Presentation Notes: Note that these screening guidelines differ from the manufacturer’s package insert. Few absolute contraindications to intrauterine contraception use exist. The listed conditions are rated Category 4, according to the WHO Medical Eligibility Criteria for Contraceptive Use. Conditions assigned to Category 4 are those that represent an unacceptable health risk if the contraceptive method is used. For complete information about relative contraindications, see the WHO criteria, available at: http://www.who.int/reproductive-health/publications/mec.

Presentation Notes: Adolescents are typically considered poor candidates for IUDs because they may have a high risk of exposure to gonorrhea or chlamydia. A Canadian study of 28 patients ages 21 and under found that when candidates are properly selected and counseled, IUDs (in this case, the copper IUD) can be an appropriate and effective choice—especially for adolescents who have already had a pregnancy or failed or refused other contraceptive methods. Thirty-five percent of the patients discontinued IUD use an average of 13.4 months after insertion, most due to increased bleeding. Eight-five percent of users were somewhat satisfied, satisfied, or very satisfied with the method. The authors stated the LNG IUD also might be appropriate for some teens, because it may offer non-contraceptive benefits in the form of relief of menstrual cramping.

Presentation Notes: N/A

Presentation Notes:

Presentation Notes: Genital HPV infection is the most commonly diagnosed sexually transmitted infection in the United States, based on HPV DNA testing. [Trottier 2006], HPV is now known to be a necessary cause of cervical cancer. [Munoz 2006], Despite the fact that cervical cancer is highly preventable with screening and early intervention, about 13,000 new cases of cervical cancer occur annually in the U.S. [ASCCP Web site-premalignant: definition 2006], About 3,700 women die of the disease each year in the US. [American Cancer Society. Cancer Facts and Figures. 2006.], HPV also is associated with external genital warts and cancer of the penis, vagina, vulva, anus, and oropharynx. Gaps exist in screening—both in terms of women who receive no screening, infrequent screening or inadequate screening and in terms of false negative results with the Pap test. Most of the cases of invasive cervical cancer and death due to cervical cancer occur in women who did not receive proper screening. [Anhang 2004], Cervical screening has not been equally accessible to all women, and the incidence of cervical cancer is higher among ethnic minorities and poor women. [Anhang 2004], This presentation will address key HPV screening and management issues from a clinician’s perspective.

Presentation Notes: HPV has been associated with a number of human cancers. The virus is causative in cervical and anal cancer and a co-factor in other cancers.

Presentation Notes: HPV also is causative for external genital warts. In this presentation, we’ll focus on screening and prevention of cervical cancer and management of external genital warts, but will also provide an overview of the screening and prevention of anal cancer.

Presentation Notes: Virtually all cervical cancers are associated with persistent infection with high-risk HPV types. Data from a variety of studies (including case-control, prospective cohort series, and case series) have confirmed that certain HPV types are carcinogenic for the cervix: 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, others are probably carcinogenic, including: 26,53 66 68,73 82.

Presentation Notes: This slide shows the percentage of Pap tests showing ASC-US, LSIL or HSIL that are associated with HPV 16. Approximately 400,000 women have an ASC-US Pap annually associated with HPV 16. LSIL is less common than is ASC-US, but HPV infections are much more common in LSIL than ASC-US Paps—295,000 women each year are diagnosed in the United States with an HPV 16 associated LSIL Pap. About 182,100 HSIL are associated with HPV 16 annually. Combined, almost 900,000 women have an HPV 16 associated abnormal Pap smear each year in the United States. This is a huge burden of disease attributable to HPV 16.

Presentation Notes: In a literature review by Dunne and colleagues, 40 published studies on HPV prevalence in men were reviewed: Of these, 27 evaluated multiple specimens or sites, 10 evaluated a single site or specimen, and 3 evaluated risk factors or optimal anatomic sites/specimens for HPV detection, In the group of studies that evaluated multiple sites or specimens, the prevalence of HPV in men varied from 1.3% to 72.9%. Studies with immunocompromised persons were not included in this analysis.

Presentation Notes: N/A, Reference: Dunne EF, Nielson CM, Stone KM, Markowitz LE, Giuliano AR. Prevalence of HPV infection among men: A systematic review of the literature. J Infect Dis. 2006;194(8):1044-57.

Presentation Notes: Sexual intercourse is the primary route of HPV transmission. HPV is transmitted via direct genital contact (rather than via body fluids, like most STIs). [CDC. HPV Information for Clinicians], Receptive anal intercourse is strongly associated with HPV infection. [Burchell 2006], Genital contact in the absence of intercourse is a plausible means for HPV transmission, but the risk associated with this contact is much lower than that for intercourse. [Burchell 2006; CDC HPV Information for Clinicians], The virus also can be transmitted via oral-genital contact. Transmission is not thought to occur via inanimate objects, such as clothes. [CDC HPV Information for Clinicians], References: Centers for Disease Control and Prevention. Human Papillomavirus: HPV Information for Clinicians. November 2006. Available at: http://www.cdc.gov/std/HPV/hpv-clinicians-brochure.htm. Accessed March 20. 2007. Burchell AN, Winer RL, de Sanjose S, Franco EL. Epidemiology and transmission dynamics of genital HPV infection. Vaccine. 2006;24 (suppl 3):S3/52-S3/62.

Presentation Notes: Progression to precancer occurs when infection with HPV high risk types persists over time. Only small minority of women with HPV detectable by DNA assays have microscopic cervical abnormalities; however, at follow up 1 to 3 years later, 25% to 40% will have cervical abnormalities. [Moscicki 2006] These data point to the importance of persistence of HPV infection. In most cases, HPV infection—with low or high-risk types—is cleared by the body. Studies have shown that viral clearance is not often followed by subsequent infection with the same genotype. [Moscicki 2006] Less than half of women who develop HPV infection will have persistence of the same HPV type 12 months later. [Trottier 2006], Persistent infection is defined as detection of the same HPV genotype 2 or more times within a given interval of time; however, the duration of time defining persistence is not yet agreed upon. [Moscicki 2006], The HPV type affects both the likelihood of persistence and the risk of progression to precancer. HPV type 16 persists longer than other types and also is especially carcinogenic, with a risk of CIN-3 of 40% at 5 years. [Moscicki 2006], There are currently no data on the natural history of HPV infection in men. [CDC HPV Information for Clinicians]

Presentation Notes: More than 120 types of HPV have been identified. [De Villiers 2004; zur Hausen 2000], About 40 types can infect the genital tract. [Munoz 2006], Approximately 13 to 19 are considered high-risk types, meaning that persistent infection with these types is associated with an increased risk of cervical, anogenital, and other cancers (number considered high risk has varied in different studies). [De Villiers 2004; zur Hausen 2000; Munoz 2003], The most important high-risk types are 16 and 18. Type 16 alone causes half of all cases of cervical cancer. Type 18 causes another 20% of all cases. [Munoz 2003], In fact, persistent infection with high-risk HPV is responsible for 99.7% of cervical cancers. [Walboomers 1999], Low-risk HPV types, the most important of which are 6 and 11, are associated with external genital warts, or condylomata acuminata, and with low-grade cervical lesions. [Soper 2006]

Presentation Notes: This slide shows the relative frequency of detection of HPV types for specimens associated with cervical cancer. Notice that many of the lesions are associated with DNA from type 16 or 18 worldwide.

Presentation Notes: Persistent infection with high-risk types of HPV is necessary for the progression of high grade lesions to invasive cancer. [Trottier 2006]

Presentation Notes: Average episodes last 4-20 months [Trottier 2006], Most infections are cleared by the immune system. Only a small proportion of women with a particular HPV type test positive for the same type in subsequent testing [Trottier 2006], Most studies show that <50% of women are infected with the same HPV type 12 months later [Trottier 2006], Persistence of infection with HPV leads to abnormal clonal progression in the cervical epithelium and eventually may lead to invasive cervical carcinoma. [Moscicki 2006], Believed that carcinoma develops from infections that persist with continued viral replication within the squamous epithelium. [Trottier 2006], HPV type 16 infection tends to persist longer than infection with other HPV types. [Trottier 2006]

Presentation Notes: The risk of progression to invasive cervical cancer varies based on the degree of dysplasia, as measured by the cervical intraepithelial neoplasia (CIN) stage. CIN 1 = mild dysplasia, CIN 2 = moderate dysplasia, and CIN 3 = severe dysplasia, or carcinoma in situ. [ASCCP Web site-spectrum of disease 2006], Note that 60% of CIN 1 lesions will regress, compared with only 33% of CIN 3 lesions.

Presentation Notes: 90% caused by HPV types 6 and 11, Affects 1% of sexually active women age 18 to 45 in United States, CDC estimates 500,000 to 1 million cases annually, 240,000 initial office visits per year, 1% of sexually active US women age 18 to 45 affected, 1/3 of all STI dollars spent annually, Cost $167 million annually,

Presentation Notes: EGW can be diagnosed by visual appearance. Application of vinegar or acetic acid is not recommended. If necessary, diagnosis can be confirmed by biopsy. HPV tests are not indicated. (Picture is of extensive EGW in the perianal area).

Presentation Notes: This slides shows the Planned Parenthood Federation of America (PPFA) treatment algorithm for EGW. Note that ablative therapy, such as lasers, could be considered if lesions persist despite treatment.

Presentation Notes: The current approach to cervical cancer prevention: •Screen using cervical cytology in women of all ages according to published guidelines (cytology with or without HPV DNA testing), •Evaluate women with positive screening results using colposcopy and cervical biopsy, Treat women with biopsy-confirmed high-grade cervical cancer precursors, • [Speaker: Complete management and HPV DNA testing are covered in subsequent modules.]

Presentation Notes: ACS: Annual screening with conventional Pap test, Every 2 years for screening with liquid-based test, At age 30 if a woman has had 3 normal consecutive Pap tests, can change to every 2 to 3 years (but not if she has history of DES exposure or immunosuppression)

Presentation Notes: ACOG: Annually if <30 years old, At age 30 if 3 normal consecutive Pap tests, change to every 2 to 3 years (but not if she has history of DES exposure or immunosuppression), For women age 30 or older, either Pap or Pap plus HPV can be used for screening, At age 30 if HPV and Pap are both negative, change to no more frequently than every 3 years, USPSTF : Cervical cancer screening interval: at least every 3 years. The guidelines note that there is no direct evidence to support the clinical utility of more frequent screening.

Presentation Notes: ASC-US is the most common cytological abnormality in the United States—mean rate 4.7% in 2003. About 2.5 million cases of ASC-US are reported each year. The prevalence of CIN 2/3 among women with ASC-US is 7-12% in the U.S. Almost half of all cases of CIN 2/CIN 3 are diagnosed in women with ASC-US. Women with a cytological result of ASC-US require follow-up.

Presentation Notes: ASC-H is a designation given to specimens that show atypical squamous cells for which high-grade intraepithelial lesions (HSIL) cannot be excluded; specimens given this designation include both HSIL and mimics. It’s an uncommon finding, with a mean rate of just 0.43% in 2003. The risk of CIN 2/3 is higher for ASC-H than ASC-US (40% vs 15%). The prevalence of CIN2/3 among women with ASC-H ranges from 26% to 68%, It is important to consider the equivocal nature of this designation when making decisions about further evaluation. For example, clinicians should examine all of a patient’s pathology reports and colposcopy findings prior to making a recommendation about excision procedures.

Presentation Notes: LSIL is a common cytology abnormality that usually represents self-limited HPV infection, It is found more commonly in liquid-based cytology specimens than in conventional Pap specimens. Mean rate was 2.6% in 2003.

Presentation Notes: A pooled estimate showed that 77% of women with LSIL are positive for high-risk HPV, Prevalence of CIN2/3 among women with LSIL ranges from 12% to 16%. If associated with negative HPV results, probably represents poor sampling (ATLS found association between LSIL with negative HPV and larger os.)

Presentation Notes: Relatively uncommon cytology abnormality, with a mean rate of 0.7% in 2003. Rate of HSIL varies with age, 0.6% in women 20-29 years old, 0.2% in women 40-49 years old

Presentation Notes: Prevalence of CIN 2/3, 53% to 66% in women evaluated with colposcopy/biopsy, 84% to 97% in women evaluated using a loop excision, Approximately 2% of women with HSIL have invasive cancer, More often associated with persistent infection and progression than LSIL, Detecting HSIL has emerged as the central purpose of screening

Presentation Notes: Atypical glandular cells (AGC) is a relatively uncommon cytology abnormality, with a mean rate of 0.7% in 2003. AGC is more common in women 40 yrs and older, Recent series have reported that 3-17% have invasive cancer - including adenocarcinomas of the cervix, endometrium, ovary, and fallopian tube

Presentation Notes: In the clinical setting, HPV testing is performed to identify high risk types only. There are no clinical applications for low-risk HPV testing. DNA testing has a number of well-established clinical uses, including: As an adjunct to cytology (either liquid-based or conventional) for screening women age 30 and older, Management of women with ASC-US cervical cytology results

Presentation Notes: DNA testing has a number of well-established clinical uses, that also includes: Post-colposcopy follow-up of women with abnormal cytology results, Post-treatment follow-up of women who have been treated for CIN 2, CIN 3 [Note: this applies to follow up after any treatment and should not be conducted until 6 months after the treatment], To triage menopausal women with LSIL

Presentation Notes: ASCCP has published interim guidelines for the use of HPV DNA testing as an adjunct to cytology for primary screening of women age 30 and older. This slide shows the recommended management based on HPV result and cytology.

Presentation Notes: One clinical scenario that has received a great deal of attention is the situation in which the HPV DNA positive, but the cytology is negative. The Interim Guidance recommends that women who are HPV DNA positive but with negative cytology should have repeat Pap and HPV testing in 12 months. This slide indicates recommended management of the results obtained 12 months after the initial testing. If repeat HPV testing is still positive for high-risk HPV DNA at the 12 month follow-up and the Pap is negative, both should be repeated in 6 to 12 months; if HPV is still positive, colposcopy is recommended, even if the Pap remains negative. If repeat HPV testing is still positive for high-risk HPV DNA at the 12 month follow-up and the Pap shows LSIL or greater, the woman should undergo colposcopy. If the repeat HPV test is negative and the cytology shows ASC-US, repeat cytology in 3 years and HPV in 12 months is recommended. If the repeat HPV test is negative and the cervical cytology is normal, the woman has a very low risk of having significant cervical disease and can safely wait to be rescreened in 3 years (the majority of women with initially positive HPV results fall in this category). 

Presentation Notes: ASCCP recommends 3 options for initial management of ASC-US in pre-menopausal women: HPV DNA testing, Repeat cytology at 6 and 12 months, Colposcopy, If liquid-based cytology or co-collection is used, HPV DNA testing is the preferred option.

Presentation Notes: ASCCP recommends the following for follow-up management of ASC-US: If HPV reflex testing was used initially: If HPV testing is negative, repeat Pap 12 months, If HPV testing is positive, perform colposcopy

Presentation Notes: ASCCP recommends the following for follow-up management of ASC-US: If repeat cytology was used: If Pap at 6 and 12 months are both negative, patient should undergo routine screening, If Pap at 6 or 12 months is = ASC, perform colposcopy

Presentation Notes: ASCCP recommends the following for post-colposcopy management of ASC-US: If no CIN is identified at the time of colposcopy, management options are: HPV DNA testing at 12 months (it is recommended that HPV DNA testing not be performed at intervals less than 12 months) or, Repeat cytological testing at 6 and 12 months, If CIN is identified, manage per ASCCP guidelines, These recommendations represent no major changes from ASCCP 2001 Guidelines

Presentation Notes: This slides illustrates the risk of CIN 2 or greater based on colposcopy findings.

Presentation Notes: ASCCP recommends colposcopy for all women with ASC-H, based on the fact that a number of studies have reported high rates of CIN 2,3 in these women.

Presentation Notes: LSIL includes specimens previously classified as having mild dysplasia, CIN 1, and HPV change. ASCCP recommends colposcopy for all women with LSIL. This slide shows recommended management based on colposcopy results.

Presentation Notes: The ASCUS LSIL Triage Study (ATLS) showed that women with LSIL and women with ASC-US with high-risk HPV have an identical risk of high-grade neoplasia. For this reason, ASCCP management guidelines for the two conditions are similar, except in special circumstances.

Presentation Notes: This slide compares the 2001 ASCCP guidelines for management of LSIL in postmenopausal women with the new guidelines.

Presentation Notes: This slide compares the 2001 ASCCP guidelines for management of LSIL in pregnant women with the new guidelines.

Presentation Notes: Continuation of new ASCCP guidelines for management of LSIL in pregnant women.

Presentation Notes: This slide shows the ASCCP recommendations for initial management of atypical glandular cells (AGC): Colposcopy with endocervical sampling for all for women, Women = 35 should have endometrial sampling in addition to colposcopy and endocervical sampling, Endometrial sampling is also recommended for women of any age with abnormal bleeding suggestive of a risk for neoplastic endometrial lesions

Presentation Notes: This slide shows the ASCCP recommendations for post-colposcopy evaluation and follow-up of “Atypical Glandular Cells (AGC) Favor Neoplasia or AIS”:

Presentation Notes: This slide shows the ASCCP recommendations for post-colposcopy evaluation and follow-up of “Atypical Endocervical, Endometrial, or Glandular Cells (NOS)”: If biopsies and endocervical sample are negative for neoplasia: If HPV status is unknown: repeat Pap Q6 months x 4, refer to colposcopy for ? ASC

Presentation Notes: This slide shows the ASCCP recommendations for post-colposcopy evaluation and follow-up of “Atypical Endocervical, Endometrial, or Glandular Cells (NOS)”: If biopsies and endocervical sample are negative for neoplasia: If HPV status is known: HPV negative: repeat pap and HPV in 12 months, HPV positive: repeat pap and HPV in 6 months, Refer to colposcopy if HPV+ or cytology ASC-US or greater

Presentation Notes: This slide summarizes the significant differences between the 2001 and new ASCCP guidelines for management of AGC. Note that hysterectomy is preferred in women who have completed childbearing if AIS is identified on excisional procedure

Presentation Notes: This slide shows the ASCCP recommendations for management of High-grade Squamous Intraepithelial Lesion (HSIL). The two recommended management options for women w/ HSIL are: Colposcopic examination with endocervical assessment, OR, Immediate loop electrosurgical excision,

Presentation Notes: If colposcopic examination with endocervical assessment is selected: If colposcopy satisfactory: If biopsy shows CIN 2-3: Excision OR, Ablation,

Presentation Notes: If colposcopic examination with endocervical assessment is selected: If colposcopy satisfactory: If biopsy does not show CIN 2,3 three treatment options are acceptable: Excisional procedure OR, Review of all findings with management based on revised findings OR, Observation with Pap and colposcopy every 6 months for one year, Excisional procedure recommended if HSIL persists,

Presentation Notes: If colposcopy unsatisfactory: excisional procedure

Presentation Notes: This slides lists the ASCCP guidelines for the management of CIN 1. Note that routine use of excisional procedures for CIN 1 is unacceptable,

Presentation Notes: This slides lists the ASCCP guidelines changes for the management of CIN 2,3. Note these minor changes from ASCCP 2001 Guidelines: Cytology follow-up post treatment every 6 months instead of every 4-6 months, Return to routine screening after two negative pap tests instead of 3, Follow-up preferred for CIN 2 in adolescents

Presentation Notes: Currently neither the CDC, USPSTF, ACS, nor the Infectious Disease Society of America (ISDA) recommend routine anal cytology screening, National Guidelines Clearinghouse has no guidelines for anal cytology screening, However New York State Department of Health now recommends anal cytology for HIV-infected individuals who: 1) are MSM, 2) have had genital warts or 3) have had CIN

Presentation Notes: Condom use does not completely prevent transmission of HPV, because the virus is spread via skin contact, not body fluids, but it appears to decrease the efficiency of transmission, as shown in this slide. In addition, condom use has been shown to be associated with higher rates of CIN regression and clearance of HPV infection in women, as well as regression of HPV-associated penile lesions in men. [Hogewoning 2003; Bleeker 2003], This figure shows the rate of HPV infection by frequency of condom use by partner.

Presentation Notes: Merck quadrivalent vaccine for HPV 6, 11, 16, 18 was approved by the FDA in June of 2006. Soon after its approval the Advisory Committee on Immunization Practices (ACIP), which is a CDC advisory committee, released recommendations for vaccination using the HPV vaccine, In November of 2006 the HPV quadrivalent vaccine was included in the Vaccines for Children’s Program, a federally funded vaccine program which provides vaccines for free to both children and adolescents through age 18 who are un-or-under insured. GlaxoSmithKline has filed with FDA for approval for use in the United States of a bivalent HPV 16 and 18 vaccine. The bivalent vaccine is already approved in Australia for clinical use and is expected to be approved in the United States sometimes by the end of 2007 or early 2008.

Presentation Notes: This slide compares the phase III studies evaluating the quadrivalent and the bivalent vaccines. The age of women enrolled in the Phase III studies were very similar, 16-24 for the quadrivalent versus 15-25 years for the bivalent. Both vaccines require three doses: quadrivalent at 0, 2, and 6 mo; bivalent at 0, 1, and 6 mo. The number of patients enrolled in the studies is significant in both sets of Phase III studies. It should be noted that they are separate Phase III studies for the quadrivalent where there is one for the bivalent. Both are double-blinded, placebo-control trials. The number of life time partners is 4 or fewer in the quadrivalent versus 6 or fewer in the bivalent. Mean follow-up was 30 months with the quadrivalent versus 14 months for the bivalent.

Presentation Notes: Very few adverse experiences were seen in recipients of the quadrivalent vaccine. These included injection site pain, swelling, erythema, and pruritus. However, 94% of the vaccine recipients considered these reactions at the site of injection to be mild to moderate and only 1 in a 1,000 subjects discontinued the study. Therefore, there is widespread acceptance at this point of the safety of these vaccines and most experts believe that the HPV vaccines are going to prove to be quite safe.

Presentation Notes: The vaccine is most effective when administered before onset of sexual activity (see FUTURE I efficacy rates for naïve women vs. general population, for example). When we consider what age should be targeted for vaccination we need to remember that over 80% of sexually active adolescents become exposed to HPV within 3 years of sexual activity. [Winer 2005], For this reason, experts believe it would be best to administer the HPV vaccine prior to sexual activity.

Presentation Notes: There has been considerable discussion about whether HPV testing should be conducted prior to vaccination. Almost no women would have been exposed to all four vaccine types present the quadrivalent vaccine. Therefore, it does not make sense to pretest women prior to vaccination. In addition, many women have been exposed to HPV but have spontaneously cleard the HPV and therefore will no longer be HPV DNA positive but would have been previously exposed to HPV. In the vaccine trials these women were excluded through the use of serological assays, but these serological assays one are not widely available and are not well standardized. There also is considerable data indicating that serological testing is relatively insensitive indicator of previous exposure. In some studies half of women which are documented to be exposed to HPV 16 have not become serologically positive on follow-up. For these reasons, most experts consider pre-vaccination screening is be a waste of money and an unnecessary barrier to vaccination.

Presentation Notes: Vaccine efficacy has not yet been proven in males. Trials are underway evaluating both the bivalent and the quadrivalent vaccines, but results are not expected until 2008. Also, HPV vaccine is different than vaccines such as rubella and chicken pox with respect to herd immunity. With common childhood contagious diseases it is important to vaccinate males in order to obtain herd immunity. However, because HPV is transmitted sexually, herd immunity is not going to become an important factor until very high coverage rates are obtained in the population. High coverage rates are necessary because otherwise the high transmitter population will not be reached. High transmitters are individuals who have numerous sexual contacts; they appear to be responsible for a significant amount of the transmission of sexually transmitted disease. Because of these considerations, there are currently no recommendations for male vaccination in the United States.

Presentation Notes: There are several reasons why cervical cancer screening should continue after vaccination: Because there is no national registry, providers will not know whether or not an individual has been vaccinated. Recall tends to be poor about specific vaccinations—It is unlikely that many 20 and 30 year olds will remember whether or not they were vaccinated for HPV when they were 11 or 12 years old. If vaccinated after onset of sexual activity, an individual could have been exposed to HPV before vaccination. Individuals can become infected with HPV types for which the vaccine is not protective.

Presentation Notes: The private sector list price for the vaccine is about $120 per dose; $360 for full series. This does not include cost of vaccine administration. The federal Vaccines for Children (VFC) program provides free vaccines to children and adolescents less than 19 years old who are uninsured, eligible for Medicaid, American Indian, or Alaska native. The Immunization Grant Program (Section 317) is a federal program that awards grants to public health agencies to aid with vaccine costs for children who do not qualify for VFC. Some state health departments provide free or low cost vaccines to individuals without health insurance coverage for vaccines. Some private insurance companies may not cover vaccine and administration costs; large group insurance companies usually cover the cost of recommended vaccines and their administration.

Presentation Notes: ACOG, USPSTF, and ACS all recommend that Pap testing be initiated: 3 years after vaginal intercourse, By 21 years of age

Presentation Notes: Because of the high rate of HPV in adolescents with atypical Pap test results, use of HPV for triage is of dubious benefit in this population. Based on the Atypical Squamous Cells of Undetermined Significance/Low-Grade Squamous Intraepithelial Lesion Triage Study (ALTS), 71% of women age 18-22 would be referred for colposcopy if reflex HPV testing were used for triage of ASC-US in this group. If cytology only were used for triage, 66% would be referred. In addition, 2006 Consensus Guidelines recommend 1 year follow-up for adolescents (20 and under) with ASC-US regardless of the HPV status.

Presentation Notes: Adolescents should not be screened unless they have been sexually active for 3 years, Rates of ASC-US are quite high in adolescents due to high prevalence of HPV, Cervical cancer is extremely rare in adolescents in the U.S. 

Presentation Notes: Over the course of 36 months, LSIL lesions will regress in the majority of adolescents and young women.

Presentation Notes: This slide reviews the ASCCP recommendations for the management of ASC-US or LSIL in adolescents. Note that all should have repeat cytology in 12 months regardless of HPV status.

Presentation Notes: This slide reviews the ACOG recommendations for the management of ASC-US and LSIL in adolescents. Unlike the ASCCP recommendations, ACOG guidelines differ for ASC-US and LSIL

Presentation Notes: This slide shows the ASCCP recommendations for the management of high-grade squamous intraepithelial lesion (HSIL) in adolescents. All adolescents with HSIL should undergo colposcopy. If endocervical curettage is positive or if colposcopy is unsatisfactory, an excisional procedure is recommended.

Presentation Notes: If biopsy shows CIN 2 or less: The preferred management option is follow-up with Pap and colposcopy every 6 months (If HSIL or CIN 2 persists at 24 month, excisional procedure is recommended). An acceptable option is treatment with excision or ablation

Presentation Notes: If endocervical curettage is positive or if colposcopy is unsatisfactory, an excisional procedure is recommended. If biopsy shows CIN 3, there are two recommended options: Excision OR, Ablation

Presentation Notes: This slide reviews the ASCCP recommendations for the management of CIN 1 in adolescents. Note that the recommendations are identical to those for the management of ASC-US and LSIL in adolescents.

Presentation Notes: Women age 30 or older who test positive for HPV but have a negative Pap test need to be reminded that: Diligent follow-up is important, They need to return in 12 months for a Pap and HPV Test, If HPV is still present at follow-up, colposcopy will be recommended even if the Pap is still negative

Presentation Notes: Women who test positive for HPV need to be reminded that: Most women will have HPV at some point, There is no way of knowing how long HPV has been present, Having HPV is not a sign of infidelity

Presentation Notes: Women who test positive for HPV also need to be reminded that: Most women who have HPV do not develop abnormal cells of cancer, Women who have HPV in their cells a long time are at greater risk for developing abnormal cells or cancer

Presentation Notes: Women need additional information about HPV and cervical cancer. This slide shows five HPV Educational Messages.

Presentation Notes: Many women with an initial screening high-risk HPV will not have pre-cancer on further evaluation or be diagnosed with cancer. However, as many as 25% to 40% of women with persistent high-risk HPV develop cytological abnormalities when evaluated 1 to 3 years after HPV detection. Since 30% of cervical cancers are associated with viral types that are not covered by the vaccine, women will continue to need cervical cancer screening even if vaccinated.

Presentation Notes:

Presentation Notes:

Presentation Notes: HPV has been associated with a number of human cancers. The virus is causative in cervical and anal cancer and a co-factor in other cancers.

Presentation Notes: HPV also is causative for external genital warts. In this presentation, we’ll focus on screening and prevention of cervical cancer and management of external genital warts, but will also provide an overview of the screening and prevention of anal cancer.

Presentation Notes: Virtually all cervical cancers are associated with persistent infection with high-risk HPV types. Data from a variety of studies (including case-control, prospective cohort series, and case series) have confirmed that certain HPV types are carcinogenic for the cervix: 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, others are probably carcinogenic, including: 26,53 66 68,73 82.

Presentation Notes: In the US in 2007, estimated to be about 11,150 cases of cervical cancer and 3,670 deaths [ACS 2007], Worldwide: 288,000 deaths per year from cervical cancer [IARC 2005], 80% of deaths occur in developing countries [IARC 2005], Cervical cancer screening is estimated to cost $3.4 billion annually. [Insinga 2004.]

Presentation Notes: The strength of the evidence for carcinogenicity or a causal role in cancer varies by site and HPV type. HPV 16 and 18—evidence of causal role in cancer of vagina, vulva, penis, anus, HPV 16—evidence of carcinogenicity in oral cavity, oropharynx, periungual skin

Presentation Notes: HPV 18—some evidence of carcinogenicity in oral cavity, HPV 6, 11, 16, and 18—limited evidence for carcinogenicity in laryngx

Presentation Notes: This slide shows the cancers associated with HPV infection, the number of cases of each, and the proportion of cases attributable to HPV. Approximately 11,150 women are diagnosed with cervical cancer each year in the United States--100% of these are believed to be attributable to HPV, meaning essentially that all cervical cancers are associated with infection with high-risk HPV. Overall in the United States each year approximately 24,479 cancers are directly attributable to high-risk types of HPV.

Presentation Notes: This slide shows the percentage of Pap tests showing ASC-US, LSIL or HSIL that are associated with HPV 16. Approximately 400,000 women have an ASC-US Pap annually associated with HPV 16. LSIL is less common than is ASC-US, but HPV infections are much more common in LSIL than ASC-US Paps—295,000 women each year are diagnosed in the United States with an HPV 16 associated LSIL Pap. About 182,100 HSIL are associated with HPV 16 annually. Combined, almost 900,000 women have an HPV 16 associated abnormal Pap smear each year in the United States. This is a huge burden of disease attributable to HPV 16.

Presentation Notes: Approximately 6.2 million new HPV infections occur in the U.S. each year. [Weinstock 2004], At any given time, about 26.8% of women 14-59 years old have HPV. [Dunne JAMA 2007 NHANES data], The lifetime risk of HPV infection is about 75% for sexually active individuals. [Koutsky 1997]

Presentation Notes: HPV prevalence varies by age, and is highest for young women, decreasing in the middle age groups. This graph shows the age-specific prevalence of the high-risk HPV types. Note that the prevalence by type varies somewhat by region, for reasons that are not yet known. This figure shows data from Portland and Guanacaste.

Presentation Notes: In a study of 603 female college students conducted by Winer and colleagues (mean follow up: 41 months). At entry into the study 19.7% of the college-aged women were already HPV DNA positive and over the first two years of follow-up 39% of the women who were initially HPV DNA negative became HPV DNA positive. High-risk types of HPV such as HPV 16 and 18 were the types most commonly identified in these young college-aged women.

Presentation Notes: In a study of 603 female college students conducted by Winer and colleagues (mean follow up: 41 months). High-risk types of HPV were the types most commonly identified in these young college-aged women. Note the prevalence of infection for the types present in the HPV vaccine: Type 6: 9.9%, Type 11: 0.9%, Type 6/11: 2.1% [could not be individually tested for HPV types 6 and 11], Type 16: 10.3%, Type 18: 5.6%

Presentation Notes: In a literature review by Dunne and colleagues, 40 published studies on HPV prevalence in men were reviewed: Of these, 27 evaluated multiple specimens or sites, 10 evaluated a single site or specimen, and 3 evaluated risk factors or optimal anatomic sites/specimens for HPV detection, In the group of studies that evaluated multiple sites or specimens, the prevalence of HPV in men varied from 1.3% to 72.9%. Studies with immunocompromised persons were not included in this analysis.

Presentation Notes: In a literature review by Dunne and colleagues, 40 published studies on HPV prevalence in men were reviewed: Of these, 27 evaluated multiple specimens or sites, 10 evaluated a single site or specimen, and 3 evaluated risk factors or optimal anatomic sites/specimens for HPV detection, In the group of studies that evaluated multiple sites or specimens, the prevalence of HPV in men varied from 1.3% to 72.9%. Studies with immunocompromised persons were not included in this analysis.

Presentation Notes: Several studies have evaluated the frequency of HPV infection among adolescents. This study included 60 girls 14-17 years old who lived in Indianapolis, Indiana. The girls had pelvic exams, interviews, and cervical samples tested for HPV at 3 monthly intervals for 2 years. In addition, the girls kept a detailed sexually diary and self-collected a vaginal swab for HPV DNA testing on a weekly basis for up to 15 weeks. Researchers found that 80% of participants had high-risk HPV at some point. The only 3 who tested negative for all specimens denied any sexual exposure.

Presentation Notes: Study by Ho and colleagues, 1998. 608 college students (mean age 20 years) recruited in New Brunswick, NJ. At enrollment 26% had high-risk HPV identified. Women were followed every 6 months for 36 months or more. At each visit, women completed questionnaire on lifestyle and had cervicovaginal lavage. At baseline and then annually, the women had a pelvic exam with Pap smear. The cumulative 36-month incidence of high-risk HPV in women negative at baseline was 43%. By 12 months after infection, 70% had cleared their infection, By 24 months, just 9% still infected. Over 90% had cleared their infection.

Presentation Notes: Sexual intercourse is the primary route of HPV transmission. HPV is transmitted via direct genital contact (rather than via body fluids, like most STIs). [CDC. HPV Information for Clinicians], Receptive anal intercourse is strongly associated with HPV infection. [Burchell 2006], Genital contact in the absence of intercourse is a plausible means for HPV transmission, but the risk associated with this contact is much lower than that for intercourse. [Burchell 2006; CDC HPV Information for Clinicians], The virus also can be transmitted via oral-genital contact. Transmission is not thought to occur via inanimate objects, such as clothes. [CDC HPV Information for Clinicians]

Presentation Notes: Progression to precancer occurs when infection with HPV high risk types persists over time. Only small minority of women with HPV detectable by DNA assays have microscopic cervical abnormalities; however, at follow up 1 to 3 years later, 25% to 40% will have cervical abnormalities. [Moscicki 2006] These data point to the importance of persistence of HPV infection. In most cases, HPV infection—with low or high-risk types—is cleared by the body. Studies have shown that viral clearance is not often followed by subsequent infection with the same genotype. [Moscicki 2006] Less than half of women who develop HPV infection will have persistence of the same HPV type 12 months later. [Trottier 2006], Persistent infection is defined as detection of the same HPV genotype 2 or more times within a given interval of time; however, the duration of time defining persistence is not yet agreed upon. [Moscicki 2006], The HPV type affects both the likelihood of persistence and the risk of progression to precancer. HPV type 16 persists longer than other types and also is especially carcinogenic, with a risk of CIN-3 of 40% at 5 years. [Moscicki 2006], There are currently no data on the natural history of HPV infection in men. [CDC HPV Information for Clinicians]

Presentation Notes: HPV-related cancers tend to occur at transformation zones, Transformation zones are areas at which one type of epithelium contacts and gradually replaces another through the process of metaplasia. Transformation zones are located in the cervix, anus, and tonsils.

Presentation Notes: This illustration shows the transformation zone in the cervix—the site where between the squamous cells of the exocervix and the columnar cells of the endocervix.

Presentation Notes: In almost all studies of HPV infection, the most consistent predictors of infections are measures of sexual activity, In the Ho study of college women, the strongest risk factor for incident infection was having a main regular sexual partner who had 6 or more lifetime partners (adjusted relative risk 10.1). Specific risk factors for HPV infection include [Ley 1991]: Multiple partners, Younger age at sexual debut, Lack of condom use, Because the virus is transmitted via skin to skin contact, condoms don’t completely prevent infection. However, a 2006 study found that consistent condom use by their partners reduced the risk of HPV infection in female university students (adjusted hazard ratio = 0.3). [Winer 2006]

Presentation Notes: Epidemiologists have not yet clearly defined which risk factors are associated with increased viral persistence and which are associated with an increased risk of neoplastic progression. There appears to be overlap but the two processes are not identical. HPV type (e.g. type 16) and increasing age have clearly been identified as co-factors in neoplastic progression and in progression. Smoking is clearly associated with neoplastic progression, but its effects on persistence of infection are less clear. Recent studies have suggested that condom use reduces the risk of high-grade cervical lesions and increases HPV clearance. [Hogewoning 2003], Women with HIV have prolonged HPV persistence, even if their CD4 counts are normal. [Moscicki 2004], Some studies have suggested that OC use and the presence of other STIs may act as cofactors in neoplastic progression and/or persistence of HPV infection. However, there is insufficient evidence to recommend that women with high-risk HPV infection should discontinue OC use.

Presentation Notes: More than 120 types of HPV have been identified. [De Villiers 2004; zur Hausen 2000], About 40 types can infect the genital tract. [Munoz 2006], Approximately 13 to 19 are considered high-risk types, meaning that persistent infection with these types is associated with an increased risk of cervical, anogenital, and other cancers (number considered high risk has varied in different studies). [De Villiers 2004; zur Hausen 2000; Munoz 2003], The most important high-risk types are 16 and 18. Type 16 alone causes half of all cases of cervical cancer. Type 18 causes another 20% of all cases. [Munoz 2003], In fact, persistent infection with high-risk HPV is responsible for 99.7% of cervical cancers. [Walboomers 1999], Low-risk HPV types, the most important of which are 6 and 11, are associated with external genital warts, or condylomata acuminata, and with low-grade cervical lesions. [Soper 2006]

Presentation Notes: This slide shows the relative frequency of detection of HPV types for specimens associated with cervical cancer. Notice that many of the lesions are associated with DNA from type 16 or 18 worldwide.

Presentation Notes: Persistent infection with high-risk types of HPV is necessary for the progression of high grade lesions to invasive cancer. [Trottier 2006]

Presentation Notes: Average episodes last 4-20 months [Trottier 2006], Most infections are cleared by the immune system. Only a small proportion of women with a particular HPV type test positive for the same type in subsequent testing [Trottier 2006], Most studies show that <50% of women are infected with the same HPV type 12 months later [Trottier 2006], Persistence of infection with HPV leads to abnormal clonal progression in the cervical epithelium and eventually may lead to invasive cervical carcinoma. [Moscicki 2006], Believed that carcinoma develops from infections that persist with continued viral replication within the squamous epithelium. [Trottier 2006], HPV type 16 infection tends to persist longer than infection with other HPV types. [Trottier 2006]

Presentation Notes: The risk of progression to invasive cervical cancer varies based on the degree of dysplasia, as measured by the cervical intraepithelial neoplasia (CIN) stage. CIN 1 = mild dysplasia, CIN 2 = moderate dysplasia, and CIN 3 = severe dysplasia, or carcinoma in situ. [ASCCP Web site-spectrum of disease 2006], Note that 60% of CIN 1 lesions will regress, compared with only 33% of CIN 3 lesions.

Presentation Notes: Figure Notes: Etiologic model of human papillomavirus (HPV) infection as a necessary cause of cervical cancer incorporating the role of host, reproductive, lifestyle, and viral co-factors. Abbreviations: CIN: cervical intraepithelial neoplasia (a histological classification); LSIL: low-grade squamous intraepithelial lesions; HSIL: high-grade squamous intraepithelial lesions (the SIL classification is the cytological analogue of the CIN scheme); HLA: human leukocyte antigen. Source: Franco and Harper, 2005, with permission. It is generally now accepted that infection with HPV is a necessary, but not sufficient, cause of virtually all cases of cervical cancer worldwide. [Trottier 2006], This model shows how cofactors are involved in the development of cervical cancer. Note that transmission of HPV occurs through skin-to-skin anogenital contact; intercourse is not necessary for infection. 20% of women who have never had vaginal intercourse test positive for HPV DNA. [Ley 1991]

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Presentation Notes: 90% caused by HPV types 6 and 11, Affects 1% of sexually active women age 18 to 45 in United States, CDC estimates 500,000 to 1 million cases annually, 240,000 initial office visits per year, 1% of sexually active US women age 18 to 45 affected, 1/3 of all STI dollars spent annually, Cost $167 million annually

Presentation Notes: Approximately 1% of sexually active individuals in the US have clinically evident external genital warts (EGW) or condyloma acuminata. EGW are associated with HPV low-risk types, 90% associated with types 6 and 11, Natural history of EGW: Lesions can resolve untreated (about 20%), remain unchanged, or increase in size or number. Women with EGW should receive cervical cancer screening according to published guidelines.

Presentation Notes: This slide shows the relative frequency of detection of HPV types for specimens associated with EGW lesions. Notice that the majority of lesions are associated with DNA from type 6 or 11.

Presentation Notes: EGW can be diagnosed by visual appearance. Application of vinegar or acetic acid is not recommended. If necessary, diagnosis can be confirmed by biopsy. HPV tests are not indicated. (Picture is of extensive EGW in the perianal area).

Presentation Notes: Primary goal of treatment of EGW is removal for cosmetic reasons, Exact impact of treatment on reducing infectivity is unknown, In most patients, treatment is successful at removing lesions, Recurrences are common, Patient and provider-applied treatments are available

Presentation Notes: Two treatment modalities are available for EGW: Provider delivered: Trichloroacetic acid/bichloroacetic acid [TCA/BCA], Cryotherapy (liquid nitrogen and other methods), Excision, laser ablation, or electrosurgery, Patient applied, Imiquimod (Aldara) 5% Cream—works by modulating the immune system, Podophyllotoxin (Condylox) 0.5% gel

Presentation Notes: General principles: No single treatment is ideal for all patients, Treatment choice is based on size, number, and location of lesions, Small isolated lesions will often respond to clinician applied therapy such as TCA, Large lesions or multiple site involvement, may be more amenable to other therapy options, Clinicians should use the least invasive and least costly approach, Patient preference is important in choosing therapy

Presentation Notes: The PPFA created a treatment algorithm for the most cost-effective means for treating EGW based on information gathered from retrospective chart review. Chart were reviewed from 5 Planned Parenthood clinic sites (Houston, Chicago, New York, Western Washington, and Minnesota). One hundred charts from each site with EGW diagnosis and documentation of wart clearance were evaluated for treatment modalities and time to clearance. Financial evaluations were conducted at each clinic to determine payor mix and reimbursement levels for each payor category.

Presentation Notes: Talking points: Key finding: 47% of clinic resources were spent on the 26% of patients who required 4 or more clinic visits before clearance of EGW

Presentation Notes: This slides shows the Planned Parenthood Federation of America (PPFA) treatment algorithm for EGW. Note that ablative therapy, such as lasers, could be considered if lesions persist despite treatment.

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Presentation Notes: • It’s important to be aware of the goal of any screening program. The goal of cervical cancer screening is to identify and treat high-grade cervical cancer precursors, thus reducing a woman’s risk of developing invasive cervical cancer. In addition, it is important to minimize costs and unnecessary and potentially hazardous evaluations and treatment, Positive HPV testing or cytology showing CIN 1 identify many women who will never be at risk for cervical cancer. In contrast, cytology showing CIN 2 or greater reflects a high-grade cancer precursor and will identify women who need treatment or extremely careful follow-up.

Presentation Notes: The current approach to cervical cancer prevention: •Screen using cervical cytology in women of all ages according to published guidelines (cytology with or without HPV DNA testing), •Evaluate women with positive screening results using colposcopy and cervical biopsy, Treat women with biopsy-confirmed high-grade cervical cancer precursors, • [Speaker: Complete management and HPV DNA testing are covered in subsequent modules.]

Presentation Notes: Both conventional Papanicolaou tests and liquid-based cytology are acceptable screening methods, Recent well-controlled clinical trials have found little difference in performance of the two methods for identifying high-grade disease, Liquid-based cytology is preferred by most laboratories, and it facilitates "reflex" HPV as well as gonorrhea/chlamydia testing

Presentation Notes: Conventional and liquid-based Pap tests perform similarly for detecting high-grade disease. In the Cape Town study listed here, sensitivity was slightly higher for the conventional Pap test than the liquid-based Pap test.

Presentation Notes: HPV infections are very common in young women and frequently result in abnormal Pap results, The evaluation of minor cytological abnormalities in young women is expensive, causes considerable anxiety, and can result in unnecessary treatments, HPV prevalence and cervical cancer incidence are a function of a woman’s age: there is a high prevalence of HPV infection in younger women, which drops considerably as women age. However, as the prevalence of HPV declines, the incidence of CIN 3 and cancer increases. Based on these two opposing forces, the ideal age to start screening with combined HPV testing and cytology is in the early 30s.

Presentation Notes: These data are from the SEER Cancer Statistics Review 1975-2003, for all races. Note the increase in incidence of cervical cancer with age among adolescents and young women.

Presentation Notes: Within the United States, expert committees from American Cancer Society (ACS), American College of Obstetricians and Gynecologists (ACOG), and United States Preventive Services Task Force (USPSTF) recommend starting cervical cancer screening 3 years after initiation of sexual intercourse or no later than 21 years old.

Presentation Notes: ACOG: No age to stop screening specified, Notes that older women with a lifetime of screening are at low risk, ACS: Can stop cervical cancer screening if 70 or older and have 3 documented, consecutive normal Pap tests within preceding 10 years (not if history of DES exposure, cervical cancer, or immunosuppression), If HPV positive, continue screening, USPSTF: Notes that risk of cancer and yield of screening decline in middle age, Recommends against routine screening in women over age 65, if adequate recent screening and not otherwise at high risk

Presentation Notes: ACS: Annual screening with conventional Pap test, Every 2 years for screening with liquid-based test, At age 30 if a woman has had 3 normal consecutive Pap tests, can change to every 2 to 3 years (but not if she has history of DES exposure or immunosuppression)

Presentation Notes: ACOG: Annually if <30 years old, At age 30 if 3 normal consecutive Pap tests, change to every 2 to 3 years (but not if she has history of DES exposure or immunosuppression), For women age 30 or older, either Pap or Pap plus HPV can be used for screening, At age 30 if HPV and Pap are both negative, change to no more frequently than every 3 years, USPSTF : Cervical cancer screening interval: at least every 3 years. The guidelines note that there is no direct evidence to support the clinical utility of more frequent screening.

Presentation Notes: Women who have had a hysterectomy are one-tenth as likely to have an abnormal Pap than women with an intact cervix. High-grade neoplasia is uncommon in women who have had a hysterectomy (about 0.18 per 1000). [Pearce 1996], ACS, ACOG, and USPSTF all recommend against routine screening of women who have had a hysterectomy for benign disease.

Presentation Notes: The Bethesda system was developed in 1991 to standardize the reporting the results of cervical cytology. It was updated in 2001. Two types of epithelial cell abnormalities are designated in the Bethesda system: squamous cell and glandular cell abnormalities. Note that LSIL incorporates: Mild dysplasia, Cervical intraepithelial neoplasm (CIN) 1, HSIL incorporates: Moderate and severe dysplasia, Carcinoma in situ, CIN 2, CIN 3

Presentation Notes: This is the Bethesda System terminology for glandular cell abnormalities.

Presentation Notes: ASC-US is the most common cytological abnormality in the United States—mean rate 4.7% in 2003. About 2.5 million cases of ASC-US are reported each year. The prevalence of CIN 2/3 among women with ASC-US is 7-12% in the U.S. Almost half of all cases of CIN 2/CIN 3 are diagnosed in women with ASC-US. Women with a cytological result of ASC-US require follow-up.

Presentation Notes: ASC-H is a designation given to specimens that show atypical squamous cells for which high-grade intraepithelial lesions (HSIL) cannot be excluded; specimens given this designation include both HSIL and mimics. It’s an uncommon finding, with a mean rate of just 0.43% in 2003. The risk of CIN 2/3 is higher for ASC-H than ASC-US (40% vs 15%). The prevalence of CIN2/3 among women with ASC-H ranges from 26% to 68%, It is important to consider the equivocal nature of this designation when making decisions about further evaluation. For example, clinicians should examine all of a patient’s pathology reports and colposcopy findings prior to making a recommendation about excision procedures.

Presentation Notes: LSIL is a common cytology abnormality that usually represents self-limited HPV infection, It is found more commonly in liquid-based cytology specimens than in conventional Pap specimens. Mean rate was 2.6% in 2003.

Presentation Notes: A pooled estimate showed that 77% of women with LSIL are positive for high-risk HPV, Prevalence of CIN2/3 among women with LSIL ranges from 12% to 16%. If associated with negative HPV results, probably represents poor sampling (ATLS found association between LSIL with negative HPV and larger os.)

Presentation Notes: Relatively uncommon cytology abnormality, with a mean rate of 0.7% in 2003. Rate of HSIL varies with age, 0.6% in women 20-29 years old, 0.2% in women 40-49 years old

Presentation Notes: Prevalence of CIN 2/3, 53% to 66% in women evaluated with colposcopy/biopsy, 84% to 97% in women evaluated using a loop excision, Approximately 2% of women with HSIL have invasive cancer, More often associated with persistent infection and progression than LSIL, Detecting HSIL has emerged as the central purpose of screening

Presentation Notes: Atypical glandular cells (AGC) is a relatively uncommon cytology abnormality, with a mean rate of 0.7% in 2003. AGC is more common in women 40 yrs and older, Recent series have reported that 3-17% have invasive cancer - including adenocarcinomas of the cervix, endometrium, ovary, and fallopian tube

Presentation Notes: N/A

Presentation Notes: The Hybrid Capture 2 assay uses a pooled mixture of probes to detect 13 of the high risk HPV types (16,18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 and 68). It does not identify the HPV type in an individual clinical sample.

Presentation Notes: Note that some laboratories routinely test for both high- and low-risk types; these facilities should be avoided.

Presentation Notes: In the clinical setting, HPV testing is performed to identify high risk types only. There are no clinical applications for low-risk HPV testing. DNA testing has a number of well-established clinical uses, including: As an adjunct to cytology (either liquid-based or conventional) for screening women age 30 and older, Management of women with ASC-US cervical cytology results

Presentation Notes: DNA testing has a number of well-established clinical uses, that also includes: Post-colposcopy follow-up of women with abnormal cytology results, Post-treatment follow-up of women who have been treated for CIN 2, CIN 3 [Note: this applies to follow up after any treatment and should not be conducted until 6 months after the treatment], To triage menopausal women with LSIL

Presentation Notes: Use of HPV testing for cervical cancer screening has 2 key benefits: Allows for less frequent screening, Rationale: a normal Pap and a negative HPV test give a high assurance that cervical cancer is not present and will not likely occur in the next few years [when both tests are negative, chance of concurrent CIN 2 or greater is 1 in 1,000; chance of developing CIN 2 or greater within 3 years is less than 2 in 1,000], Identifies women who need increased surveillance, Rationale: a positive HPV test and a normal Pap reflects increased risk for either missed disease or for the subsequent development of CIN 2/3 and cancer

Presentation Notes: HPV DNA testing should NOT be used in certain circumstances, including: To triage women with Pap results other than ASC-US (with the exception of postmenopausal women with LSIL), As adjunct to Pap testing in primary screening of women : <30 years old (Triage in women under 30 years old is not recommended because HPV is highly prevalent and the prevalence of cervical cancer is low.), Status-post total hysterectomy for benign disease

Presentation Notes: ASCCP has published interim guidelines for the use of HPV DNA testing as an adjunct to cytology for primary screening of women age 30 and older. This slide shows the recommended management based on HPV result and cytology.

Presentation Notes: One clinical scenario that has received a great deal of attention is the situation in which the HPV DNA positive, but the cytology is negative. The Interim Guidance recommends that women who are HPV DNA positive but with negative cytology should have repeat Pap and HPV testing in 12 months. This slide indicates recommended management of the results obtained 12 months after the initial testing. If repeat HPV testing is still positive for high-risk HPV DNA at the 12 month follow-up and the Pap is negative, both should be repeated in 6 to 12 months; if HPV is still positive, colposcopy is recommended, even if the Pap remains negative. If repeat HPV testing is still positive for high-risk HPV DNA at the 12 month follow-up and the Pap shows LSIL or greater, the woman should undergo colposcopy. If the repeat HPV test is negative and the cytology shows ASC-US, repeat cytology in 3 years and HPV in 12 months is recommended. If the repeat HPV test is negative and the cervical cytology is normal, the woman has a very low risk of having significant cervical disease and can safely wait to be rescreened in 3 years (the majority of women with initially positive HPV results fall in this category).

Presentation Notes: In 2005 the American College of Obstetricians and Gynecologists (ACOG) made the following recommendation regarding using high-risk HPV DNA testing concurrently with cervical cytology. This is a Level A recommendation which is ACOG's highest level of recommendation.

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Presentation Notes: ASCCP recommends 3 options for initial management of ASC-US in pre-menopausal women: HPV DNA testing, Repeat cytology at 6 and 12 months, Colposcopy, If liquid-based cytology or co-collection is used, HPV DNA testing is the preferred option.

Presentation Notes: ASCCP recommends the following for follow-up management of ASC-US: If HPV reflex testing was used initially: If HPV testing is negative, repeat Pap 12 months, If HPV testing is positive, perform colposcopy

Presentation Notes: ASCCP recommends the following for follow-up management of ASC-US: If repeat cytology was used: If Pap at 6 and 12 months are both negative, patient should undergo routine screening, If Pap at 6 or 12 months is = ASC, perform colposcopy

Presentation Notes: ASCCP recommends the following for post-colposcopy management of ASC-US: If no CIN is identified at the time of colposcopy, management options are: HPV DNA testing at 12 months (it is recommended that HPV DNA testing not be performed at intervals less than 12 months) or, Repeat cytological testing at 6 and 12 months, If CIN is identified, manage per ASCCP guidelines, These recommendations represent no major changes from ASCCP 2001 Guidelines

Presentation Notes: This slides illustrates the risk of CIN 2 or greater based on colposcopy findings.

Presentation Notes: This slide compares the 2001 and 2006 ASCCP recommendations for the management of postmenopausal women or immunosuppressed women with ASC-US. The new recommendations suggest that these women are treated in the same manner as women in the general population who have ASC-US.