Cervical Cancer Screening

Etiology

Screening Guidelines
Review changing guidelines and reason for change Reporting of results: Bethesda 2001 guidelines Treatment Assess knowledge

Why Screen for Cervical Cancer?

3rd most common gynecological cancer in the US. Approx 11,000 new cases diagnosed yearly in US

High mortality if not diagnosed, and better prognosis with less disease extent
Asymptomatic stage can last 10-20 years Test is inexpensive, Cumulative sensitivity of PAP smear over 10 years is sufficient. 50% of invasive cervical carcinoma in US occur in women who never had a Pap smear

Historic data from British Columbia: 80% decline in cervical cancer mortality between 1955 and 1988

Risk Factors for Cervical Cancer

Chronic infection with high risk HPV: 16,18,45,31,33,52,58 and 35 are responsible for 95% cervical cancers and two ( types 16 and 18) are responsible for 70 % of cervical cancer HPV is the most common STD in US; 75% of people are infected at some time in their lifetime. In most cases it is transient and is cleared by an appropriate immune response usually within 2 years. History of multiple sexual partners HIV (OR 4-6) Immunosuppressive therapy for transplant or other reasons Cigarette smoking increases the risk of cervical cancer four fold Exposure to a sexually transmitted disease such as Chlamydia with high risk HPV increases risk of progression of cervical dysplasia Long-term oral contraceptives (OR 2-4) Exposure to DES

Human Papillomavirus (HPV)

Thought to be responsible for 5% of all types of cancers worldwide
100% of cervical cancers 90% of anal cancers 40% of penile, vaginal, and vulvar cancers 25% of oral cavity cancers 35% of oropharyngeal cancers

Normal cervix on colposcopy:

Abnormal Cervix on colposcopy

Cervical Cancer (invasive carcinoma)

Normal PAP smear

CIN 1

CIN 2

Normal to CIN 3 progression:

When Should We start Screening?

2009 ACOG recommendations: Screening should begin at age 21 irrespective of the age of onset of sexual experience Rationale: cervical cancer is very rare in women age 21 and younger Most cytological abnormalities in adolescents and younger women spontaneously regress and waiting until age 21 avoids unnecessary and harmful procedures

Frequency of Screening:
Every 2 years for women age 20-29. Women 30+ with 3 consecutive normal PAP smears can extend to 3-year intervals (ACOG)
Rationale for change: potential for spontaneous regression of dysplasia and slow progression of cervical cancer/ease of detection and treatment of premalignant stages

If 3 consecutive normal PAP smears, extend to 3-year intervals at physicians discretion based on patient risk factors (USPSTF) Every 1-2 years before age 30; every 3 years after 30, if 3 consecutive normal PAP smears (ACS)

When to Stop Screening?

ACOG Screening may be discontinued at age 65-70 with at least 3 or more negative consecutive PAP smears and no abnormal PAP smears in last 10 years USPSTF Discontinue at age 65 with adequate recent screenings and not at risk for cervical cancer (requires continual reassessment). ACS Stop at 70 if 3 normal screening PAP smears and no abnormalities in last 10 years.

Exceptions:
unscreened or under screened women hysterectomy for high grade dysplasia (CIN2 and CIN3)/cervical cancer change in patients risk factors ( new sexual partners etc)

Screening PAP smears in patients with hysterectomy:

If hysterectomy is for a benign condition and patient lacks a cervical remnant, further PAP smears are not required. Continue with yearly PAP smears in patients with prior CIN 2 or CIN 3 or cervical cancer. Continue with PAP smears per screening protocol if reason for hysterectomy is unclear and pathology report is not available.

Exceptions to the rule for screening guidelines: Risk factors such as HIV, immunosuppression (e.g. following solid organ transplant): screen twice a year following the diagnosis and then annually thereafter DES exposure in utero: annual PAP smears Women treated in the past for CIN 2 or CIN 3 or cervical cancer should continue with annual screening for at least 20 years thereafter. Patient under surveillance: if recent PAPs are abnormal: surveillance for 2 years or typically until 3 subsequent consecutive PAP smears obtained 6 months apart are negative.

Special circumstances:
* Homosexual patients: HPV infection is spread from one
woman to another during sexual contact. Lesbians should undergo cervical screening as per protocol for all other women Reliable history of no vaginal intercourse or non penetrating sexual contact ever in their life time: it may be appropriate to delay initiating cervical cancer screening

Women who have been immunized against HPV-16 and HPV-18 should be screened by the same regimen as non-immunized women.

Reporting by the Bethesda System:

1. Specimen Adequacy
a. Satisfactory for evaluation b. Processed and examined, but unsatisfactory for evaluation because of.

2. Descriptive diagnosis
3. General Categories
a. Negative for intraepithelial lesion or malignancy

b. Epithelial cell abnormality-glandular or squamous

c. Other

Inadequate Specimen:
Unsatisfactory for interpretation or Satisfactory for interpretation, no ECC cells or TZ elements identified or partially obscured by blood or mucus and may not be satisfactory for interpretation
Repeat in 12 months if normal exam + no risk factors OR Repeat in 6 months if previous squamous cell abnormality, HPV high risk subtype positive in last 12 months, cant see entire cervix, abnormal examination, immunosuppression, or history of insufficient screening in the past

Other information in the PAP:

Candida infection Trichomonas (treat) Actinomyces infection Changes seen with HSV Shift in vaginal flora Inflammation IUD Atrophy Endometrial cells in women >40 (investigate for endometrial cancer)

Reactive changes:

Squamous cell abnormalities:

(7% of women receiving PAP smears
each year)

ASC-US (includes ASC-H)

(2-3 million, 3% of PAP smears)

LGSIL (1.25 million)

HGSIL (300,000)
Squamous cell carcinoma (12,800)

Cervical Dysplasia Terminology:

Cytology
ASC-US Atypical squamous cells of undetermined significance Atypical squamous cells, cannot exclude high grade SIL Low-grade squamous intraepithelial lesion

Histology
atypia or metaplasia

ASCH

Varies!

LSIL or LGSIL

Cervical Intraepithelial Neoplasia CIN 1 = mild dysplasia CIN 2 = moderate dysplasia CIN 3 = severe dysplasia

HSIL or HGSIL

High-grade squamous intraepithelial lesion

AGC

Atypical glandular cells

Glandular atypia :

ASC-US and ASC-H:

Bethesda 2001 Changes

Atypical Squamous Cells (ASC) is now divided into 2 categories:

1. ASC-US: atypical squamous cells of undetermined significance- needs more evaluation/testing 2. ASC-H: atypical cells cannot exclude HSIL
- Contains features suggestive of HSIL - 5-15% of ASC cases

- High rates of progression

- Refer for colposcopy

MANAGEMENT OF ABNORMAL PAP SMEARS:

Management of ASC-US:
1. Triage with HPV testing:
If high risk HPV+, refer for colposcopy If high risk HPV negative, repeat PAP smear in one year

2. Repeat Pap:
Repeat Pap in 6 and 12 months If either is ASC-US or worse, refer for colposcopy

Management of ASC-H
Risk of dysplasia is 70-89% Risk of CIN 2 or worse is 50% HPV triage is not indicated Refer for colposcopy

Management of LGSIL/HGSIL
LGSIL: 15-30% risk of high grade CIN (CIN 2 or CIN 3):refer for colposcopy No role for HPV testing Exception: postmenopausal women with LGSIL can be triaged with HPV; manage the same as ASCUS

Glandular Cell Abnormalities

Atypical Glandular Cells (AGC):
More likely to be associated with both squamous and glandular abnormalities than ASCUS High rates of actual cancer diagnosis with this abnormality Pap smears are less sensitive for detecting glandular dysplasia and malignancy Refer for colposcopy and do endometrial biopsy

Summary:

Who Needs Referral for Colposcopy?

ASC-US with HPV+ ASC-US x 2 if no reflex HPV test ASC-H LGSIL (if postmenopausal, HPV screening may
be useful)

HGSIL AGC
Also need endometrial biopsy
American Society for Colposcopy and Cervical Pathology Guidelines

When is HPV Screening Useful?

HPV testing has higher sensitivity / lower specificity than Pap with less variability 1. Can stratify women with ASC-US 2. After colposcopy, if CIN 1 and prior cytology diagnosis of ASC-US, ASC-H, LSIL or atypical glandular cells, repeat HPV testing in one year to check for persistent HPV infection 3. Can stratify postmenopausal women with LGSIL 4. Follow up after treatment for CIN 2 and CIN 3 5. Adjunct to cytology for primary screening in women >30 years

HPV Screening Use:

Pap and HPV co-testing: sensitivity 100%
Can be used for women age >30 in combination with PAP smear (ACOG and ACS recommendations) every 3 years If negative for HPV and normal PAP smear, women >30 at very low risk to develop CIN2 or CIN3 in 3 years (<0.1%) Incidence of HPV in age >30 is half that of ages 24-29
If PAP smear is negative and high risk HPV+: repeat both tests in one year (not sooner)

HPV Screen Not Useful:

Adolescents women under age 30 Prescreening for HPV vaccination >21 years of age with ASC-H, LGSIL, HGSIL (refer to colposcopy regardless of HPV status) STD screening