Updates on Cervical Screening, Mammograms, and HPV

Darren Adams, D.O., FACOOG

June 4, 2010

Primary Care Symposium

Conflicts of interest

• I do not own stock, lecture or act as a paid spokesman for any company.

Objectives

• 1. Review Mammogram Controversies and recommendations.

• 2. Review ACOG Cervical screening recommendations.

• 3. Discuss HPV vaccination guidelines.

Mammograms

• The USPTF is comprised of an independent panel of experts in Primary care and prevention

• No new trials performed, reviewed data that has been available for years.

Mammograms

• The USPTF states that the risk reduction afforded by Mammography in the 39-49 and 50-59 age ranges is the same ~0.85/0.86

• However they state the Absolute risk in the 40’s is lower than other groups so potential harm may outweigh benefits

• 0.05 women could develop cancer 10-30 years from the small amount radiation exposure

Mammograms

• The recommendation to not screen in this age group reflects a value judgment both on the risks and benefits and acceptable cost

• These value judgments on risks and benefits based on a less than perfect screening modality

• There is no data about whether women would sacrifice years of life, for reduced anxiety of increased screening

Mammograms

• ACOG still recommends screening mammograms every 1-2 years in the 40-49 and annually after age 50

Mammograms

• HHS Secretary Kathleen Sebelius states that CMS would not be changing its mammogram coverage policy

Mammograms

• The USPSTF recommends against routine screening mammography in women aged 40 to 49 years. The decision to start regular, biennial screening mammography before the age of 50 years should be an individual one and take patient context into account, including the patient's values regarding specific benefits and harms. (grade C recommendation)

Mammograms

• The USPSTF recommends biennial screening mammography for women aged 50 to 74 years. (grade B recommendation)

• The USPSTF concludes that the current evidence is insufficient to assess the additional benefits and harms of screening mammography in women 75 years or older. (grade I statement)

Mammograms

• The USPSTF recommends against teaching breast self-examination (BSE). (grade D recommendation)

• The USPSTF concludes that the current evidence is insufficient to assess the additional benefits and harms of clinical breast examination (CBE) beyond screening mammography in women 40 years or older (grade I statement)

Mammograms

• The American College of Obstetricians and Gynecologists (ACOG) maintains its current advice that women in their 40s continue mammography screening every one to two years and women age 50 or older continue annual screening.

• Screening mammography every 1-2 years for women aged 40-49 years

Mammograms ACOG

• Screening mammography every year for women aged 50 years or older.

• BSE has the potential to detect palpable breast cancer and can be recommended.

• CBE every year for women aged 19 or older

Mammograms

• ACOG strongly supports shared decision making between doctor and patient, and in the case of screening for breast cancer, it is essential.

Breast Cancer Screening Recommendations

Organization/Nation Start Mammograms (age) Frequency (years)

USPSTF 50 2

AAFP 40 1-2

American Cancer Society 40 1

American College of Ob-Gyn 40 1-2

A College of Preventive Medicine 50 1-2

A College of Radiologists 40 1

World Health Organization 50 1-2

Hereditary Breast cancer

• Approximately 7% of breast cancer results from genetic mutations

• The majority (approximately 84%) of hereditary breast and ovarian cancer results from inherited mutations in two genes called BRCA1 (52%) and BRCA2 (32%).

• About 1 in 500 people carry a mutation in either the BRCA1 or the BRCA2 genes

• Generally, mutations in BRCA1 and BRCA2 are associated with a 45% to 87% risk of breast cancer by age 70

Hereditary Breast cancer

• The high survival rate of women diagnosed with early-stage breast cancer warrants heightened surveillance for women who carry mutations in BRCA1 and BRCA2

• Screening should commence at an earlier age in recognition of the early age of onset of hereditary breast cancer

• The National Comprehensive Cancer Network, recommends the initiation of clinical breast examinations, mammography, and MRI at age 25

Surveillance for Hereditary Breast Cancer

www.nccn.orgCancer 2004;100:479-89NEJM 2004;351:427-37

Procedure Age to begin FrequencyBreast self-exam 18 yrs Monthly

Clinical breast exam

25 yrs Twice a year

Mammography 25 yrs Yearly

MRI 25 yrs Yearly

“Red Flags” for Hereditary Breast and Ovarian Cancer Syndrome

• Breast cancer before age 50

• Ovarian cancer at any age

• Male breast cancer at any age

• Multiple primary cancers

• Ashkenazi Jewish ancestry

• Relatives of a BRCA mutation carrier Cancer 2005 Dec 15;104(12):2807-16

Science 2003;302:643-6American Society of Breast Surgeons, June 12, 2006

www.nccn.org

Cervical Screening

• The incidence of cervical cancer has decreased more than 50% in the past 30 years because of widespread screening with cervical cytology.

• The American Cancer Society estimates 11,270 new cases of cervical cancer in the United States in 2009, with 4,070 deaths from the disease

Cervical Screening

• Cervical cancer screening should begin at age 21 years

• The recommendation to start screening at age 21 years regardless of the age of onset of sexual intercourse is based in part on the very low incidence of cancer in younger women. It is also based on the potential for adverse effects associated with follow-up of young women with abnormal cytology screening results.

Cervical Screening

• In contrast to the high rate of infection with HPV in sexually active adolescents, invasive cervical cancer is very rare in women younger than age 21 years.

Cervical Screening

• Cervical cytology screening is recommended every 2 years for women aged 21–29 years, with either conventional or liquid-based cytology. Women aged 30 years and older who have had three consecutive cervical cytology test results that are negative for intraepithelial lesions and malignancy may be screened every 3 years.

Cervical Screening

• Certain risk factors have been associated with CIN in observational studies; women with any of the following risk factors may require more frequent cervical cytology screening: – Women who are infected with human

immunodeficiency virus (HIV) – Women who are immunosuppressed (such as those

who have received renal transplants) – Women who were exposed to diethylstilbestrol in

utero – Women previously treated for CIN 2, CIN 3, or cancer

Cervical Screening

• It has been demonstrated, however, that the rate of dysplasia decreases as the number of sequential negative Pap test results increases

Cervical Screening

• Formal cost-effective analysis of data from this national program showed that the most cost-effective strategy for cervical cancer screening is cytology testing no more often than every 3 years in women with prior normal screening test results

Cervical Screening

• It is important to educate patients about the nature of cervical cytology, its limitations, and the rationale for prolonging the screening interval beyond every year. In addition, regardless of the frequency of cervical cytology screening, physicians also should inform their patients that annual gynecologic examinations may still be appropriate even if cervical cytology is not performed at each visit.

Cervical Screening

• Because cervical cancer develops slowly and risk factors decrease with age, it is reasonable to discontinue cervical cancer screening at either 65 years of age or 70 years of age in women who have three or more negative cytology test results in a row and no abnormal test results in the past 10 years. If screening is discontinued, risk factors should be assessed during the annual examination to determine if reinitiating screening is appropriate

Cervical Screening

• Women who had high-grade cervical intraepithelial lesions before hysterectomy can develop recurrent intra-epithelial neoplasia or carcinoma at the vaginal cuff many years postoperatively

Cervical Screening

• Women who have had a hysterectomy with removal of the cervix and have a history of CIN 2 or CIN 3—or in whom a negative history cannot be documented—should continue to be screened even after their period of post treatment surveillance.

• Whereas the screening interval may then be extended, there are no good data to support or refute discontinuing screening in this population.

HPV

• More than 100 genotypes of HPV have been discovered

• 30 of these effect the genital tract, and 15 of these have been associated with cervical cancer

• 70 % of cervical cancer result from infection with HPV 16 and 18

• 90% of Genital wart are caused by 6 and 11

HPV

• Human papillomavirus causes carcinogenesis in the transformation zone of the cervix, where the process of squamous metaplasia replaces columnar with squamous epithelium

HPV

• Human papillomavirus infections are commonly acquired by young women shortly after the initiation of vaginal intercourse but, in most, they are cleared by the immune system within 1–2 years without producing neoplastic changes. The risk of neoplastic transformation increases in those women whose infections persist

HPV

• Since infection is sexually transmitted and is usually transient, the prevalence of HPV infections is highest among sexually active women in their 20s

HPV Clearance

HPV

• The majority of HPV infections are self-limited and spontaneously clear within a several-year period as a result of cell-mediated immunity

• By 23 months, more than 80% had cleared their HPV infections

HPV

• Although the clinical significance of HPV perinatal transmission is unknown, this route of transmission is well documented. A recent study of oral and genital HPV infections in infants born to both HPV-positive and HPV-negative women detected HPV DNA in 6% of the infants at birth, 13% at 6 weeks after birth, and 9% between 3 to 24 months of age

HPV

• There are 2 Vaccinations that are currently approved by the FDA:

• Gardasil

• Cervarix

HPV

• Testing for HPV is currently not recommended before vaccination

HPV

• Gardasil was approved for use in 2006

• Gardasil is a quadra valent inactivated vaccine that protects against Low Risk HPV 6 and 11 and High Risk 16 and 18.

• Gardasil is approved for both Females and Males form age 9-26

HPV

• Gardasil is a recombinant vaccine

• Best given prior to exposure to HPV

• 3 dose series– Now – 2 months after first dose– 6 months after first dose – No booster recommended

HPV

• Gardasil should not be given to those with Yeast Allergy

HPV

• Cervarix approved in 2009• Cervarix is a bivalent vaccine that protects

against High Risk HPV 16-18• 3 dose series

– Now – 2 months after first dose– 6 months after first dose – No booster recommended

HPV

• Cervarix should not be given to those with Latex allergy

HPV vaccination guidelines

Organization/Nation Start Vaccine Catch Up

ACIP 11-12 13-2 6

American College of Ob-Gyn 9-26

American Cancer Society 11-18None

World Health Organization 9-13

HPV

• Vaccination of immunosuppressed patients is not contraindicated, yet they may not mount a robust response

• Males can be vaccinated with Gardasil but not Cervarix at this time

Future ?

• Anal Pap smears– 4000 cases of anal cancer in women in 2003

and in contrast to cervical cancer the rates are increasing

Objectives

• 1. Review Mammogram Controversies and recommendations.

• 2. Review ACOG Cervical screening recommendations.

• 3. Discuss HPV vaccination guidelines.

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