropriately counsel on the use of the HPV vaccine.

  • Suspect Vulvar Cancer and/or Dysplasia (VIN) and biopsy/refer appropriately.


Pbl mrs woo
PBL: Mrs Woo

  • Main problem: Post menopausal bleeding

  • Findings: normal looking cervix (other than some blood on it)

  • Pap smear: HSIL.

  • Did any groups not get to this point?


Cancer of the uterine cervix

Cancer of the Uterine Cervix

Starting with the end.

Finishing with the prevention.


Cancer of cervix introduction
Cancer of Cervix: Introduction

  • 500,000 cases worldwide a year, making it the second most common cancer in women.

  • In Africa, Caribbean and Latin America- cervical cancer is the most common cause of cancer death



Some demographics about cancer of the cervix
Some demographics about Cancer of the Cervix

  • Average age 52, with peaks at 37 and 62

  • Incidence in Canada in 2009 (estimated)

    • 8.4/100,000 women

    • 1,300 new cases diagnosed in 2009 (Canada)

      • 1.6% of all cancers diagnosed in women (2009)

    • 380 deaths in 2009

      • 1.1% of all cancer deaths in women(2009)

    • In Alberta (estimated) for 2009

      • 160 new cases

      • 40 deaths


Cancer diagnosis in women in alberta 2009
Cancer Diagnosis in Women in Alberta -2009

  • Total: 7300

  • Breast 2000

  • Lung 850

  • Colorectal 780

  • Uterus 420

  • Ovary 180

  • Cervix 160


Cancer deaths women alberta 2009
Cancer Deaths, Women, Alberta, 2009

  • Total: 2,900

  • Breast 430

  • Lung 650

  • Colorectal 290

  • Uterus 70

  • Ovary 150

  • Cervix 40


Why do we devote a lecture to this
Why do we devote a lecture to this?

  • Less common diagnosis in Canada because we have a health system that screens for and treats the premalignant phase (HSIL).

  • Family Doctors, Nurse Practitioners and General Gynecologists are responsible for this.


Histology
Histology

  • Squamous carcinoma 80 %

    • Arises from the squamous epithelium of the cervix in the transformation zone

  • Adenocarcinoma ~ 15-20 %

    • Arises from the columnar epithelium of the cervical canal

  • Rare types

    • Small Cell Neuroendocrine (like small cell lung cancer) treated same way

    • Glassy cell carcinoma - subtype of adenosquamous carcinomas

    • Adenoma Malignum (minimal deviation adenocarcinoma)

    • Clear cell carcinoma-DES exposed

Don’t need to know the rare types


Patterns of spread
Patterns of Spread

  • Nodal

    • Stepwise progression

    • Obturator/internal iliac/common iliac/ paraaortic

  • Direct invasion

    • Rarely into bladder or rectum or up into uterus

    • Commonly laterally along parametrium (cardinal ligaments) and/or down vagina


Presentation
Presentation

  • Abnormal pap smear (but most abnormal smears are not cancer)

  • Abnormal vaginal bleeding

    • Intermenstrual

    • Postcoital

    • Postmenopausal

  • Vaginal Discharge, usually purulent

  • Pain-late symptom of advanced disease

  • Renal Failure- Bilateral ureteric obstruction-late symptom of advanced disease


Physical findings
Physical Findings

  • General physical exam including nodal sites

  • Bimanual exam

    • Hard and/or enlarged cervix (or normal)

    • rectovaginal exam to detect lateral spread into parametrium

  • On speculum exam

    • Normal exam often for women with abnormal pap

    • Fungating lesion

    • Ulcer


Investigations only some are allowed for stage assignment
Investigations (only some are allowed for stage assignment)

  • Chest X-ray

  • Cone biopsy (only in early or suspected cases)

  • Examination under Anaesthesia (optional)

  • Cystoscopy (bladder) and Sigmoidoscopy(optional)

  • CT scan of Abdomen and Pelvis To assess pelvic and paraaortic nodes, ureters and location of the kidneys (parametria)

  • MRI/PET


Stage 1 disease
Stage 1 disease

  • Stage 1

    • Primary disease is confined to the cervix

    • 1a1 - microinvasive (squamous only)

      • < 3 mm invasion, no vascular space involvement

      • Cone biopsy necessary for diagnosis (pathologic staging)

  • 1a2 - 3- 5 mm invasion

    • Cone biopsy necessary for diagnosis (pathologic staging)

  • 1b 1 - all lesions greater than 5 mm that are confined to the cervix and < 4 cm

  • 1b2- >4cm, confined to cervix


  • Stage 1a therapy
    Stage 1a Therapy

    • Ia1-nodes can be assumed to be negative- treatment based on reproductive situation. (cone or hysterectomy)

    • Ia2-nodes have a small chance of being positive- conservative (fertility sparing) surgery can be offered.

      • Eg. Large cone and pelvic nodes

      • Radical trachelectomy and nodes

      • Radical hysterectomy and nodes (some movement towards less radical hysterectomy in these women)


    Stage 1b therapy
    Stage 1b Therapy

    • 1b1(<4 cm)

      • Radical hysterectomy and node dissection

      • Radical radiotherapy+/- chemotherapy

    • 1b2

      • Almost always radical radiotherapy and chemotherapy


    Stage 2
    Stage 2

    • Cervical carcinoma invades beyond uterus, but not to pelvic wall or to the lower third of vagina

      IIa upper vagina with no parametrial invasion

      IIb Parametrial invasion

      THERAPY

      Most treated with Radiotherapy and chemotherapy

      Occasional IIa will get surgery


    Stage 3
    Stage 3

    • Tumor extends to the pelvic wall, and/or involves the lower third of the vagina, and/or causes hydronephrosis or nonfunctioning kidney

      • IIIa Tumor involves lower third of the vagina, no involvement of side wall

      • IIIb Tumor extends to pelvic wall, and/or causes hydronephrosis

        Treatment: radical radiotherapy and chemotherapy


    Stage iv
    Stage IV

    • Tumor invades mucosa of the bladder or rectum, and or extends beyond true pelvis

      • IVa invades bladder or rectum, and or extends beyond true pelvis (?)

        • treat: radical radiotherapy +/- surgery

      • IVb Distant Metastasis (eg. lung, axilla, supraclavicular)-does not include nodes in abdomen (because you need CT/MRI/PET to diagnose.

        • Treat: palliative radiotherapy, chemotherapy


    Carcinoma cervix factors influencing treatment options
    Carcinoma Cervix: Factors influencing treatment options

    • Stage: Stage 1b1 and less can be surgery

    • Ability to tolerate surgery:

      • Young and thin versus old and fat

    • Desire for Fertility

      • Stage 1 disease


    Radical hysterectomy stage 1b
    Radical Hysterectomy (stage 1b)

    • Radical hysterectomy and pelvic node dissection:

      • Ovaries can be spared.

      • Cure rates high (90-95 %)

      • If positive nodes are found (10% of patients) then postoperative radiation and chemotherapy is given to the pelvis.

      • Laparotomy or Laparoscopy (regular or robotic assisted)


    Radical hysterectomy
    Radical Hysterectomy

    • Ovaries can be spared

    • Remove

      • Cervix

      • Uterus

      • Upper vagina

      • Paracervical tissue (we call it Parametrium)


    Radical hysterectomy1
    Radical Hysterectomy

    • Cancer

    • Parametrium

    • Vaginal cuff

      • (Posterior only, in this picture, to show cervical lesion)


    Fertility preservation
    Fertility Preservation

    • Radical Trachelectomy (removal cervix) and pelvic node dissection ( lesions up to 2 cm)

    • Or

    • Cone Biopsy and node dissection

      • Lesion already removed with LEEP/cone with negative margins.


    Radical radiotherapy for cancer of the uterine cervix
    Radical Radiotherapy for Cancer of the Uterine Cervix

    • As primary treatment, with Cisplatin chemotherapy weekly

      • Intracavitary (brachytherapy) 1 or 2 treatments

      • External beam- 4500-5000 CGy over approx 25 fractions (five weeks)

    • Post operative for positive nodes or high risk features (ie. Close margins)


    Radiotherapy for cervical cancer benefits
    Radiotherapy for cervical cancerBenefits

    • Almost any age/health/stage

    • Potential for cure for any patient with disease confined to pelvis


    Radiotherapy risks
    Radiotherapy-risks

    • Acute: cystitis, diarrhea, pubic hair loss

    • Chronic:

      • ovarian failure,

      • vaginal stenosis,

      • Radiation cystitis, proctitis

      • Fistulas(rare)

      • Small bowel obstruction


    Survival at 5 years
    Survival at 5 years

    • Microinvasive 100%

    • Stage 1b 85-90 %

    • Stage 2 50%-75%

    • Stage 3 30 %-50%

    • Stage 4 10%


    Recurrence progression surgical salvage
    Recurrence/Progression Surgical Salvage

    • The only salvage for recurrent or persistent disease after radical radiotherapy is surgery ( 1-2 a year in northern Alberta)

    • Pelvic Exenteration 50 -60% cure rates

      • Removal of the uterus, cervix, and vagina , and bladder and often the rectum.

      • Urinary diversion ( pouch or ileal conduit)

      • Colostomy or reanastomosis of the bowel

      • Optional reconstruction of the vagina



    Premalignant changes of the uterine cervix

    Premalignant changes of the Uterine Cervix

    And how we prevent Cervical Cancer.


    Pathophysiology of premalignant changes on cervix

    Pathophysiology of Premalignant changes on cervix

    Two types of epithelium on the cervix interact to create an area that is vulnerable to the oncogenic HPV virus. The penis does not have this type of interaction


    The cervix at colposcopy
    The cervix ( at colposcopy)

    Squamous

    Columnar (produces mucous)

    Squamocolumnar

    Junction (SCJ)

    What is metaplasia?

    NOTE: This cervix has

    had acetic acid applied,

    the SCJ is not obvious

    with the naked eye or

    with out acetic acid.


    Metaplasia
    Metaplasia

    Normal Process !!

    Conversion of a normal glandular epithelium to a normal squamous epithelium

    Starts at puberty, accelerates at pregnancy

    These cells are uniquely vulnerable to HPV infection.


    METAPLASIA

    (everyone)

    ONCOGENIC STIMULUS

    (Human papillomavirus infection)

    (80% of ever sexually active females)

    DYSPLASIA

    (Cervical Intraepithelial Neoplasia)

    (1-3% of those infected with HPV)

    INVASIVE CARCINOMA

    (?% Of those with dysplasia who do not get diagnosed and treated)


    Colposcopy pap smear showed precancerous change hsil
    Colposcopy :Pap smear showed Precancerous Change (HSIL)

    • HSIL arising at the squamocolumnar junction apparent one minute after application of acetic acid.

    • Cervix looked normal prior to acetic acid.


    invasive

    HSIL high grade

    Intraepithelial lesion

    Normal

    LSIL low grade

    Intraepithelial lesion


    Human papilloma virus

    Human Papilloma Virus

    ‘Persistent infection with one of the carcinogenic types of HPV is a necessary, but not sufficient, cause of both squamous and glandular malignancy.’


    Hpv warts asymptomatic infections precancer and cancer
    HPV-warts, asymptomatic infections, precancer and cancer

    • More than 45 types of HPV are transmitted by intimate sexual contact.

    • 80% of ever sexually active women are infected with HPV (lifetime)

    • Most HPV infections resolve spontaneously


    • Persistent infection with a carcinogenic HPV type is necessary for precancer and cancer to develop.

    • When the virus is not cleared, persistent carcinogenic HPV infection may cause precancerous tissue changes that can, over many years, progress to invasive cervical cancer.

    • Early detection and treatment during the lengthy precancerous stage can prevent the vast majority of cervical cancer.


    Pap smears

    Pap Smears necessary for precancer and cancer to develop.

    Technique described on one of the documents on HOMER

    (Technique for obtaining satisfactory pap smears)


    Pap smear technique summary
    Pap smear technique summary necessary for precancer and cancer to develop.

    • Need to sample the junction between squamous and columnar cells (Squamocolumnar junction) and the transformation zone(where metaplasia is happening)

    • Use spatula and cytobrush

    • Alberta is moving to a liquid based cytology system


    Pap smears what age to start how often when to stop any exceptions

    Pap smears necessary for precancer and cancer to develop.What age to start, how often, when to stop, any exceptions?

    See:

    Guideline for Screening for Cervical Cancer (on Homer)


    Summary of guidelines new in 2009
    Summary of guidelines:New in 2009 necessary for precancer and cancer to develop.

    • Start: age 21 or 3 years after first intimate sexual activity -whichever is later.

    • If three negative paps in first 3-5 years, then can do every 3 years.

    • By age 69, if no previous abnormalities, okay to stop doing paps.

    • High risk women (HIV, immunocompromised) should have annual paps.

    • Any woman with a past history of precancer or cancer should have annual paps.


    Abnormal pap smear

    Abnormal Pap Smear necessary for precancer and cancer to develop.

    Pathologist or cytotechnician create the report.

    Bad news: Many ways a pap can be abnormal, and type of change and age of woman dictates next step.

    Good news: The pathologist will tell you what to do as part of the report.


    Pap Smears: necessary for precancer and cancer to develop.A. Normal Pap, B. ASCUS (not normal, not precancerous…atypical squam cells undet. Significance)C. LSIL-low grade C. HSIL – high grade

    A

    B

    C

    D

    Redo pap if you get ASCUS


    Pap results see management of abnormal cytology in clinical practice guidelines

    Squamous necessary for precancer and cancer to develop.

    Normal (vast majority)

    ASCUS

    ASC-H (atyp squam, high grade)

    LSIL

    HSIL

    Invasive Carcinoma

    Glandular

    Normal (vast majority)

    AGC-(atypical glandular cells)

    Adenocarcinoma-in-situ

    Endometrial cells

    Adenocarcinoma

    Pap results-see Management of Abnormal cytology in Clinical Practice Guidelines.

    • Essentially, you either 1. Continue routine screening,

    • repeat pap earlier – ascus, and LSIL,

    • Refer for colposcopy- ASC-H, HSIL, AGC, adenoca-insitu

    • Call Gyne Oncologist – Invasive Carcinoma


    Colposcopy
    Colposcopy necessary for precancer and cancer to develop.

    • Investigation of abnormal paps

      • inspection of cervix under magnification and biopsy of the cervix

      • Treat any precancerous changes found at colposcopy, thus preventing cancer

      • Occasionally, at colposcopy, a true cancer is detected.


    Colposcopy1
    Colposcopy necessary for precancer and cancer to develop.

    • Magnification 8-10 X

    • Apply Acetic acid (vinegar)

    • Look at transformation zone:

      Areas of mosaic, punctation, white

      epithelium suggest areas of dysplasia.

      Biopsy suspicous areas (small, representative sample)


    Treatment
    TREATMENT necessary for precancer and cancer to develop.

    Must treat entire transformation zone:

    LEEP (loop electrosurgical excision procedure)-most common

    Hysterectomy-rare, usually only if other indications


    Colposcopy not satisfactory
    Colposcopy not satisfactory! necessary for precancer and cancer to develop.

    • Means that examiner was not confident that only precancer present.

    • Or Adeno ca in situ diagnosed

    • Cone biopsy is surgical removal (with a scalpal) of a wedge of the cervix


    Cone biopsy
    Cone biopsy necessary for precancer and cancer to develop.

    urethra

    Tenaculum on

    anterior lip of

    the cervix

    Specimen

    Weighted

    speculum


    Outcomes of treatment for premalignant changes on cervix
    Outcomes of treatment for Premalignant changes on cervix necessary for precancer and cancer to develop.

    • Aim is to preserve fertility

    • Small increase in incidence of cervical incompetence (dilates in pregnancy with out labor)

    • Small increase in incidence of cervical stenosis (cervix won’t dilate)

    • After one year followup, chance of HSIL again, down the road is same as general population


    Precancer of the vagina
    Precancer of the Vagina necessary for precancer and cancer to develop.

    • A very large area of cervical precancer can involve the vagina.

    • Recognized at colposcopy for abnormal pap

    • Also can get separate(not contiguous with cervix) patches on the vagina

    • Usually treated with laser

    • More difficult to eradicate, therefore longer followup and frequently need multiple treatments.

    • Undetected can lead to cancer of the vagina


    Premalignant change of the vulva
    Premalignant change of the vulva necessary for precancer and cancer to develop.

    • Called VIN (Vulvar intraepithelial Neoplasia)

    • Can become true invasive carcinoma vulva if not diagnosed.

    • Symptoms: burning, itching, lump, bleeding (cancer)

    • Must BIOPSY


    Take home messages
    Take home messages necessary for precancer and cancer to develop.

    • Most significant risk factor for cervical cancer: not having pap smears.

    • Having HPV, premalignant changes or cancer of the cervix does not make a woman promiscuous. (hate that term)


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