Cervical Cancer During Pregnancy: A Multidisciplinary Approach to a Complex Oncological Case

Abstract

Background: Cervical cancer is the fourth most common malignancy among women, posing significant diagnostic and therapeutic challenges during pregnancy. Case presentation: This case report presents the treatment of a 32-year-old pregnant woman diagnosed with cervical cancer. Following the diagnosis at 7 weeks of gestation, histological and imaging examinations were performed, leading to the initiation of neoadjuvant chemotherapy. Due to the tumor progression noticed under therapy, cesarean section was performed at 29 weeks, immediately followed by radical hysterectomy. Conclusions: The management of cervical cancer during pregnancy necessitates a multidisciplinary approach, based on the patient’s condition, tumor stage, and fetal maturity. This case highlights the limitations and complexities of treating cervical cancer during pregnancy and emphasizes the importance of individualized oncological and surgical planning.

1. Introduction

Cervical cancer is the fourth most common malignant tumor in women, accounting for approximately 6% of all female cancers [1,2,3]. This neoplasia is most often associated with high-risk human papillomavirus (HPV) types, particularly types 16 and 18 [4]. The persistent presence of the virus promotes the malignant transformation of cervical epithelial cells, which leads to the development of invasive cancer over years or even decades. Cytological and HPV screening enables the early detection of cervical neoplastic conditions, often identifying them at a precancerous stage, or when cancer is present at an early stage [5]. The treatment outcomes of early-recognized tumors are favorable; however, at advanced stages, the prognosis of the disease significantly worsens. Depending on the stage, the treatment strategy encompasses a broad spectrum, ranging from surgical interventions to radiotherapy, chemotherapy, and even targeted oncological therapies [6].

Cervical cancer during pregnancy is rare, with an incidence of 0.44–5.08 cases per 100,000 pregnancies, accounting for approximately 3% of all cervical cancer cases. The incidence is increasing globally, likely due to the trend toward delayed childbearing [7]. When cervical cancer is diagnosed during pregnancy, several factors must be taken into account, including the tumor stage, gestational age, and the potential impact of treatment on the pregnancy. Evaluating how the chosen therapeutic approach may affect the fetus is essential. Decision-making involves numerous medical and ethical considerations, posing a complex challenge for the multidisciplinary team. Consequently, treatment plans must be individualized, carefully balancing the expected benefits and risks while considering the patient’s preferences. Beyond the standard members of the tumor board, at a minimum, the maternal and fetal care teams, the family, and, when necessary, additional specialists should be involved in the decision-making process.

2. Detailed Case Description

Below, we describe the medical history of our patient diagnosed with cervical cancer during pregnancy. Our patient was treated in close collaboration with the Hungarian National Institute of Oncology and the Department of Obstetrics and Gynecology at Semmelweis University.

Our patient is a 32-year-old primigravida without significant comorbidities in her medical history, apart from her class I obesity (BMI of 34.4 kg/m²) and her known insulin resistance, which was controlled by dietary interventions throughout her pregnancy.

At the seventh week of gestation, following a positive pregnancy test in May 2024, the patient underwent a gynecological examination. Speculum inspection revealed an irregular, friable lesion of the cervix, while bimanual palpation confirmed cervical induration. A cervical cytological smear was obtained during the same visit. Notably, the patient had a previous cervical cytology showing atypical squamous cells—cannot exclude HSIL (ASC-H). The cytological findings were indicative of glandular epithelial malignancy. In light of this result, the patient underwent a diagnostic cervical excision. The excised specimen measured approximately 5 mm in diameter. Histopathological examination revealed poorly differentiated (grade 3), HPV-associated squamous cell carcinoma with no proof of lymphovascular space invasion (LVSI). Essentially, all the tissue excised consisted of tumor cells only, which raised concern for residual disease.

To establish the extent of the disease, a pelvic MRI scan was performed that confirmed the presence of a tumor. The lesion, with a maximal diameter of 30 mm, was limited to the cervix as the pericervical fascia was intact, and no signs of parametrium involvement were noticed. The MRI did not reveal any pathological lymph nodes, suspicious for metastases; however, due to the limited sensitivity of imaging in excluding lymph node involvement, the multidisciplinary tumor board (MDTB) of the National Institute of Oncology recommended a robot-assisted sentinel lymph node biopsy and bilateral pelvic lymph node dissection. According to the guidelines, an ultrastaging assessment of the sentinel lymph nodes was performed, and the histological examination of the 28 removed lymph nodes confirmed the absence of cervical cancer metastasis.

The patient was counseled extensively regarding the diagnosis and possible management pathways. Following the availability of histopathological results, the MDTB reached a final decision after 12 weeks of gestation. The patient clearly expressed her wish to preserve the pregnancy, provided it would not significantly compromise her long-term prognosis. After multidisciplinary consultation, and in light of the absence of lymph node involvement and favorable imaging, a conservative approach was agreed upon. At this point, the patient was 16 weeks pregnant; therefore, the MDTB recommended neoadjuvant chemotherapy consisting of a combination of 350 mg paclitaxel and 600 mg carboplatin (AUC 5) every 3 weeks.

After 3 cycles of chemotherapy, in line with the previous MDTB recommendation, an interim MRI was performed to assess the effectiveness of the treatment. While no metastasis was detected, tumor size progression was confirmed: the tumor grew from a previous maximal diameter of 30 mm to 48 mm (Figure 1).

Based on the repeated MDTB decision, for oncological safety, preterm delivery by cesarean section followed by radical hysterectomy was recommended, due to the progression of cervical cancer despite oncological treatment.

Considering the gestational age and the expected need for neonatal intensive care due to prematurity, the patient’s treatment continued at the Department of Obstetrics and Gynecology, Semmelweis University. Following both perinatological consultations with neonatologists and antenatal fetal lung maturation, cesarean section and simultaneous radical hysterectomy were performed in the 29th gestational week.

The newborn weighted 1280 g at delivery and had Apgar scores of 8/9. After birth, non-invasive respiratory support was required. A chest X-ray performed during intensive care confirmed respiratory distress syndrome for which surfactant therapy was administered along with empirically initiated prophylactic antibiotic therapy. Pneumothorax developed in the left lung, which required drainage for 3 days and subsequently resolved (Figure 2).

The neonate was admitted to the NICU due to prematurity. The initial course required non-invasive respiratory support for five days and parenteral nutrition for the first seven days, after which a full transition to enteral feeding was achieved progressively. After achieving oral feeding, it remained uninterrupted, although breastfeeding could not be initiated due to the lack of milk production. Besides pneumothorax, which was managed appropriately, no other major complications such as intraventricular hemorrhage, necrotizing enterocolitis, or sepsis occurred. At discharge, the infant weighed 2090 g and was feeding independently. Subsequent follow-up visits up to six months of corrected age showed age-appropriate neurodevelopmental progress, without evidence of motor delay, growth restriction, or neurosensory impairment.

The histopathological examination of the surgical specimen removed during radical hysterectomy (Figure 3) confirmed that the tumor was HPV-associated, though based on its morphology and immunophenotype it was diagnosed as HPV-associated carcinoma with features suggestive of an adenosquamous carcinoma, though a purely squamous morphology could not be excluded. The tumor demonstrated a predominantly solid morphology with focal cystic areas (Figure 3A). Squamous cells (Figure 3B) and intermediate cells (Figure 3C) were also visible. Some of the squamous cells had abundant clear cytoplasm. Scattered gland-like spaces with flattened epithelium contained PAS-D-positive mucin, which appeared largely extracellular/interstitial (Figure 3D). Highly atypical tumor giant cells were also seen. The mitotic count was elevated; abnormal mitoses were present. A marked inflammatory infiltrate was present within the tumor stroma, mainly composed of an unusually high number of eosinophilic granulocytes (Figure 3E). Immunohistochemistry revealed p63 and p40 positivity within squamous cells. The tumor exhibited diffuse intranuclear and intracytoplasmic immunoreactivity for p16 (Figure 3F). The p53 immunohistochemistry demonstrated a wild-type expression pattern. Next-generation sequencing was not performed.

The maximum extent of the tumor was 65 mm craniocaudally and 42 mm latero-laterally. The tumor was also present in the outer third of the cervical stroma, but no parametrial infiltration was observed.

Lymphovascular invasion was identified only in three foci. There was no involvement of the lower uterine segment, the vaginal wall, or parametrial tissues. The tumor did not infiltrate the vaginal wall, the lower segment of the uterus, the uterine mucosa, the myometrium, the surrounding connective tissues, or other organs.

Surgical margins were tumor-free, and the three lymph nodes identified in the removed parametrium were also free of cancer (Figure 4). No distant metastases were detected during surgery.

Postoperatively, spontaneous milk production did not begin; therefore, lactation suppression was not necessary.

Considering the tumor progression observed during chemotherapy and the histopathological findings, particularly the tumor grade, size, depth of stromal invasion, and lymphovascular involvement, the disease was classified as intermediate risk. Therefore, as per the decision of the Gynecologic Oncology Committee at Semmelweis University, adjuvant radiochemotherapy was recommended, with external beam radiotherapy (EBRT) in 25 fractions, with a total dose of 50.4 Gy.

3. Discussion

Cervical cancer remains a significant global health issue, primarily driven by persistent infection with the high-risk HPV strains, especially types 16 and 18 [8]. Although early detection through cytology and HPV screening has improved outcomes, advanced-stage disease still poses serious challenges. During pregnancy, cervical cancer is rare but increasingly encountered, largely due to delayed childbearing. In such cases, treatment decisions must balance maternal oncologic safety with fetal well-being, often leading to complex clinical and ethical dilemmas for both the patient and the multidisciplinary care team.

This case report summarizes the oncological management of a pregnant woman diagnosed with cervical cancer. The case demonstrates the diagnostic and therapeutic difficulties encountered when dealing with tumors detected during pregnancy. Accurate histopathologic classification of the tumor is essential, particularly during pregnancy, as it directly informs decisions about timing and intensity of treatment while balancing maternal and fetal outcomes. There is a lack of clear guidelines and specific protocols to support decision-making, requiring case-by-case evaluation when establishing a treatment plan. Although some international guidelines offer general recommendations, many still advise individualized assessment [1,9]. In therapeutic decisions, along with the extent of the disease, gestational age and the response to any initiated treatment are equally crucial factors.

A review of the literature reveals that cervical cancer diagnosed during pregnancy, while rare, is increasingly encountered due to delayed maternal age at first pregnancy. A large multicenter cohort study by Amant et al. involving over 100 pregnant patients with cervical cancer emphasized that oncologic outcomes are not compromised when pregnancy is preserved under a carefully monitored and guideline-concordant management plan [9]. Other studies report variable outcomes based on tumor size, nodal status, and treatment modality. For example, neoadjuvant chemotherapy initiated during the second trimester has been associated with disease control rates of 66–85%, allowing prolongation of pregnancy until fetal maturity in a significant number of cases [10]. Conversely, in cases where progression occurs during chemotherapy, as seen in our patient, preterm delivery and immediate definitive treatment are necessary. A retrospective analysis by Sood et al. further highlighted the importance of avoiding vaginal delivery in these patients, as it was associated with a higher recurrence risk [11]. Taken together, current evidence reinforces the importance of individualized, multidisciplinary care, guided by disease stage, gestational age, and informed maternal choice.

The initial and most essential consideration following diagnosis is to engage the patient in a thorough discussion regarding her informed preferences about continuing the pregnancy. This conversation must take place before establishing a definitive treatment strategy. Following this, the extent of the disease, the gestational age, and the feasibility of any oncologic treatment or surgical intervention can be assessed in light of the patient’s preferences and values.

The diagnostic steps for cervical cancer and its precursors are the same as for non-pregnant patients: exfoliative cytology, HPV typing, and biomarker testing all contribute to diagnosis. If high-risk abnormalities are found, colposcopy, followed by the biopsy of the cervix, is necessary. Surgical interventions of the cervix during pregnancy are only recommended if colposcopy suggests an invasive disease, due to higher associated risks.

For staging of cervical cancer in non-pregnant patients, contrast-enhanced pelvic MRI, PET-CT, and expert pelvic examination are used. In contrast, during pregnancy, the diagnostic options are much more limited due to the risks of fetal exposure to radiation and medications. The pelvis can be safely examined with ultrasound during pregnancy, which has a sensitivity comparable to MRI. If expert ultrasound is not available, MRI without contrast agent is a viable alternative. For abdominal imaging, these two methods are also used. To exclude thoracic metastasis, CT can be safely performed, with proper patient positioning and shielding after weighing potential benefits and risks.

If there is macroscopic suspicion of an invasive tumor, and imaging suggests that complete removal is possible (meaning that the tumor size does not exceed 2 cm), complete removal by loop conization is recommended. Otherwise, only biopsy is suggested [12,13]. Clear-margin excision of cervical tumors may be sufficient for T1a1 and T1a2 squamous cell carcinoma, although in the latter case, if lymphovascular invasion is present, at least sentinel lymph node removal is necessary. For tumors less than 2 cm in diameter and in case of the absence of LVSI, this approach may be considered oncologically safe, as supported by recent evidence, and incorporated into the ESGO/ESTRO/ESP 2023 guidelines [1]. This is supported by the evidence from the SHAPE trial and the ConCerv study demonstrating that for patients with FIGO stage T1a2 and T1b1 cervical cancer, less radical surgical approaches—such as simple hysterectomy or even conization—can be an option. The findings of these studies have subsequently been integrated into contemporary clinical practice guidelines, supporting a shift toward de-escalation of surgical treatment in appropriately selected low-risk cases. (Figure 5).

However, the use of these procedures during pregnancy is not without risks. Complications can include bleeding (5–15%), spontaneous abortion (up to 25%), preterm birth, or rupture of membranes [14,15]. To reduce complications, some recommendations suggest performing a prophylactic cervical cerclage [16,17].

In addition to tumor size, lymph node status plays a decisive role in determining the prognosis of cervical cancer.

In the IB–IIA stages of the disease, the 5-year survival rate ranges between 88% and 95% in the absence of lymph node involvement, whereas it drops to 51–75% if lymph node metastasis is present [1].

Information about the condition of lymph nodes can be obtained through imaging methods, such as ultrasound and MRI. Some studies have explored the possibility of PET-MRI, but its safe and reliable application remains unclear based on current data [18].

If imaging examinations are negative, sentinel lymph node removal and histopathological analysis can further refine the diagnostics. This can be performed during the first two trimesters of pregnancy, as uterine size at that point still allows access to the pelvic lymph nodes. Sentinel lymph node biopsy may replace systematic lymphadenectomy, but only up to stage IB1. In our patient, this was the reason for both sentinel and pelvic lymph node removal being performed using a robot-assisted approach.

Tumors larger than 2 cm, pose the greatest therapeutic challenge. Treatment options must be separated depending on whether the patient wishes to continue the pregnancy or not.

If the continuation of pregnancy is not desired, in stages IB2, IB3, and IIA, radical hysterectomy is indicated, provided that the general surgical criteria are met. For stages above IIB, definitive radiochemotherapy is the recommended treatment [1] (Figure 6). Termination of pregnancy before 12 weeks is not justified; after that, termination must be performed via hysterotomy.

If the pregnant patient does wish to continue the pregnancy, the following alternatives may be considered. In very select cases of stage IB2, radical trachelectomy may be an option. However, the literature contains very few reports of such cases, not only because of the rarity of tumors larger than 2 cm during pregnancy, but also because the procedure is technically difficult and carries a high risk of miscarriage compared to simple conization [19,20,21].

For tumors larger than 2 cm, the choice of treatment depends primarily on the local spread and lymph node status. If imaging (expert ultrasound, pelvic MRI) confirms that the tumor is confined to the cervix, and no suspicious lymph nodes are seen in the pelvis, surgical determination of pelvic lymph node status is recommended. Sentinel lymph node biopsy alone is not sufficient based on available evidence. Complete pelvic lymphadenectomy is necessary, in addition to sentinel node biopsy [22,23,24,25,26,27].

As previously mentioned, this is feasible via a minimally invasive surgery up to the 14–16th weeks of gestation. This was performed in our case by using a robot-assisted technique. If the results show no metastatic lymph nodes (as in our case), continuation of pregnancy with the initiation of oncological treatment is possible. The goal of oncologic treatment is to stop tumor progression or ideally induce regression, allowing for pregnancy prolongation to a gestational age, where fetal maturity reduces the risks associated with prematurity [9].

If the tumor is beyond stage IB2 at diagnosis, another therapeutic alternative is to initiate neoadjuvant chemotherapy, which is only feasible from the second trimester onward. In this case, treatment must continue until fetal maturity, provided there is an adequate therapeutic response.

Chemotherapy carries specific risks during pregnancy. In the first trimester, the risk of developmental anomalies and miscarriage increases significantly [28].

Based on numerous prospective studies, platinum-based chemotherapy protocols (e.g., carboplatin or cisplatin, combined with a taxane such as paclitaxel or docetaxel) are recommended [29,30,31]. In our case, carboplatin was used to minimize fetal ototoxicity. Drug dosages during pregnancy are the same as for non-pregnant women. In cervical cancer, neoadjuvant chemotherapy can result in a response rate of 66–85% and pathological remission [10]. In the case of good therapeutic response, chemotherapy can be continued until fetal maturity, since every additional day helps to reduce the risks associated with prematurity. However, we must consider the fetal effects of chemotherapy as well, such as intrauterine growth restriction, premature rupture of membranes, or preterm birth. Prenatal care protocols should be adjusted accordingly.

In our presented case, unfortunately, chemotherapy did not deliver the expected results, and imaging during treatment confirmed disease progression, which justified delivery at a viable gestational age via cesarean section, followed by further radical treatment.

The largest cohort study on cervical cancer during pregnancy found that vaginal delivery was one of the most important predictors of recurrence. Therefore, a cesarean section is recommended in such cases. Vaginal delivery may be considered if the tumor has been completely removed by conization earlier [11]. In our case, after individual assessment, pregnancy was terminated by cesarean section in the 29th week, following fetal lung maturation and reaching a more advanced stage of fetal development.

Regarding radical surgical treatment, a type C1 radical hysterectomy was performed. However, based on the final histological features (deep stromal invasion, LVSI positivity, grade 3 differentiation, aggressive histotype) and the tumor’s aggressive, therapy-resistant behavior, adjuvant radiotherapy was also recommended for the patient.

While the initial strategy was to prolong pregnancy with neoadjuvant chemotherapy, the tumor showed progression despite this approach. Alternative strategies such as dose intensification or earlier surgical intervention, including fertility-sparing radical trachelectomy, have been explored in selected early-stage cases, particularly when tumor size is ≤2 cm and histological features are favorable [32]. However, in our case, the tumor measured 30 mm at diagnosis and subsequently increased to 48 mm during NACT, rendering fertility-preserving surgical options inappropriate. Additionally, given the gestational age and absence of lymph node involvement, the selected chemotherapy regimen prioritized fetal safety over maximal oncologic efficacy [33]. Nevertheless, this case underscores the need for further investigation into optimized NACT protocols and personalized surgical timing in pregnant patients with cervical cancer.

Importantly, neonatal follow-up through six months of corrected age revealed no evidence of neurodevelopmental impairment, and the infant demonstrated appropriate growth and neurologic function, supporting the safety of this management approach when preterm delivery is required for maternal indications.

4. Conclusions

The aim of our case report is to draw attention to the diagnostic and therapeutic difficulties and possible solutions for gynecological malignancies diagnosed during pregnancy, particularly that of cervical cancer. In such, and similar cases, it is especially important that the treatment plan is developed by a multidisciplinary medical team, in which a neonatologist also participates, in addition to the traditional members of the oncology board, for the case discussion.

When establishing a therapeutic plan in these special situations, a holistic approach and the involvement of the patient and her family in the therapeutic decision-making process are even more important than usual. Fortunately, the occurrence of the disease among pregnant women is low; therefore, it is particularly important that such patients are treated in centers specialized for this patient group, where adequate professional and infrastructural background is available for proper care and follow-up.

A multidisciplinary assessment and treatment, along with a thorough review of the available evidence-based literature, are essential for making the most appropriate, personalized decision.