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?

HIV in the Non-Pregnant Patient

We jump back to our STI saga to cover HIV today. ACOG PB 167 and CO 596 make for supplementary reading for this show.

The CDC and USPSTF recommend at least one-time HIV screening in most women. The CDC goes further to recommend up to annual screening in certain high-risk groups, including IV drug users, > 1 sex partner annually or known sex partner with HIV, those who exchange sex for money or goods, and MSM.

Screening is important, because almost 25% of new cases occur in women, and heterosexual intimate contact is the most common form of disease spreading. ACOG subscribes to a philosophy of “opt out” testing, by which HIV screening should be considered routine, with the patient able to opt out. Physicians need to document the reason for this in their notes. Screening tests are broken into rapid and confirmatory. A positive rapid screen should always be followed with a confirmatory test, as the rapid screens have high sensitivity, but lower specificity.

GYN care may vary somewhat with positive HIV status. For Pap smears, PB 167 describes an appropriate algorithm for dealing with initial screening and some positive results:

ACOG PB 167

ACOG PB 167

We spend some time reviewing the treatment of other STIs in the podcast briefly, all of which are reviewed in PB 167 as well. Highlights include:

  • Using 1 week rather than single-dose metronidazole treatment for trichomonal infections

  • Re-testing any positive GC/CT testing result at 3 months, due to high risk of re-infection

  • Screening for most STIs at entry to care for HIV-affected patients.

Birth control is also another important topic for HIV-affected patients. ACOG and the CDC recommend use of dual-contraception — that is, a barrier method and a hormonal method — to prevent viral spread. Certain forms of hormonal contraception may be affected by antiretroviral drugs:

  • CHCs: The NNRTI non nucleoside reverse transcriptase inhibitor efavirenz and certain protease inhibitors (-navir) may decrease efficacy of combined methods by reducing contraceptive hormone levels; however, they are considered US MEC Category 2.

    • The exception to this rule is fosamprenavir, as CHCs also lead to decreased levels of this protease inhibitor (US MEC 3).

  • Etonogestrel implant:  Similarly to CHCs, there are theoretical risks in decreased contraceptive effectiveness for patients on efavirenz; however, the implant remains US MEC 2.

  • DMPA: MEC category 1 for all users, except for those on fosamprenavir; there is limited evidence DMPA decreases fosamprenavir levels like CHCs (US MEC 2).

  • IUDs: MEC category 1 for all users!

  • Emergency contraception: for oral medicatons such as levenorgestrel and ulipristal, these should be offered to HIV-affected women as the benefits of emergency contraception are considered to outweigh the risks in this group. Similarly to CHCs, there is theoretical risk of decreased efficacy of these methods among women taking efavirenz.

Finally, in a preview to our next episode, we talk about preconception counseling for HIV-affected patients. The goal for any patient with HIV is to achieve a negative viral load, and for OB-GYNs, this is important to limit vertical transmission. Efavirenz has been associated with neural tube defects, so should be avoided in pregnancy if possible.

Conceiving is safest through artificial insemination. However, if natural conception is desired. OB-GYNs should discuss limiting unprotected intercourse to ovulatory times, and using pre-exposure prophylaxis for the patient, or her partner, in serodiscordant couples. This generally involves a daily regimen of tenofovir/emtricitabine (Truvada) for 1 month prior to, and 1 month after, conception. Risk reduction is estimated to be somewhere between 63-75%, and the best-available data suggests this is likely safe.