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2. Cervical Cancer Screening and HPV Vaccination
September 6, 2017
Laura Chambers-Kersh

3. Recall epidemiology of cervical cancer and the role of HPV
Review recommended screening protocols for cervical cancer
Examine efficacy and safety of HPV vaccine
Review vaccination schedule for HPV
Strategize on how best to talk about HPV vaccine

4. How many cases of cervical cancer are there per year in the US?
1000
2000
5000
10,000
13,000

5. True or False
Most young women will clear an HPV infection within 8 to 24 months
The prevalence of cervical HPV infection decreases after the age of 30, but the likelihood of persistent infection increases
among women diagnosed with invasive cervical carcinoma, 70% have never had a Pap smear
cytologic screening for cervical cancer with Pap smears has never been evaluated in a randomized trial

6. Risk Factors oral contraceptive use cigarette smoking HIV
Other immunosuppression
Early onset of intercourse
Multiple partners
Low socioeconomic status
rural
Being non-white

7. When did the US start using the pap smear to screen for cervical cancer?
The United States adopted screening with the Pap test in the 1950s, and by the mid-1980s cervical cancer incidence decreased by 70 percent

8. When to start screening?

9. When to start screening?
Starting at age 21, women should be screened even if they report sexual abstinence.
In the United States, the age-adjusted incidence of cervical cancer in women ages 15 to 19 years is 0.1 per 100,000

10. Of the approximately 30 to 40 HPV genotypes that infect the genital tract mucosa, types 16 and 18 are responsible for about 70 percent of cervical cancer and 50 percent of cervical cancer precursors

11. Screen every three years when < 30
In women <30 the poor specificity and correspondingly poor positive predictive value limit the usefulness of HPV testing as a screening modality

12. How do we screen women >30?
women age ≥30 years and older be screened with either:
Pap test every three years
Co-testing (Pap test and HPV testing) every five years if both initial tests are negative

13. When to stop screening?

14. You can stop screening women at age 65 as long as they meet all of the criteria below except:
No increased risk (ie, history of abnormal screening, current smoker or history of smoking, unknown screening history, previous HPV-related disease, new partners, immunocompromised, in utero diethylstilbestrol exposure).
Adequate prior screening: two negative consecutive co-tests or three negative Pap tests within the past 10 years, with the most recent test within the previous five years
No history of high-grade dysplasia or worse

15. True or False
Pap test abnormalities among previously screened older women have better positive predictive value for significant pathology than in younger women
FALSE!
A study in pre- and postmenopausal women who had Pap tests showing atypical squamous cells (cannot exclude high-grade lesion, ASC-H) found high-grade histology in 22 percent of pre-menopausal women, compared with 6 percent of postmenopausal women

16. Not a lot of good data about when to stop
A 2013 systematic review of 24 studies found no conclusive evidence to support a specific age to stop cervical cancer screening, as none of the reviewed studies looked specifically at this question
A subsequent observational study found that when corrected for the high prevalence of hysterectomy in the United States (1/3 of all women by age 60), the incidence of invasive cervical cancer in older women may be higher than previously thought and may not decline with increasing age

17. What about older women who have never been screened?
Some experts suggest screening with either Pap test every two to three years or co-testing every five years
The US Preventive Services Task Force (USPSTF) suggests that screening be continued until age 70 or 75

18. Older women who have never been screened have the highest incidence of and mortality from cervical cancer and benefit the most from screening

19. TRUE OR FALSE
Total hysterectomy (with cervix removed) and no history of cervical cancer or CIN can stop screening
Women with a subtotal hysterectomy can stop screening
Women who have had a hysterectomy for CIN2 or 3 should have screening for 10 years after the surgery
Smokers should continue to have screening after age 65
Recipients of the HPV vaccine can stop screening after 3 normal pap smears

20. Frequency of Testing
How confident are you that you can do this every 3-5 years?
a population-based study of over 300,000 women aged 30 and older found that women who had negative co-testing had a 0.16 percent cumulative incidence of CIN 3 or worse at five years

21. Primary HPV Testing

22. Screening Rates in the US
In a survey of screening in the United States in 2010, what percent of women aged 21 to 65 years with a cervix reported having had a Papanicolaou (Pap) test within the preceding three years ?
95%
87%
62%
53%

29. HPV VACCINE

30. 90% of anogenital warts are caused by which HPV types?
6 and 11
16 and 18
31 and 45
31, 33, and 52

31. 90% of cervical cancers are caused by the following HPV types?
16 and 18
31, 33, 45, 52, and 58
A and B
None of the above

32. Vaccines Gardisil Gardisil-9 Cervarix 6, 11, 16, 18
6, 11, 16, 18, 31, 33, 45, 52, 58
Cervarix
16, 18

33. At what age should you start vaccinating
9-10
11-12
13-14
15 and older

34. TRUE OR FALSE
None of the available HPV vaccines treat or accelerate the clearance of preexisting vaccine-type HPV infections or related disease
A history of an abnormal Papanicolaou test, genital warts, or HPV infection is a contraindication to HPV immunization
The same HPV vaccine formulation must be used to complete the series
the recommended dosing schedule depends on the age of the patient at vaccine initiation

35. Individuals initiating the vaccine series before 15 years of age
Two doses of HPV vaccine should be given at 0 and at 6 to 12 months.
Individuals initiating the vaccine series at 15 years of age or older
Three doses of HPV vaccine should be given at 0, 1 to 2 (typically 2), and 6
Immunocompromised patients
Three doses of HPV vaccine should be given at 0, 1 to 2, and 6 months regardless of age.
Less than 15: If the second dose was administered less than five months after the first, the dose should be repeated a minimum of 12 weeks after the second dose and a minimum of five months after the first.
Older than 15: months.The minimum intervals between the first two doses is four weeks, between the second and third doses is 12 weeks, and between the first and third dose is five months. If a dose was administered at a shorter interval, it should be repeated once the minimum recommended interval since the most recent dose has passed.

36. EFFICACY
Efficacy for preventing CIN2 or more severe disease due to HPV vaccine types was % in HPV naïve populations
44 percent among the overall population
the same among women who received the 9-valent vaccine and those who received the quadrivalent vaccine
efficacy of the 9-valent vaccine for preventing CIN2 or more severe disease, VIN2 or 3, and VaIN2 or 3 associated with HPV types 31, 33, 45, 52, and 58 (the types not contained in the quadrivalent vaccine) was:97 percent among the HPV-naïve population

37. preventing vulvar and vaginal condylomata
100 percent among HPV-naïve participants (without evidence of HPV vaccine types at enrollment)
70 to 78 percent among the overall population (with or without HPV infection at enrollment)
double-blind trial involving 5455 women between the ages of 16 and 24 years, we assigned 2723 women to receive vaccine and 2732 to receive placebo

38. in countries such as Australia that have achieved vaccination rates >70 percent, there has already been a 38 percent reduction in high grade dysplasia
Reductions in cervical disease have also been observed where vaccine uptake has been suboptimal
in a study from New Mexico where vaccine uptake ranged from 17 to 40 percent, the incidence of CIN continually decreased among females aged 15 to 19 years between 2007 and 2014 (10 and 40 percent reduction annually for CIN2 and CIN3, respectively)

39. Safety
no increased risk of Guillain-Barré Syndrome compared with other vaccines in similar age groups
Most common side effect is mild injection site reaction (may be higher with 9-valent)
Other possible reactions: syncope, headache, fever, dizziness
Anaphylaxis: in the US, only 10 cases met predefined criteria for anaphylaxis; the overall risk ratio was 0.1 case per 100,000 doses distributed

41. Behavioral Impact
Studies have not supported an increase in risky sexual behavior following vaccination
retrospective study of preteenage girls enrolled in a large health care system, the combined incidence of pregnancy testing, chlamydia testing, and contraception counseling was determined among those girls who did (n = 493) and did not (n = 905) receive at least one HPV vaccine dose
After adjustment for baseline health care utilization, race, and socioeconomic status, HPV vaccination was not associated with an increased rate of these sexual activity-related outcomes