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Cervical Disease and Neoplasms. Maria Horvat, MD, FACOG. Cervical Disease – Risk factors. HPV Smoking – 2 fold increase Young age at 1 st coitus Multiple sexual partners A partner with multiple sexual partners High parity Lower socioeconomic status Young age at 1 st pregnancy.

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Cervical disease and neoplasms

Cervical Disease and Neoplasms

Maria Horvat, MD, FACOG


Cervical disease risk factors
Cervical Disease – Risk factors

  • HPV

  • Smoking – 2 fold increase

  • Young age at 1st coitus

  • Multiple sexual partners

  • A partner with multiple sexual partners

  • High parity

  • Lower socioeconomic status

  • Young age at 1st pregnancy



Cervical disease
Cervical Disease

  • HPV associated with 99.7% of all cervical cancer

  • HPV types associated with higher oncogenic risk:

    • 16, 18

    • 31, 33, 35

    • 45

    • 51, 56



HPV

  • Obligatory intra-nuclear virus

  • Most remit spontaneously

  • 5% of infected women have persistent infection


Pap test
PAP test

  • Only a screening test

  • Goal:

    • To prevent cervical cancer


Histology of sil squamous intraepithelial lesions
Histology of (SIL) squamous intraepithelial lesions.

Grade 1 = CIN 1; Grade 2 = CIN 2; Grade 3 = CIN 3



Potential co factors in cervical carcinogenesis
Potential Co-Factors in Cervical Carcinogenesis

  • Other infectious agents

    • Herpes

    • Chlamydia

    • HIV and other immunosuppression

  • Diet

  • Smoking

  • Hormonal contraceptives

    • Weak immunomodulatory effect

    • Eversion of columnar epithelium

    • Decrease in blood folate levels

    • Progesterone effect on HPV


Management of adolescent women 18 yrs with histological diagnosis of cin grade 1
Management of Adolescent Women (<18 yrs) with histological diagnosis of CIN – Grade 1

< 18 yrs old with CIN 1

Repeat Cytology at 12 mos

< HSIL > HSIL

Repeat Cytology at 12 mos

Negative > ASC Colposcopy

Routine Screening


Management of adolescent women 18 yrs with histological diagnosis of cin grade 2 3
Management of Adolescent women (<18 yrs) with histological diagnosis of CIN – grade 2,3

<18 yrs old with CIN 2,3

Either treatment or observation is acceptable, provided colposcopy is satisfactory.

When CIN 2 is specified, observation is preferred. When CIN 3 is specified, or colposcopy is unsatisfactory, treatment is recommended.

Observation OR Treatment

With colposcopy and cytology with excision or

at 6 mos intervals for 24 mos ablation of T-zone

2x negative cytology colposcopy worsens or

And normal colpo. High-grade cytology or

colpo. Persists for 1 yr.

Routine Screening Repeat Biopsy CIN 3, or CIN 2 that persists

Recommended for 24 mos since initial dx


Management of women with atypical squamous cells cannot exclude high grade sil asc h
Management of Women with diagnosis of CIN – grade 2,3Atypical Squamous Cells: Cannot exclude high grade SIL (ASC – H)

>20 yrs old with ASC-H

Coloposcopic Examination


Management of women with atypical squamous cells of undetermined significance asc us
Management of Women with Atypical Squamous cells of undetermined significance - ASC-US

>20 yrs old with ASC-US

Repeat Cytology HPV DNA testing

@ 4-6 mos

Negative >ASC Positive Negative

(for high risk type)

Repeat

@ 4-6 mos Colposcopy Repeat cytol.

@ 12 mos


Naming
Naming undetermined significance - ASC-US


Cervical intraepithelial neoplasia
Cervical Intraepithelial Neoplasia undetermined significance - ASC-US


Colposcopic grading
Colposcopic Grading undetermined significance - ASC-US


Summary for the non gynecologist
Summary for the non-gynecologist undetermined significance - ASC-US

ASCUS

Negative HPV type Positive

Repeat Pap Refer for

in 6 mos coloposcopy


Cin 1 mild dysplasia
CIN 1 – mild dysplasia undetermined significance - ASC-US

< 18 yrs old >18 yrs old

Repeat Pap Colposcopy


Cin 2 3
CIN 2,3 undetermined significance - ASC-US

Colposcopy


Confirmed cin 2 3
Confirmed CIN 2,3 undetermined significance - ASC-US

Excision

(adolescents may perform colposcopy q 6 mos up to 24 mos)


Interventional techniques excisional
Interventional Techniques - Excisional undetermined significance - ASC-US

  • Conization

    • Cone of tissue is excised for further examination and/or to remove a lesion

    • Tissue is usually stained with iodine to demarcate the area of resection

    • Cold knife

    • Laser

  • LEEP

    • Loop electrosurgical excision procedure

    • May be complicated by burn artifacts

  • Ablative

    • Cryotherapy

      • Use of a probe containing carbon dioxide or nitrous oxide to freeze the entire transformation zone and area or the lesion

    • Laser vaporization therapy


Atypical glandular cells
Atypical Glandular Cells undetermined significance - ASC-US

AGUS

Colposcopy

ECC

Endometrial Sample, women >35 yrs


What is colposcopy
What is colposcopy? undetermined significance - ASC-US


Cervical cancer staging review
Cervical Cancer – staging review undetermined significance - ASC-US

  • Stage 0: CIS, CIN grade III

  • Stage 1: carcinoma strictly confined to the cervix

  • Stage 2: cervical carcinoma invades beyond the uterus, but not to the pelvic wall or to the lower third of the vagina

  • Stage 3: carcinoma has extended to the pelvic wall. On rectal exam there is no cancer-free space between the tumor and the pelvic wall. The tumor involves the lower 1/3 of the vagina. All cases with hydronephrosis or non-functioning kidney unless known to be due to other causes.

  • Stage 4: Carcinoma has extended beyond the true pelvis, or has involved the mucosa of the bladder or rectum.


Cervical cancer staging
Cervical Cancer Staging undetermined significance - ASC-US

  • Stage 0: The cancer cells are very superficial (only affecting the surface) are found only in the layer of cells lining the cervix, and they have not grown into (invaded) deeper tissues of the cervix. This stage is also called carcinoma in situ (CIS) or cervical intraepithelial neoplasis (CIN) grade III.


Cervical cancer staging1
Cervical Cancer Staging undetermined significance - ASC-US

  • Stage I: In this stage the cancer has invaded the cervix, but it has not spread anywhere else.

  • Stage IA: This is the earliest form of stage I. There is a very small amount of cancer, and it can be seen only under a microscope.

  • Stage IA1: The area of invasion is less than 3 mm (about 1/8-inch) deep and less than 7 mm (about 1/4-inch) wide.

  • Stage IA2: The area of invasion is between 3 mm and 5 mm (about 1/5-inch) deep and less than 7 mm (about 1/4-inch) wide.

  • Stage IB: This stage includes Stage I cancers that can be seen without a microscope. This stage also includes cancers that can only be seen with a microscope if they have spread deeper than 5 mm (about 1/5 inch) into connective tissue of the cervix or are wider than 7 mm.

  • Stage IB1: The cancer can be seen but it is not larger than 4 cm (about 1 3/5 inches).

  • Stage IB2: The cancer can be seen and is larger than 4 cm


Cervical cancer staging2
Cervical Cancer Staging undetermined significance - ASC-US

  • Stage II: In this stage, the cancer has grown beyond the cervix and uterus, but hasn't spread to the walls of the pelvis or the lower part of the vagina.

  • Stage IIA: The cancer has not spread into the tissues next to the cervix (called the parametria). The cancer may have grown into the upper part of the vagina.

  • Stage IIB: The cancer has spread into the tissues next to the cervix


Cervical cancer staging3
Cervical Cancer Staging undetermined significance - ASC-US

  • Stage III: The cancer has spread to the lower part of the vagina or the pelvic wall. The cancer may be blocking the ureters (tubes that carry urine from the kidneys to the bladder).

  • Stage IIIA: The cancer has spread to the lower third of the vagina but not to the pelvic wall.

  • Stage IIIB: The cancer has grown into the pelvic wall. If the tumor has blocked the ureters (a condition called hydronephrosis) it is also a stage IIIB.


Cervical cancer staging4
Cervical Cancer Staging undetermined significance - ASC-US

  • Stage IV: This is the most advanced stage of cervical cancer. The cancer has spread to nearby organs or other parts of the body.

  • Stage IVA: The cancer has spread to the bladder or rectum, which are organs close to the cervix.

  • Stage IVB: The cancer has spread to distant organs beyond the pelvic area, such as the lungs.


Question 1
Question #1. undetermined significance - ASC-US

  • What if HGSIL pap and normal colposcopy?


Answer 1
Answer #1. undetermined significance - ASC-US

  • LEEP or cone biopsy.


Question 2
Question #2. undetermined significance - ASC-US

  • Biopsy on face cervix is normal and ECC is positive, what is the next step?


Answer 2
Answer #2. undetermined significance - ASC-US

  • LEEP or cone biopsy.


There is hope
There is hope! undetermined significance - ASC-US

  • Gardisil immunization guards against types 6, 11, 16, and 18.

  • Administer at 0, 2, and 6 months for females 9 years or older.


Hpv vaccine trials
HPV Vaccine Trials undetermined significance - ASC-US


Phase 2 trial of quadrivalent hpv vaccine conclusions
Phase 2 Trial of Quadrivalent HPV Vaccine: Conclusions undetermined significance - ASC-US

  • The vaccine was highly effective in reducing incidence of persistent HPV infection

  • Efficacy with regard to clinical disease associated with HPV types 6,11,16,18, was 100%

  • The vaccine was highly immunogenic, inducing high antibody titers to each HPV type

  • The vaccine was generally well tolerated


Do condoms help prevent
Do condoms help prevent? undetermined significance - ASC-US

  • YES!

  • 60% decrease in transmission

  • Does not eliminate risk.


Pap smear schedules
Pap smear schedules: undetermined significance - ASC-US

  • Many different recommendations

  • ACOG

  • APGO

  • ACS


Pap smear recommendations
Pap smear recommendations undetermined significance - ASC-US

  • 1st pap by age 21 or within 3 years of 1st coitus

  • Annually until the age of 30

  • Pap with HPV at age 30, then can perform every few years.


Pap smear recommendations1
Pap smear recommendations: undetermined significance - ASC-US

  • Post Menopausal

    • Some guidelines: No Pap

    • ACOG: q 3-5 years

  • Hysterectomized female:

    • If hysterectomy for benign reasons, then pap q 3-5 years

      • Yearly if:

        • Cervix present

        • History of abnormal paps

        • History of gyne cancer

        • History of DES exposure

        • History of cervical cancer

        • Smoking (increases chance of vaginal cancer)


References
References undetermined significance - ASC-US

  • APGO Educational Series on Women’s Health Issues: Advances in the Screening, Diagnosis, and Treatment of Cervical Disease

  • Review in Obstetrics and Gynecology, Vol. 1 No. 1 2008

  • American Society for Colposcopy and Cervical Pathology

  • Crosstalk; Preventing Cervical Cancer and Other Human Papillomavirus-related diseases


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