Cervical Cancer Screening and Prevention

Today we discuss one of the basic screening tools of the OB-GYN office: the Pap smear. Named for Georgios (George) Papanikolau, credited for its creation around 1923, it is a test that has singlehandedly changed the face of cancer screening. With its widespread use, the incidence of cervical cancer in the US has dropped from 14.8 / 100k women in 1975, to 6.7 / 100k women in 2011. The converse also demonstrates the importance of this routine test: 50% of those diagnosed with cervical cancer have never had Pap screening, and 10% have not had screening within the preceding 5 years.

We also now know and can test for the presence of oncogenic strains of human papilloma virus, or HPV. Types 16 and 18 account for over 70% of cervical cancer worldwide, and 12 other strains account for the remaining majority of cases. Ongoing trials are looking at whether HPV screening may ultimately supplant cytology as the preferred 1st test, but HPV screening has added another excellent tool to help OB-GYNs discuss risk and prevent cancer in their patients.

Follow along with ACOG PB 168!

So what are the screening guidelines?
In the immunocompetent patient, they are as follows:

  • < 21 years: Screening should not be performed, even in the presence of behavior-related risk factors.

    • Only 0.1% of cervical cancer cases occur before age 20.

    • Women younger than 21 with no immunocompromising conditions generally clear HPV infection between 8-24 months after exposure. 

    • This population should have discussion about safe sex practices to avoid exposure to STIs including HPV, and strong consideration for HPV vaccination.

  • 21 - 29 years: Screening should be performed using cytology alone every 3 years.

    • Annual screening is discouraged in this group, as it exposes patients to a much more significant number of unnecessary procedures for minimal improvement in outcomes. 

    • HPV co-testing is not recommended in this group; however, HPV reflex testing in the event of an ASC-US Pap smear may be considered to determine need for colposcopy.

  • 30 - 65 years: Screening should be performed with cytology alone every 3 years, or cytology with HPV co-testing every 5 years. 

    • In this population, with a negative cytology and negative HPV test, the risk of developing CIN 2 or 3 in the next 4-6 years is extremely low, based on large database studies (approximately 0.08% risk over 5 years). The risk is higher, but also quite low, with cytology alone (0.26% over 5 years). This is the rationale for the screening interval being extended.

    • RCTs have demonstrated in this population that cotesting has a number of distinct advantages:

      • Cotesting has a higher detection rate of high-grade dysplasia in first round of screening, and decreases risk of CIN3 or cancer in subsequent screening.

      • Cotesting likely has a better pickup rate for cervical adenocarcinomas (vs. squamous cell) than cytology alone.

  • > 65 years, or post-benign hysterectomy: Screening should be discontinued, provided that:

    • There has been no history of CIN2, CIN3, or AIS in the preceding 20 years, and:

    • There are adequate negative prior results:

      • 3 consecutive negative cytology results within last 10 years, or

      • 2 consecutive negative cotest results within the last 10 years, with the most recent test performed within the past 5 years.

    • Women in this age group do get cervical cancer; however, the majority of these cases occur in women who are not screened, or in those who are underscreened.

    • The changes of menopause may also cause false positive Pap tests in this group, leading to likely unnecessary additional and invasive testing and procedures.

Behavioral risks, such as cigarette smoking, new or multiple sexual partners, or early sexual debut, may increase risk of HPV acquisition or persistence, but do not alter screening recommendations.

However, two particular conditions do merit changes to screening:

  • In utero diethylstilbestrol (DES) exposure:

  • DES was an estrogen that was manufactured and prescribed in the US during the 1930s until 1971. It was thought that the medication helped with premature birth or history of miscarriage, though by the 1950s it had been demonstrated to be ineffective.

  • ACOG states that annual cytology is reasonable in women exposed to DES in utero, as cohort studies have demonstrated a much higher incidence of clear cell adenocarcinoma of the vagina in women born to mothers who took DES or similar medications. DES has also been associated with other health problems in both men and women.

  • You can find a list of DES and related medications online at the CDC, and there is an interactive tool for patients to use to determine if they may be at risk.

  • HIV or immunocompromising conditions:

    • Women infected with HIV or with other immunocompromising conditions are less readily able to clear HPV infections. Thus, the recommendations in this population differ:

  • Screening should begin within 1 year of sexual activity, and no later than age 21.

  • In women less than 30, If the first screen is negative, it should be repeated in 12 months. If three consecutive annual screens are normal, screening may be spaced to regular intervals (i.e., q3 year cytology). HPV cotesting is not recommended.

  • In women older than 30, three annual tests should be normal, before moving to cytology alone or co-testing. Screening intervals should be every 3 years in this population, regardless of the method chosen. 

  • Screening should continue for the lifetime of the woman, and not stop at age 65.

What about HPV vaccination?

HPV vaccination has been an incredible advance for primary prevention of cancer. Currently available include a bivalent vaccine, a quadrivalent vaccine, and a 9-valent vaccine. All of these cover HPV types 16 and 18. The 9-valent vaccine covers up to 50% additional cases of cervical cancer versus the bivalent vaccine. The 9-valent vaccine should be given to boys and girls ages 9-26. 

  • For those receiving their first dose before age 15, only two doses given 6 months apart are needed. 

  • For those receiving it after age 15, 3 doses given at 0, 1-2, and 6 months apart are recommended. 

HPV vaccination is not recommended during pregnancy, but also hCG screening is not necessary prior to initiating the dose. If pregnancy interrupts the schedule, it should be resumed postpartum without need for redosing. Studies are ongoing to determine the safety of HPV vaccination during pregnancy. 

In June 2019, the CDC’s advisory council on immunization practices (ACIP) updated its HPV vaccination recommendations, to extend recommendation for vaccination for all persons up through age 45, after the FDA approved this in October 2018. While this hasn’t made it into official ACOG practice guidance yet, it’s safe to say that this is forthcoming!

Further Reading from the OBG Project:

USPSTF Releases Final Cervical Cancer Screening Guidelines – Including ‘HPV Only’ Option
Screening for Cervical Cancer in the Woman at Average Risk
What is the Most Efficient Method for Cervical Cancer Screening?
Cervical Cytology and HPV Screening in the HIV Positive Woman

Cervical Cancer Screening Strategies and Cost-Effectiveness: Which is the Best?

Vaccines II: MMR, Varicella, and HPV

Let’s tackle the second part of our vaccinations series with some of the more common live-virus vaccines: MMR, Varicella, and HPV. Check out the CDC vaccine guides linked here.

MMR

  • Measles, mumps, and rubella - all are live attenuated strains of the virus

  • Should NOT be given during pregnancy

  • Immunity is about 97% against measles and rubella after 2 doses, and 88% against mumps after 2 dose

  • Given ideally before pregnancy to protect against congenital rubella

    • Otherwise, after pregnancy and not during

    • This is because during pregnancy, the adaptive immune system is not as robust as when one is not pregnant and higher risk of the live attenuated virus actually causing disease.

      • If an adult is not immune to MMR (and we screen for rubella during pregnancy), at least one dose should be given postpartum.

  • Ingredients

    • Chicken embryo cell culture - medium

    • Human diploid lung fibroblasts - medium

    • Vitamins, amino acids, sucrose, glutamate, human albumin, sorbitol, gelatin, sodium phosphate, sodium chloride

    • Fetal bovine serum - medium

    • Neomycin - antibiotic

  • Side effects

    • Can get rash, temperature, loss of appetite 2-3 days

    • Can get a VERY mild form of measles or mumps

    • Extremely rare: severe allergic reaction

Varicella

  • Protects against chickenpox and shingles

    • 88-98% effective at preventing varicella after two doses, and 85% effective after 1 dose.

    • Ideally given before pregnancy to protect against chickenpox complications during pregnancy (ie. pneumonia) and congenital varicella syndrome or neonatal varicella.

    • Don’t give it during pregnancy.

  • Ingredients

    • Human diploid cells with DNA and protein

    • Sucrose, gelatin

    • Sodium chloride, monosodium-glutamate, sodium phosphate, potassium phosphate, potassium chloride, EDTA

    • Neoomycin

    • Fetal bovine serum

  • Side effects

    • Common: sore arm, fever, mild rash, temporary pain and stiffness

    • Severe: (very uncommon) - severe infection, pneumonia

HPV

  • Gardasil 9 protects against human papilloma virus 16, 18 (causes 80% of cervical cancer cases), 6, 11 (90% of genital wart cases), and another 5 types (31,33,45, 52, 58) that can lead to cervical cancer.

    • 3 separate shots for people aged 15-45 - high efficacy, with close to 100% prevention of HPV virus

    • If 9-14, 2 shots are sufficient

    • Not currently recommended during pregnancy

      • Good time to give it: immediately pp in hospital (dose 1), then 6 weeks pp  

  • Ingredients

    • Vitamins, amino acids, mineral salts, carbohydrates

    • Amorphous aluminum hydroxyphosphate sulfate

    • Sodium chloride

    • Polysorbate 20

    • Neomycin, yeast protein

  • Side effects

    • Common: pain, redness, swelling of arm where shot was given

    • Less likely: fever, headache, feeling tired, nausea, muscle or joint pain.