Cervical Cancer: 5 Things to Know

Medscape

a day ago

Cervical cancer remains a significant global health concern, ranking as the fourth most common cancer in women worldwide, with an estimated 660,000 new cases and 350,000 deaths in 2022. The burden is unevenly distributed, with over 85% of cases occurring in low- and middle-income countries, where access to preventive care and treatment is limited. In contrast, the incidence and mortality rates in the United States have declined substantially due to widespread implementation of cervical cancer screening programs and human papillomavirus (HPV) vaccination, with an estimated 13,820 new cases and 4,360 deaths expected in the US in 2024.
Cervical cancer develops from a multistep transformation process triggered by persistent infection with high-risk types of HPV, most notably HPV 16 and 18. These oncogenic strains integrate into host DNA, expressing viral proteins E6 and E7, which inactivate the tumor suppressors p53 and retinoblastoma protein (Rb), respectively, and promote genomic instability. The progression from infection to cervical intraepithelial neoplasia and eventually invasive carcinoma may take 15-20 years after initial HPV infection, providing a window for early detection and prevention.
Histologically, the majority of cervical cancers are squamous cell carcinomas (~80%), followed by adenocarcinomas and adenosquamous carcinomas. The World Health Organization now distinguishes between HPV-associated and HPV-independent tumors, with the latter comprising roughly 5% of cases — often displaying worse outcomes and distinct molecular profiles — although current treatment strategies do not yet differ based on HPV status.
Here are five things to know about Cervical Cancer.
1. HPV vaccination and screening remain the most powerful tools for prevention.
Persistent infection with oncogenic HPV types, particularly HPV 16 and 18, is responsible for over 95% of cervical cancers. Screening and vaccination efforts have significantly reduced cervical cancer incidence in countries with established programs.
According to 2018 recommendations from the United States Preventive Services Task Force, women aged 21-29 should undergo cervical cytology (Pap smear) every 3 years, while those aged 30-65 may choose between cytology every 3 years, high-risk HPV testing every 5 years, or cotesting every 5 years.
In contrast, the American Cancer Society's 2020 guidelines recommend beginning screening at age 25 with HPV testing as the preferred method. No routine screening is recommended for women younger than 21, older than 65, or those who have undergone a hysterectomy for benign reasons.
HPV vaccination has transformed cervical cancer prevention. Vaccination before the age of 17 has been shown to reduce cervical cancer incidence by nearly 90%, and growing evidence supports that a single dose may be as effective as a full series, which could simplify implementation in low-resource settings.
2. At-home HPV testing is a breakthrough in improving access.
To expand screening to underserved populations, the FDA approved clinician-supervised self-collected HPV testing in 2024 and fully at-home HPV testing in 2025. These regulatory changes represent a major shift in cervical cancer screening accessibility. Clinical trials have demonstrated that the sensitivity of at-home HPV testing of ~95% is equivalent to that of clinician-collected samples.
This development is especially important for increasing screening rates in medically underserved communities, including individuals with limited access to healthcare, cultural stigma surrounding pelvic exams, or logistical barriers to in-person visits. By reducing these obstacles, at-home HPV testing has the potential to improve early detection, narrow disparities, and prevent progression to advanced cervical cancer among those most at risk.
3. HPV is the primary risk factor, but others contribute to disease development.
While infection with high-risk HPV is a necessary precursor to most cervical cancers, not all women with HPV will develop cancer. Additional factors can influence progression from transient infection to persistent infection, dysplasia, and ultimately malignancy.
Tobacco use is among the most well-established risk factors, doubling the risk of squamous cell carcinoma by impairing local immune defenses in the cervix.
Immunosuppression, especially in individuals with the human immunodeficiency virus, markedly increases the risk of persistent HPV infection and cervical dysplasia.
Other contributing factors include chronic chlamydia infection, long-term use of oral contraceptives, having three or more full-term pregnancies, early age at first childbirth, poor diet lacking in fruits and vegetables, and exposure to diethylstilbestrol in utero. Lower socioeconomic status is consistently associated with higher cervical cancer incidence and worse outcomes, largely due to reduced access to screening and timely care.
Though uncommon, a subset of cervical cancers (3%-8%) are not associated with HPV and tend to present at older ages, potentially with more aggressive biology.
4. Symptoms often appear late, making screening critical.
Most early cervical cancers and pre-cancerous lesions are asymptomatic, which is why regular screening is vital for early detection. When symptoms do occur, they often include abnormal vaginal bleeding, such as post-coital or intermenstrual bleeding, watery or malodorous vaginal discharge, pelvic pain, and dyspareunia. As the disease advances, more severe symptoms may develop, including urinary symptoms, lower abdominal pressure, hematuria, and hematochezia depending on the site of metastasis.
Diagnosis is initiated with colposcopy and biopsy following abnormal screening results. Biopsies may include punch biopsy, endocervical curettage, or cone biopsy depending on lesion size and location.
Once cancer is confirmed, staging typically involves pelvic examination, imaging such as MRI or PET-CT, and sometimes examination under anesthesia. Cervical cancer is staged using the International Federation of Gynecology and Obstetrics system, which incorporates clinical and radiologic findings to guide treatment decisions. Lack of participation in cervical cancer screening is a key reason for late-stage diagnosis, highlighting the critical need to improve screening uptake and address missed opportunities for early detection.
5. Treatment is stage-specific and increasingly personalized.
Treatment of cervical cancer depends on disease stage, type of cervical cancer, patient comorbidities and age, desire for fertility preservation, and whether the cancer has just been diagnosed or has recurred.
For patients with microinvasive disease (stage IA1), options include cold knife conization if the depth of invasion is < 3 mm or total hysterectomy.
Stages IA2-IB2 are typically managed with radical hysterectomy and pelvic lymphadenectomy, although fertility-sparing surgery such as radical trachelectomy may be considered in select patients; intracavitary radiation therapy may be considered as a palliative option for women who are not eligible for surgery or have medical contraindications to other treatments.
Locally advanced disease (stages IB3-IVA) is treated with definitive chemoradiation, usually consisting of external beam radiation therapy combined with weekly cisplatin. Brachytherapy is an essential component of treatment for curative intent. Recent data suggest that induction chemotherapy before chemoradiation may improve survival outcomes in some patients, although this approach is still under investigation.
For recurrent or metastatic disease, systemic therapy with or without palliative radiation is the mainstay. First-line therapy often includes a combination of platinum-based chemotherapy, paclitaxel, and the antiangiogenic agent bevacizumab. For patients with PD-L1-positive tumors, the addition of pembrolizumab, with or without bevacizumab, to chemotherapy has become standard of care based on the KEYNOTE-826 trial. In the second-line setting, options expand to include other cytotoxic agents such as topotecan, gemcitabine, or vinorelbine, as well as immunotherapy and targeted agents.
In pregnancy, treatment strategies depend on cancer stage and gestational age, often balancing maternal prognosis with fetal viability.