Challenges in managing cervical cancer in pregnancy: Three case reports

Abstract

Cervical cancer in pregnancy is a rare but increasingly recognised condition, affecting approximately 0.1–12.0 per 10,000 pregnancies annually. Symptoms such as vaginal bleeding, discharge, dyspareunia, and pelvic pain may overlap with normal pregnancy-related changes, often leading to delayed diagnosis. Speculum and bimanual examination is essential in pregnant women presenting with vaginal bleeding. Urgent colposcopy referral (for example, in the UK through the two-week wait pathway) is essential. Management strategies depend on cancer stage, gestational age, and patient preferences. Options include pregnancy termination with immediate treatment or consideration of neoadjuvant chemotherapy during pregnancy in women who wish to postpone definitive therapies until after delivery. Pelvic lymphadenectomy for staging is considered safe prior to 22 weeks of gestation. Neoadjuvant chemotherapy is contraindicated in the first trimester but may be administered safely later in pregnancy. Serial magnetic resonance imaging is valuable for monitoring tumour progression and informing treatment plans. This case series highlights the clinical and ethical complexities in managing cervical cancer in pregnancy and underscores the importance of specialist, multidisciplinary, and individualised care. Further research is necessary to develop standardised, evidence-based guidelines for this challenging clinical scenario.

Highlights

• •Cervical cancer is rare, affecting 0.1–12.0 per 10,000 pregnancies annually.
• •Vaginal bleeding warrants prompt speculum and bimanual examination.
• •Management depends on gestation, cancer stage, and patient preference.
• •Neoadjuvant chemotherapy is safe after the first trimester.
• •Multidisciplinary care is essential for optimal outcomes.

1. Introduction

Cervical cancer in pregnancy is rare but increasingly observed, affecting 0.1–12.0 per 10,000 pregnancies annually [1]. Persistent high-risk human papilloma virus (HPV) infection is responsible for over 99 % of cases [2]. Histological subtypes mirror those in the general population, with squamous cell carcinoma (SCC) comprising the majority [3]. Vaginal bleeding is the most common symptom; others include discharge, dyspareunia, and pelvic pain. These often overlap with normal pregnancy symptoms, contributing to diagnostic delays. Speculum (and if needed, bimanual) examination is essential in any pregnant woman presenting with bleeding [4]. Management depends on gestation, cancer stage, and patient preference, and may involve pregnancy termination with definitive treatment or neoadjuvant chemotherapy to delay treatment until postpartum. This case series explores the diagnostic and ethical complexities and highlights the need for specialist, multidisciplinary, and individualised care.

2. Case Series

2.1. Patient A

A 32-year-old woman at 36 + 1 weeks of gestation in her first pregnancy presented with 100 ml of antepartum bleeding. Speculum examination revealed an irregular cervical lesion. She had recently immigrated to the UK and had never undergone cervical screening. Colposcopy and biopsy confirmed a moderately differentiated keratinising cervical squamous cell carcinoma (SCC). Magnetic resonance imaging (MRI) showed a 2.8 cm FIGO stage IB1 lesion (Fig. 1). Following a multidisciplinary team (MDT) discussion, she received two doses of intramuscular betamethasone 12 mg and underwent a planned classical Caesarean section at 37 + 1 weeks with subsequent radical hysterectomy, bilateral salpingectomy, ovarian conservation, and pelvic lymphadenectomy (Fig. 2, Fig. 3). The delivery and surgery were performed jointly via a midline laparotomy by the obstetric and gynae-oncology teams. Both ovaries were transfixed above the pelvic brim and an omental spacer was created. The estimated blood loss was 600 ml. Her postoperative recovery was uneventful, and she was discharged on day 3.

Fig. 1.

Patient A: Sagittal magnetic resonance image demonstrating a cervical tumour originating from the anterior aspect of the cervix.

Fig. 2.

Patient A: Surgical specimen showing an exophytic cervical tumour and resection of the upper vagina following radical hysterectomy.

Fig. 3.

Patient A: Surgical specimen following radical hysterectomy and bilateral salpingectomies performed after a classical Caesarean section.

Histology confirmed a 40 mm SCC with a depth of invasion of 22 mm. The tumour exhibited multifocal lymphovascular invasion (LVSI) and infiltrated into the outer third of the cervical stroma. All the resection margins were clear and all pelvic lymph nodes were negative. Based on the tumour size, presence of LVSI, and stromal involvement (Delgado criteria), she was referred for adjuvant chemoradiotherapy, which she completed successfully. Five years after treatment, she remained disease free.

2.2. Patient B

A 37-year-old primigravida with an unremarkable antenatal course attended for labour induction at 39 + 5 weeks of gestation. She had been up to date with the cervical screening programme and had been clear. The pregnancy had been uncomplicated, with no obstetric or medical concerns noted during routine antenatal care. During the pre-induction vaginal examination, a firm, non-tender mass measuring approximately 3 × 3 cm was palpated over the anterior cervix. The lesion provoked bleeding on digital examination, raising concern for malignancy. Given the suspicious nature of the mass, the decision was made to proceed with an emergency Caesarean section. A healthy live infant was delivered with Apgar scores of 9 and 10 at 1 and 5 min. The maternal postoperative course was uneventful.

At the postnatal follow-up at two weeks, the patient was referred to the colposcopy clinic for further assessment. A biopsy confirmed the presence of a HPV-associated, non-keratinising, poorly differentiated invasive SCC. MRI revealed an exophytic lesion measuring 6.2 × 2.5 cm, originating from the anterior cervical lip and extending into the upper two-thirds of the vagina, with left parametrial invasion. A pathologically enlarged right external iliac lymph node was also identified. Positron emission tomography–computed tomography (PET-CT) imaging confirmed FIGO stage IIIC1 disease due to the presence of a PET-avid 16 mm right external iliac lymph node. The patient was referred for neoadjuvant chemotherapy, external beam chemoradiotherapy, and vault brachytherapy.

2.3. Patient C

A 38-year-old woman in her fourth pregnancy and 11 weeks of gestation was radiologically diagnosed with FIGO stage IB1 cervical SCC. She initially presented with postcoital bleeding and an examination revealed a 2 cm anterior cervical tumour. Her prior cervical screening history was not available. After counselling, she elected to terminate the pregnancy and undergo a radical hysterectomy with ovarian conservation. The radical hysterectomy was uneventful.

The histology showed a moderately differentiated SCC FIGO stage IB1 SCC of the cervix with a maximum horizontal length of 18.5 mm, deep stromal invasion and multifocal LVSI. She was referred for adjuvant chemoradiotherapy. She completed her adjuvant treatment and was followed up for two years and then discharged to her general practitioner. She declined the prescription of hormone replacement therapy due to a family history of breast cancer. She remained disease free after five years.

3. Discussion

3.1. Screening in Pregnancy

HPV-DNA testing is not routinely recommended for cervical cancer screening in pregnancy due to the high rate of inconclusive results [5,6]. In the first 4–8 weeks, physiological glandular hyperplasia and increased vascularity of the cervix and vagina are manifest [7]. These physiological changes result in mucus overproduction, hyperaemia and oedema and accentuate diagnostic challenges, including Pap smear and colposcopy, especially beyond 20 weeks. This is in addition to the inherent challenges of achieving an optimal cervical view during pregnancy [4,8]. Pap smear testing in pregnancy is associated with a higher degree of false positive results whereby decidual cells are mistakenly labelled ‘atypical’ and increase the rate of unnecessary referrals for colposcopy [8]. Psychological barriers to screening should also be considered; pregnant women may be reluctant to consent to these procedures due to a lack of information and fear of triggering obstetric complications [8].

Women of childbearing age and with a normal cervical smear history should attend for screening every three years. If their screening is due during pregnancy, these women should be advised to postpone their cervical smear until after delivery. However, screening can be considered in women who have never been screened or who have not attended for a cervical smear for over three years [8,9]. One study demonstrated that the majority of patients diagnosed with cervical cancer in pregnancy had never undergone Pap smear testing previously [10]. Routine Pap testing in pregnancy could particularly benefit at-risk populations who encounter obstacles to access screening, namely embarrassment, language barriers or logistical constraints [11].These considerations support growing evidence in favour of integrating routine cervical cancer screening into antenatal care [8,11]. Further research is required to evaluate its feasibility and cost-effectiveness prior to policy changes.

3.2. Diagnostic Challenges in Pregnancy

Bimanual and speculum examination is essential in pregnant patients presenting with bleeding, to determine its origin and expedite diagnosis [12]. Colposcopy is the most accurate diagnostic tool and is indicated following a positive Pap smear or in the presence of an abnormal cervix on visualisation. Colposcopists and pathologists must be highly experienced for accurate diagnosis, as pregnancy-associated endocervical glandular hyperplasia and histological changes can mimic those seen in invasive cervical cancer [4,11,13]. Directed biopsies are superficial and are not associated with an increased risk of spontaneous abortion or preterm delivery [14,15]. In contrast, a large loop excision of the transformation zone procedure (LLETZ) or loop electrosurgical excision procedure (LEEP), the standard intervention for cervical dysplasia or neoplasia, significantly increases the risk of maternal haemorrhage and preterm delivery when conducted beyond the second trimester [16]. These risks should be discussed with the patient, in conjunction with the obstetric team. In this case series, none of the three patients underwent a LLETZ or LEEP. Instead, MDT discussions led to more tailored and effective treatment plans.

3.3. Management of Cervical Neoplasia in Pregnancy

A specialised MDT approach is crucial in these women due to the clinical rarity and complexity of the condition. The management must reflect a balance between effective oncological treatment and broader maternal care, considering the mother's wishes to continue with the pregnancy and the potential impact of treatment on fetal outcomes. Psychological support is crucial, particularly in cases involving counselling around pregnancy termination [1]. Specialised MDT discussion is therefore essential in ensuring a holistic approach. Management strategies should be individualised and tailored according to the patient's wishes, gestation, maternal age and most importantly the FIGO stage [1]. When the decision is to proceed with a termination, the post-delivery treatment pathway mirrors that of non-pregnant women.

The management of cervical cancer in pregnancy in women considering pregnancy-saving options is summarised in Table 1.

Table 1.

Proposed management of cervical cancer in pregnancy.

Stage	Nodal staging	Under 22 weeks	Nodal staging	22 weeks and above
1A1, no LVSI		Offer conisation(s) via knife or laser cone biopsy from 2nd trimester.		Consider delaying treatment until after delivery.
		Suitable for vaginal delivery		Suitable for vaginal delivery
1A1, LVSI present 1A2 1B1	Positive	Offer termination.		Discuss NACT vs. delaying treatment until delivery⁎
		If declines, consider NACT after 2nd trimester.
	Negative	Delay treatment until delivery⁎
1B2	Positive	Offer termination.		Discuss NACT vs. delaying treatment until delivery⁎
		If declines, discuss NACT after second trimester.
	Negative	Discuss NACT vs. delaying treatment until delivery⁎
1B3 and above		Discuss NACT vs. termination		Discuss NACT vs. delaying treatment until delivery

NACT neoadjuvant chemotherapy.

Adapted from Cervical cancer in pregnancy: diagnosis, staging and treatment [1].

^⁎Delivery includes classical Caesarean section followed by radical hysterectomy bilateral salpingectomy +/− pelvic lymphadenectomy (if not already done).

Pelvic lymphadenectomy for staging is generally safe before 22 weeks [1]. A minimum of 10 lymph nodes is required for adequate staging in pregnancy [17]. Beyond 22 weeks, physiological changes and the growing fetus obstruct the surgical field and make it more challenging to reach this threshold. Between 22 and 25 weeks, lymphadenectomy may be considered depending on the surgeon's expertise and the patient's gestational progress and these cases should be discussed by the MDT [17].

For locally invasive and metastatic cervical cancers (FIGO stages IB3-IVB), gestational age and desire for pregnancy-conservation guide the treatment pathway. For patients not wishing to conserve pregnancy, 12 weeks of gestation serves as a key marker: prior to 12 weeks, primary chemoradiation is preferred; beyond 12 weeks, hysterectomy followed by chemoradiation is preferred.

Neoadjuvant chemotherapy (NACT) is contraindicated in the first trimester due to its teratogenic effects, including interference with organogenesis and a 10–20 % increase in malformation risk [18]. When administered after the first trimester, NACT is relatively safe, with rates of fetal malformations comparable to those of the general population. However, complications such as respiratory distress syndrome and jaundice in the newborn have been reported in some cases. A multicentre cohort study also concluded that NACT was not associated with any significant long-term cognitive or behavioural delay in children exposed in utero [19]. Whilst NACT limits tumour growth, progression risk is not entirely eliminated so close clinical and radiological monitoring is recommended.

Close surveillance is especially crucial in patients who decline treatment. MRI is a valuable tool in pregnancy, allowing tumour monitoring, staging, and complication detection, with minimal harm to fetal development. It has now been deemed an essential part of the management of cervical cancer in pregnancy, enabling swift alteration of plans according to findings. In the third trimester, the focus of cancer management shifts from timely management to delaying cancer treatment whilst accelerating fetal maturation in preparation for delivery. A safe treatment delay time has not yet been established, particularly due to varying tumour progression across individuals. Clinical guidelines recommend discontinuation of NACT 1–3 weeks prior to delivery to minimise maternal risks of excessive haemorrhage and fetal risks of myelosuppression and drug toxicity [18,19].

3.4. Challenges of Radical Hysterectomy in Pregnancy

The standard surgical treatment for cervical cancer is a radical hysterectomy with bilateral pelvic lymphadenectomy, typically indicated for women with localised disease and tumours <4 cm. This procedure entails removal of the cervix, parametrium, paracolpium, uterosacral ligaments, and upper vagina, with extensive dissection of the pelvic sidewall and ureterolysis. In pregnancy, physiological changes such as increased vascularity due to venous congestion and neovascularisation heighten the risk of haemorrhage. Furthermore, the enlarged uterus may limit access to the pelvic sidewall. Prophylactic ligation of the internal iliac arteries may be considered to reduce intraoperative bleeding. Although recent studies suggest simple hysterectomy may be suitable for small-volume disease [20], this approach is less applicable in pregnancy, particularly in the third trimester, where accurate preoperative staging is challenging. The extent of hysterectomy should be guided by multidisciplinary input and clinical expertise, with patients counselled about the potential need for adjuvant chemoradiotherapy. For patients requiring Caesarean section before radical hysterectomy, a classical midline uterine incision is preferred to avoid disruption of the oncological resection plane. A transverse lower segment incision poses a risk of extension into the isthmus, parametria, and paracolpium, increasing operative complexity and bleeding. At early gestations, hysterectomy with fetus in situ carries significant haemorrhagic risk. Surgical termination and cervical dilatation prior to radical hysterectomy are generally avoided due to the risk of bleeding and tumour disruption.

4. Conclusion

Cervical cancer in pregnancy is rare and may mimic typical pregnancy symptoms. All pregnant women with vaginal bleeding should undergo speculum examination, with bimanual assessment if needed. Urgent colposcopy referral (for example, in the UK through the two-week wait pathway) is essential. Multidisciplinary input is critical, with staging (including pelvic lymphadenectomy) generally safe before 22 weeks. Management should be individualised, considering cancer stage, gestation, and patient preferences. Neoadjuvant chemotherapy is contraindicated in the first trimester but may be used safely thereafter. MRI monitoring is important for tracking disease progression and guiding treatment. Further research is needed to establish standardised care guidelines.

Contributors

Katie Crabb contributed to acquiring and interpreting the data and drafting the manuscript, and revising the article critically for important intellectual content.

Janet Okwesa contributed to acquiring and interpreting the data and drafting the manuscript, and revising the article critically for important intellectual content.

Jason KW Yap contributed to patient care, acquiring and interpreting the data, drafting the manuscript and revising the article critically for important intellectual content.

Fong Lien Kwong contributed to patient care, acquiring and interpreting the data, drafting the manuscript and revising the article critically for important intellectual content.

All authors approved the final submitted manuscript.

Patient consent

Written informed consent was obtained from all three patients for publication of their cases and accompanying images.

Provenance and peer review

This article was not commissioned and was peer reviewed. Jason KW Yap, an editorial board member of Case Reports in Women's Health, was not involved in editorial consideration of the manuscript and was blinded to the process.

Funding

This work did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Declaration of competing interest

The authors declare that they have no competing interest regarding the publication of this case series.