Curious about what’s new in cervical cancer research? Join Dr. Evelyn Cantillo, gynecologic oncologist at Weill Cornell Medicine, as she shares the latest updates from the Society of Gynecologic Oncology (SGO) 2023 Annual Meeting on Women’s Cancer. Dr. Cantillo will also highlight what the research presented at the conference means for you and answer your questions about the new developments.

1. Report Back from SGO:
What’s New in Cervical Cancer
Evelyn Cantillo MD, MPH
Assistant Professor
Division of Gynecologic Oncology
Weill Cornell Medicine
Obstetrics and Gynecology

2. Disclosures
• I have nothing to disclose

3. By the
numbers
• Cervical cancer is the third most common
gynecologic cancer diagnosis and cause of
death among gynecologic cancers in the
United States
• In the United States, approximately 14,000
new cases of invasive cervical cancer and
4300 cancer-related deaths occur each year.
• In some parts of the world that are considered
resource poor, cervical cancer is the leading
cause of cancer-related mortality among women
• 75% decrease in the occurrence and death
from cervical cancer over the past 50 years
with the advent of screening programs

4. Let’s talk HPV
• HPV is a common virus that is passed on through
skin-to-skin contact.
• It infects the skin and any moist membrane like cervix
and throat. It is sexually transmitted.
• HPV is classified into low and high risk.
• Low-risk types cause genital warts
• High-risk types cause virtually all cases of cervical cancer.
In particular, high-risk HPV 16 accounts for approximately
50% of cases and HPV 18 for 20%.
• HPV vaccines are highly effective
• More than 98% of recipients develop an antibody
response
• recommended at 11 to 12 years-old
• If vaccinated before exposure to virus, the HPV vaccine
is 97% effective in preventing precancerous and
cancerous changes in the cervix

5. The problem
• Non-Hispanic Black (NHB) and
Hispanic/Latina women are more
likely than Non-Hispanic White
women to receive a diagnosis of and
to die of cervical cancer
• Reasons are multifactorial
• Expanding access to care and
improving the quality of services
rendered for uninsured patients and
those covered by Medicaid may
mitigate the known inequities in
cervical cancer diagnosis and related
outcomes

6. Closing the racial disparity gap in cervical cancer incidence and
mortality in the United States: The potential impact of screening and
vaccination
• To evaluate trends in prevention, screening, and incidence and mortality of cervical cancer among
racial/ethnic groups in the United States
• From 2001-2018, 230,106 patients were diagnosed with cervical cancer
• In 2001, Compared to White patients, the incidence of cervical cancer was 86% higher in Black patients and 90% higher in
Hispanic patients
• in 2001, Compared to White patients, cervical cancer mortality was 134% higher in Black patients and 43% higher in
Hispanic patients
• Incidence decreased by 2.48% annually in Black patients and 3.02% annually in Hispanic women but remained stable in
White patients.
• After 18 years, the incidence difference has narrowed to 42% higher in Black patients and 31% higher in Hispanic patients
• After 18 years, the mortality difference has narrowed to 91% higher in Black patients and 17% higher in Hispanic patients
• Using TeenVax data, in 2018, the proportion of adolescents receiving HPV vaccination was 54.2% in
White, 60.6% in Black, and 61.7% in Hispanic patients
• Over the last two decades, data showed a significant reduction in racial disparities in cervical cancer
incidence and mortality. Given that screening rates have remained relatively unchanged, the increase
in HPV vaccination rates may have contributed to these promising trends

7. Facilitators to cervical cancer screening in a
minority, urban, underserved population
• Study aimed to assess self-reported facilitators to cervical cancer screening among a
predominantly urban Hispanic population, who presented to a no-cost, community-based
screening clinic, to optimize outreach and care in this population
• Of the 79 patients assessed, 24.1% reported a history of abnormal cervical cancer
screening and 2 had never been screened; 92.4% had not received the HPV vaccine
• The most frequently reported single facilitator for patients was the receipt of
encouragement from a family member or friend (31.9%)
• 12.5% of patients reported the proximity of the clinic to their house as a facilitator
• Identifying facilitators among patients who successfully present to cervical cancer
screening is critical to designing care plans to reach all populations
• Survey showed that the single greatest facilitator to patients successfully presenting for
cervical cancer screening was the encouragement of a family member or friend

9. Management by Stage
• Refers to tumors 4cm or smaller
• Treatment: Surgery
Early Stage
(Stage IA1-IB2)
• Refers to tumors >4cm, involves upper vagina/pelvic
sidewall, pelvic lymph nodes+, or invades bladder/rectum
• Treatment: Primary chemoradiation
Locally Advanced
(Stage IB3-IVA)
• Refers to spread other parts of the body such as liver,
lungs, lymph nodes in the neck
• Treatment: systemic chemotherapy
Metastatic (Stage
IVB)

10. Locally
Advanced
Cervical
Cancer

11. Locally
Advanced
Cervical
Cancer
Where are
we?

12. Chemoradiation
5 cycles of weekly chemo given during
~5-6 weeks of external radiation
Followed by Brachytherapy (internal)

13. Outback Trial
• Question: would adding chemotherapy after
chemoradiation impact survival?
• phase III OUTBACK trial- a multicenter, international
randomized controlled trial-enrolled patients with
LACC
• 919 pts randomly assigned between April 2011 and
June 2017 to receive standard cisplatin-based
chemoradiotherapy (n=456) or standard cisplatin-
based chemoradiotherapy followed by four cycles of
carboplatin and paclitaxel (n = 463)
• 5-year overall survival was 72% in Arm 2 and 71% in
Arm 1
• Carboplatin and paclitaxel chemotherapy given after
standard cisplatin-based chemoradiotherapy for
unselected locally advanced cervical cancer increased
short-term toxicity and did not improve overall survival

14. Immunoth
erapy
• The majority of cervical cancers
express the programmed cell
death ligand 1 (PD-L1)
• helps to suppress the host
immune response
• Immunotherapy (IO) has emerged
as a promising therapeutic
option
• Can be PD-1 or PD-L1
inhibitors
• Aka checkpoint inhibitors
• Takes advantage of a
person's own immune
system to fight cancer
Image Credit: pharmaceutical-
journal.com

15. Chemoradiation and
pembrolizumab for
locally advanced cervical
cancer (Duska et al)
• Randomized Phase II trial to determine the safety and estimate the
immunologic effects of the combination
• 96 patients evaluated: arm 1(n=49) and arm 2(n=47).10.6% were Hispanic
and 17% were Black, the mean age=48 years
• At 3 months, In arm 1, there were 20 (43%) CR, 20 (43%) PR, and 6 (15%)
PD. In arm 2, there were 19 (44%) CR, 23 (54%) PR, and 1(2%) PD
• The results of this study support the safety and feasibility of adding
pembrolizumab to pelvic CRT concurrently or sequentially

16. Atezolizumab (atezo) Before and/or With Chemoradiotherapy in
Immune System Activation (Zamarin et al)
• 36 patients with pelvic or para-aortic lymph node–positive, LACC
receive either atezo prior to and concurrently with chemoradiation
(arm A) or atezo only concurrently with chemoradiation (arm B).
• Arm A: atezo 21 days before and on day 0 and 21 of chemoradiation
• Arm B: atezo on days 21 and 42 of chemoradiation
• 79% of patients in arm A vs 59% of the patients in arm B (P = .28)
experienced a 2-year disease-free survival
• Additionally, among the 31 patients with posttreatment biopsy data
collected after 28 days, those in arm A had a 69% pathologically
complete or partial response to treatment compared with 40% of
those in arm B
• This information warrants further clinical studies navigating
differential sequencing of chemoradiation and immune checkpoint
[inhibitors]

17. Metastatic/
Recurrent
Where are
we?

18. Evolution
• GOG 240 (2009)
• Phase III randomized controlled trial
• Enrolled 452 patients with recurrent, persistent, or metastatic cervical cancer
• Studied whether intravenous chemotherapy with or without
bevacizumab (an antiangiogenic agent) improves overall survival
• Regimens administering bevacizumab demonstrate significant
improvement in OS: 16.8 vs 13.3 mos (HR 0.77; p=0.0068) and
progression-free survival (HR 0.68; p=0.0002).
*SOC: IV chemotherapy+bevacizumab*

19. Evolution
• On October 13, 2021, the FDA approved pembro (Keytruda) in combination with
chemotherapy, with or without bevacizumab, for patients with persistent,
recurrent, or metastatic cervical cancer with PD-L1 tumor expression
• Keynote 826: of the 548 patients that had a PD-L1+ tumors, the median progression-free
survival (PFS) was 10.4 months in the pembro group vs 8.2 months in the placebo group
(P <.001)
• The overall survival (OS) rate was 53.0% at 24 months in the pembro group and 41.7% in the
placebo group
• The FDA also granted regular approval for pembro as a single agent in recurrent
or metastatic cervical cancer with disease progression on or after chemotherapy
with tumors expressing PD-L1
• Keynote 158: In PD-L1+ tumors, 2 women had their tumors disappear completely (CR) and
nine had their tumors shrink by 30% or more (PR) for an overall response rate of 14.3%.
• In 10 of the 11 women who responded to pembro, the responses lasted 6 months or longer

20. Evolution
• On September 20, 2021, tisotumab
vedotin-tftv, an antibody drug conjugate
or ADC, was granted accelerated
approval for the treatment of adults
with recurrent or metastatic cervical
cancer who have had disease
progression on or after chemotherapy
• A CR or PR was seen in 24% of patients
with CR in 7%

22. Toripalimab
Combined With
Chemotherapy and
Bevacizumab as
First-Line Treatment
in Patients With
Advanced Cervical
Cancer
• enrolled patients with refractory, recurrent or
metastatic cervical cancer who received no
prior systemic treatment for
recurrent/metastatic disease
• Unable to undergo radical treatment
• Concurrent chemoradiotherapy with cisplatin
once weekly x 5 weeks, radiotherapy (external
x 5-6wks followed by internal) and toripalimab
on days 1, 22 and 43
• objective response rate (ORR) of 77.3%
• Combination therapy elicited “promising”
responses in patient population

23. Conclusions
• The HPV vaccine is highly effective in
preventing precancerous and cancerous
changes in the cervix
• Family advocacy can make a difference
• Addition of immunotherapy in initial
treatment of locally advanced cervical cancer
• Recurrent/Metastatic disease remains a
therapeutic need especially for PDL negative
tumors

24. References
• https://www.cdc.gov/cancer/cervical/statistics/index.htm. Accessed May 2023
• https://health.clevelandclinic.org/7-surprising-things-need-know-hpv-cancer/
• https://www.cdc.gov/vaccines/vpd/hpv/hcp/vaccines.html#:~:text=All%20HPV%20vaccines%20have%20been,with%20the%20vaccine%20types%20at
• Holt HK, Peterson CE, MacLaughlan David S, et al. Mediation of Racial and Ethnic Inequities in the Diagnosis of Advanced-Stage Cervical Cancer by Insurance Status. JAMA Netw Open. 2023;6(3):e232985.
doi:10.1001/jamanetworkopen.2023.2985
• Eakin C, Liao C, Penalosa P et al. Closing the racial disparity gap in cervical cancer incidence and mortality in the United States: The potential impact of screening and vaccination. Presented at: 2023 Society of
Gynecologic Oncology Annual Meeting on Women’s Cancer; March 25-28, 2023; Tampa, FL
• Higgason N, Nguyen L, Le Y, et al. Facilitators to cervical cancer screening in a minority, urban, underserved population. Presented at: 2023 Society of Gynecologic Oncology Annual Meeting on Women’s Cancer; March
25-28, 2023; Tampa, FL
• Mileshkin LR, Moore KN, Barnes EH, et al. Adjuvant chemotherapy following chemoradiotherapy as primary treatment for locally advanced cervical cancer versus chemoradiotherapy alone (OUTBACK): an international,
open-label, randomised, phase 3 trial. Lancet Oncol. 2023 May;24(5):468-482. doi: 10.1016/S1470-2045(23)00147-X. Epub 2023 Apr 17. PMID: 37080223.
• Duska LR, Scalici JM, Temkin SM, et al. A randomized Phase II study of chemoradiation and pembrolizumab for locally advanced cervical cancer. Presented at: 2023 Society of Gynecologic Oncology Annual Meeting on
Women’s Cancer; March 25-28, 2023; Tampa, FL
• Zamarin D, Deng W, Lankes H et al. Evolution of peripheral and tumor immune parameters as biomarkers of differential sequencing of immune checkpoint blockade and chemoradiotherapy in locally advanced cervical
cancer: An NRG Oncology/GOG Study. Presented at: 2023 Society of Gynecologic Oncology Annual Meeting on Women’s Cancer; March 25-28, 2023; Tampa, FL
• Tewari KS, Sill MW, Long HJ 3rd, et al. Improved survival with bevacizumab in advanced cervical cancer. N Engl J Med.2014;370(8):734-743. doi:10.1056/NEJMoa1309748
• Colombo N, Dubot C, Lorusso D, et al; KEYNOTE-826 Investigators. Pembrolizumab for persistent, recurrent, or metastatic cervical cancer. N Engl J Med. 2021;385(20):1856-1867. doi:10.1056/NEJMoa2112435
• Chung HC, Ros W, Delord JP, Perets R, Italiano A, Shapira-Frommer R, Manzuk L, Piha-Paul SA, Xu L, Zeigenfuss S, Pruitt SK, Leary A. Efficacy and Safety of Pembrolizumab in Previously Treated Advanced Cervical Cancer:
Results From the Phase II KEYNOTE-158 Study. J Clin Oncol. 2019 Jun 10;37(17):1470-1478. doi: 10.1200/JCO.18.01265. Epub 2019 Apr 3. PMID: 30943124.
• Coleman RL, Lorusso D, Gennigens C, et al; innovaTV 204/GOG-3023/ENGOT-cx6 Collaborators. Efficacy and safety of tisotumab vedotin in previously treated recurrent or metastatic cervical cancer (innovaTV 204/GOG-
3023/ENGOT-cx6): a multicentre, open-label, single-arm, phase 2 study. Lancet Oncol. 2021;22(5):609-619. doi:10.1016/s1470-2045(21)00056-5
• https://www.nccn.org/professionals/physician_gls/pdf/cervical.pdf . Accessed May 2023
• Peng P, Yao H, Liu D, et al. Toripalimab combined with bevacizumab and chemotherapy for refractory, recurrent or metastatic cervical cancer: preliminary results of a single-arm, open-label, phase II trial. Presented at:
2023 Society of Gynecologic Oncology Annual Meeting on Women’s Cancer; March 25-28, 2023; Tampa, FL