A study of the clinico-demographical profile of urinary tract infections in carcinoma cervix

Demography

A total of 187 histologically confirmed cervical cancer patients were studied, out of a total of 218 cervical cancer patients after excluding ineligible cases. The median age was 54 years (interquartile range: 28). Most (70.1%) lived in rural areas and were from low-income households (65.2%) [Table 1].

Urine examination was performed in 151 (80.7%) patients, and 52 (27.8%) had culture-confirmed UTIs [Figure 2]. The majority of infections (78.8%) were detected before commencing cancer treatment [Figure 3]. Pain or dysuria (44.2%), urinary frequency (42.3%), and fever (26.9%) were the most common symptoms. Asymptomatic bacteriuria occurred in 17.3%. Sterile pyuria, defined by elevated white blood cells (10 or more per cubic millimetre) without significant bacterial infection, was found in 8 patients.

Close

Figure 2: Demography of patients. n (number of patients) = 187.

Export to PPT

Close

Figure 3: Temporal association of detection of UTI: Urinary tract infection.

Export to PPT

Univariate analysis

Postmenopausal women faced the highest UTI risk (64.1% vs. 4.7% in premenopausal women; OR = 35.97, p <0.001, phi = 0.640) (Table 2, Figure 4). Albuminuria increased risk to 41.2% (OR = 4.06, p = 0.012, phi = 0.202), and hydronephrosis to 31.1% (OR = 3.11, p = 0.004, phi = 0.209). International Federation of Gynaecology and Obstetrics (FIGO) Stage IIIB was associated with a 32.1% UTI rate (OR = 2.80, p = 0.030), and current smokers had a 50.0% rate (OR = 5.39, p = 0.030). Chronic kidney disease carried a 38.9% risk (OR = 3.67, p = 0.018). Other factors, including glycosuria, ketonuria, hematuria, diabetes, hypertension, obesity, bladder changes, Stage IVA, renal impairment, catheter use, antibiotics, nephrolithiasis, pyometra, uroflow abnormalities, neutropenia, steroid use, and vesicovaginal fistula, showed no significant associations.

Close

Figure 4: Stacked column chart showing risk factors for UTI

Export to PPT

Multivariate logistic regression

It revealed that postmenopausal status was the strongest predictor for the occurrence of UTIs (aOR = 0.015; p < 0.001), implying 66.7-fold higher odds [Table 3]. Glycosuria (aOR = 0.025; p = 0.020) and ketonuria (aOR = 0.016; p = 0.028) conferred 40 and 62.5 fold increased odds, respectively. Albuminuria (aOR = 0.069; p = 0.020) and Stage IIIB disease (aOR = 0.065; p = 0.011) also retained significance. Hydronephrosis and CKD lost significance after adjustment. Excluding hematuria cases for sensitivity analysis did not alter the significance of menopause or glycosuria. Subgroup analyses for steroids and diabetes showed no significance.

Culture and sensitivity

In the culture, positive urine results, Escherichia coli dominated (84.6%), followed by Klebsiella pneumoniae (13.5%), and only one polymicrobial case [Table 4, Figure 5]. Both organisms retained full susceptibility to carbapenems (imipenem and meropenem MIC 0.25 µg/mL; ertapenem MIC 0.5 µg/mL) and aminoglycosides (amikacin MIC 2 µg/mL; gentamicin MIC 1 µg/mL). In contrast, high resistance was noted to co-amoxiclav and ampicillin (MIC 32), fluoroquinolones (MIC 4-16), and piperacillin/tazobactam (MIC 128 for E. coli; intermediate MIC 16 for Klebsiella).

Close

Figure 5: Pie chart showing organisms

Export to PPT

The influence of urinary tract infection in the diagnosis or treatment of cervical cancer

Unilateral or bilateral ureteral obstruction leading to hydronephrosis is a common complication of advanced cervical cancer. The resulting urinary stasis predisposes the patient to recurrent or complicated UTIs (pyelonephritis), which can be a clinical sign of this advanced, obstructive pathology. A severe infection of the upper urinary tract serves as a clinical red flag for potentially undiagnosed advanced cervical cancer, causing ureteral obstruction.^[1]

Mimicry of symptoms

Early-stage cervical cancer is often asymptomatic. When symptoms do appear, they can be easily mistaken for common urogenital conditions like a UTI^[2], which can potentially lead to a delay in definitive diagnosis or misattribution of symptoms. Urinary frequency or urgency is a common and primary symptom of acute cystitis. When observed in the context of persistent vaginal bleeding or discharge, these symptoms warrant a comprehensive gynaecologic evaluation, including a Pap test and colposcopy, to exclude underlying cervical pathology.

Painful urination is the hallmark symptom of lower UTI. In cervical cancer, dysuria can result from inflammatory changes of the adjacent bladder (trigonitis) or direct tumour extension to the bladder (Stage IVA cervical cancer). Therefore, persistence of dysuria despite appropriate antibiotic therapy should prompt further investigation.^[3]

Pelvic discomfort or pain can be present in severe UTIs or pelvic inflammatory disease, as well as advanced cervical cancer with involvement of the parametrium. Persistent or non-specific pelvic pain requires ruling out gynecologic malignancy, even if an initial workup suggests a UTI.^[2]

Abnormal vaginal discharge in cervical cancer can be mistaken for discharge associated with severe vaginitis (e.g., bacterial vaginosis or candidiasis). While a UTI itself does not cause abnormal vaginal discharge, the proximity of the urogenital tracts means discharge, especially if watery, bloody, or foul-smelling, may be incorrectly attributed to an infectious process rather than a friable tumour.

Magnitude of the problem

Research shows that urinary tract infections (UTIs) are common in patients with solid tumours, especially those arising from the pelvis. Recurrent UTIs occur mostly in bladder tumour patients.^[3]

UTIs represent a significant comorbidity in cervical cancer patients.^[4] 12.5 to 43.1% of urine samples collected from cervical cancer patients showed significant bacterial growth in different studies.^[5,6] However, the exact incidence varies based on cancer stage and individual factors.^[5]

Age,^[7] urolithiasis (19.6%),^[4] immunosuppressive therapy,^[6] and diabetes mellitus (23.9%)^[4,7] are commonly recognised causes of UTI in cervical cancer. 26% of infections are linked to febrile neutropenia.^[4] Apart from causing UTI, diabetes mellitus (DM),^[8] often associated with obesity,^[9] also modifies the outcome of cervical adenocarcinoma. Some studies reveal that diabetes in postmenopausal women may even increase the risk of cervical cancer.^[10]

Invasive surgery^[6] is an important cause of UTI in cervical cancer patients. After radical surgery, common issues include weak bladder contractions, overactive bladder, incontinence, low bladder compliance, fistulas, and hydronephrosis. Nerve-sparing surgery has helped reduce these bladder problems.^[11] Duration of surgery, blood loss, catheterisation time, and urinary retention are independent risk factors in cervical cancer patients for the causation of UTIs,^[7] especially after radical hysterectomy. Catheter-associated UTIs are more common, particularly in current smokers and those with prolonged catheter use.^[5,12] A nomogram model was created by Zou et al. using multivariate analysis to predict the risk of developing catheter-associated UTIs, who found that the duration of urinary catheterisation, presence of urinary leukocyte esterase, and positive urine culture were independent risk factors for catheter-associated UTIs after radical hysterectomy for cervical cancer.^[13]

Patients during chemotherapy (82.6%)^[4] and radiotherapy^[14] are at higher risk of UTIs. UTIs are more common in stage III cervical cancer patients (33.3%) compared to stage II (16.7%) during radiotherapy.^[14] Better technology, such as conformal radiotherapy, has reduced these complications.^[11] However, the study by Prasad et al. revealed that half of the patients undergoing external pelvic radiotherapy experience recurrent infections despite appropriate antibiotic therapy. This study highlighted the need for regular mid-stream screening in gynaecological cancer patients during radiotherapy for timely diagnosis and antibiotic treatment to prevent further damage to the already vulnerable uroepithelium caused by radiation.^[14]

E. coli is the most common organism isolated in cancer patients with UTI (40%).^[15] In cervical cancer patients, the incidence of Escherichia coli (35.9%) infection is followed by Klebsiella. These are also the most common causes of UTIs after radical surgery for cervical cancer.^[6,7] Polymicrobial UTIs are observed in 15% (7 patients).^[4] Staphylococcus aureus is the most common Gram-positive bacterium, found four times more than coagulase-negative staphylococci.^[6]

A study of resistance patterns to common antibiotics reveals that Escherichia coli showed resistance to cefotaxime in 25% of cases and ciprofloxacin in 39.3%.^[4] Most bacterial isolates were resistant to ampicillin, followed by cotrimoxazole and cefixime. Polymyxin B and imipenem are the most effective against Gram-negative bacteria. Vancomycin and azithromycin are most effective against Gram-positive bacteria.^[6]

Complications

Complications of urinary tract infection in cervical cancer patients have been highlighted in different studies. A few studies indicate that urinary tract infection might even increase the incidence of urothelial malignancies.^[16] Long-term urological complications, such as ureteral stricture and resultant hydronephrosis, are known sequelae of radiotherapy. Patients with chronic ureteral stents placed for obstruction relief have a higher rate of recurrent UTIs and subsequent pain, requiring multiple procedures for management over time.^[17] Severe or recurrent UTIs, especially those that progress to pyelonephritis, can lead to treatment intolerance or the need to discontinue or delay scheduled radiation or concurrent chemotherapy, potentially compromising the therapeutic efficacy and overall prognosis.^[18] The occurrence of a severe, complicated UTI or a late-onset infection associated with a urological complication (like stricture or stent) is a significant morbidity event, impacting quality of life and increasing the risk of death, especially if the infectious organism is multidrug-resistant.^[18]

Comparison of the current study results with existing literature

The prevalence of UTI of 27.8% in the current study falls within the range (12.5-43.1%) reported by previous studies. Unlike others, who observed peaks during chemotherapy (82.6%), we detected most infections before treatment.

Escherichia coli represented 84.6% of isolates in our cohort, well above what has been noted elsewhere, while Klebsiella rates were comparable. Local microbial ecology, antibiotic-use patterns, and strict culture criteria (≥10⁵ CFU/mL) may account for this difference. We found postmenopausal status, FIGO Stage IIIB, albuminuria, glycosuria, and ketonuria to be significant UTI predictors. In contrast, other studies highlighted diabetes, urolithiasis, and immunosuppression as predictors likely reflecting different patient mixes.

Earlier work reported cefotaxime resistance (25%) and ciprofloxacin resistance (39.3%), with polymyxin B and imipenem being most effective. Our isolates were uniformly susceptible to aminoglycosides but showed high resistance to beta-lactams in addition to quinolones, except levofloxacin. Nitrofurantoin, fosfomycin, and trimethoprimsulfamethoxazole are effective oral therapies for E. coli UTIs, but are unreliable against Klebsiella. These differences might highlight variations in socioeconomic factors or prescribing differences.

How our findings help

Our study emphasises the need for routine pre-treatment urine culture in cervical cancer patients. Recognising high-risk factors, as determined in our study, can help prioritise monitoring in these vulnerable subgroups. Local culture sensitivity patterns can help in selecting effective empiric antibiotics while awaiting culture results.

Limitations

This single-centre, cross-sectional study is limited by small subgroup sizes (e.g., diabetics, immunosuppressed) and a lack of follow-up data on recurrence or post-therapy infections. Potential residual confounders may exist from unmeasured variables. Thus, generalizability may be restricted except in the need for pre-treatment detection of infections. As a continuation of this study, we plan a community-based study examining social and hygiene practices, such as bathing water quality, toilet type, and sanitary pad use, to better understand risk factors for UTI in cervical cancer patients.