​​​​​​​Updated May 2026

HPV-associated Invasive Squamous Cell Carcinoma & Adenocarcinoma

A. Stage IA – IB1

The treatment of these lesions will be based on a thorough histologic examination of a properly obtained cone biopsy (LEEP) specimen or directed biopsy if the lesion size is not amenable to LEEP, physical exam, and recommended staging investigations (see Section 4). It is strongly recommended that all patients have their slides reviewed at BC Cancer and that the patient is presented to the multidisciplinary conference for treatment recommendations.

B. Stage IA1 without LVI

Management of HPV-associated Stage IA1 cervical cancers with no lymph-vascular space invasion (LVI/LVSI) may occur in the community setting. If margins are negative, conservative treatment with simple hysterectomy and bilateral salpingectomy is recommended. If margins are positive, a repeat LEEP to obtained clear margins is recommended followed by a simple hysterectomy and bilateral salpingectomy. If unable to obtain negative margins, referral to Gynecologic Oncology for management is indicated.

For very early disease removed with a satisfactory margin, cold knife conization or LEEP may be considered adequate therapy, if fertility preservation is desired. Review with Gynecologic Oncology is strongly recommended.

C. Stage IA1 with LVI, Stage IA2, Stage IB1

All patients with Stage IA1 with LVSI and greater should be referred to Gynecologic Oncology for management. For patients with Stage IA1 lesions with LVSI, IA2, or IB1 disease measuring ≤2 cm with <10 mm stromal invasion on histopathology (or <50% cervical stromal invasion on MRI), negative nodes, and negative or close margins, simple hysterectomy with pelvic lymph node assessment (sentinel lymph node biopsy or pelvic lymphadenectomy) may be considered appropriate. The SHAPE trial supports this approach, demonstrating non-inferior oncologic outcomes compared to radical hysterectomy, with significantly lower morbidity, particularly urinary and sexual dysfunction1.

For Stage IA1 lesions with LVSI, IA2, or IB1 with positive margins, one repeat LEEP to obtain clear margins is recommended followed by simple hysterectomy, bilateral salpingectomy, and nodal assessment. If it cannot be defi​nitively demonstrated that the cervical lesion meets SHAPE criteria (≤2cm, <10mm stromal invasion or <50% cervical stromal invasion on MRI) then radical surgery (as per Stage IB2/IIA1) should be performed. If a repeat LEEP cannot be performed, an MRI with no evidence of residual disease in an acceptable option

Fertility sparing treatment

Fertility-sparing surgery may be considered in carefully selected patients with HPV associated Stage IA2–IB1 cervical cancer who have a strong desire to preserve fertility. For Stage IA2 disease or IB1 tumours <2 cm with no LVSI, conization or simple trachelectomy with negative margins and sentinel lymph node biopsy may be sufficient, particularly when the depth of invasion is minimal^1-3. For patients with tumours ≥2 cm, deeper stromal invasion, or presence of LVSI, radical trachelectomy with pelvic lymph node assessment remains the preferred approach and can be performed via vaginal, laparoscopic, or abdominal route depending on tumour characteristics and surgeon expertise⁴. MRI should be used preoperatively to confirm tumour size and absence of parametrial invasion. Caution should be exercised in larger adenocarcinomas, due to the increased likelihood of skip lesions / residual disease with conservative management. Neoadjuvant chemotherapy is listed in international guidelines as on option prior to fertility sparing surgery to shrink tumour volumes and increase the potential of achieving adequate margins; however, prospective evidence is lacking ⁵. Multidisciplinary evaluation is essential, and patients should be counselled on the potential risks of recurrence, obstetric complications, and the need for close follow-up.

Role of sentinel lymph node biopsy for stage IA1 with LVSI - IB2

Sentinel lymph node mapping can increase the detection of metastatic lymph nodes over conventional lymphadenectomy, as mapping studies have shown that up to 10% of sentinel nodes are found in areas not captured in a standard pelvic lymph node dissection⁶. In addition, diagnostic accuracy is increased with the use of pathological ultra-staging for the sentinel node.

Appropriate candidates for sentinel lymph node biopsies in lieu of pelvic lymphadenectomy include patients who meet all the following criteria:

1. Tumour diameter less than 4cm
2. No suspicious lymph nodes seen on pre-operative imaging or during surgery
3. Bilateral sentinel lymph node detected intra operatively

If a sentinel lymph node is not identified intraoperatively, a full pelvic lymph node dissection should be performed in that hemipelvis. Patients who do not meet the above-mentioned criteria for sentinel lymph node biopsy should have a full bilateral pelvic lymphadenectomy.

When used appropriately, the sensitivity of a sentinel node biopsy has been reported to be 99.6% with a negative predictive value of 99.9%⁷.

Minimally invasive surgery (MIS) for hysterectomy in early-stage cervical cancer

Minimally invasive radical hysterectomy is not routinely recommended for Stage IA2–IB1 cervical cancer due to inferior survival outcomes compared to open surgery^7,8. However, MIS may be considered in highly selected low-risk patients if all the following criteria are met^1,2,4,9-11:

• Tumour <2 cm
• LEEP or cone-biopsy with negative margin (no residual tumour)
• Superficial stromal invasion (<10mm)
• Negative nodal assessment preoperatively and intraoperatively
• Performed by experienced surgeons in high-volume centres
• Patient is appropriately counselled on risks and alternatives
• Consider use of protective technique (no uterine manipulator).

Open surgery is recommended if any of the following are present:

• Tumour ≥2 cm or residual disease on exam/imaging
• Positive margin after diagnostic excision
• Deep stromal invasion
• Suspicious lymph nodes
• Inability to meet protective surgical criteria

Adjuvant radiotherapy

Adjuvant pelvic radiotherapy may be recommended when simple hysterectomy is inadvertently performed where modified radical hysterectomy and pelvic lymph node dissection (or sentinel lymph node biopsy) was indicated for treatment of the invasive disease based on risk factors such as stage, LVSI, and margin status. Completion of radical hysterectomy post-radiation is not routinely recommended but can be discussed in multidisciplinary conference.

Postoperative radiotherapy will also be recommended following radical hysterectomy in the face of poor prognostic factors (see below).

D.  Stage IB2 and IIA1

For HPV associated cancers, we recommend either radical surgery or primary chemoradiotherapy after multidisciplinary assessment and consultation.

Radical surgery

Open radical surgical approach is required, including modifi​ed radical hysterectomy with pelvic lymph node dissection (or sentinel lymph node biopsy). If the patient is not a surgical candidate, then radical radiotherapy would be used with a combination of external beam treatment plus intracavitary/interstitial brachytherapy.

Radical surgery may be considered as primary therapy in the following situations:

• Contraindications to primary radiation therapy
• Suitable surgical and anesthetic risk
• High likelihood of complete resection with adequate margins
• HPV independent squamous cell or adenocarcinoma

Patients not fulfi​lling these criteria will be treated with primary chemoradiotherapy.

Adjuvant radiotherapy

Adjuvant pelvic radiotherapy is recommended if per Sedlis Criteria as outlined below¹²:

Adjuvant concurrent chemoradiotherapy

Adjuvant pelvic radiotherapy with concurrent chemotherapy is recommended if any of the following is identifi​ed on pathology¹³:

• Positive pelvic lymph node
• Positive parametrial involvement
• Positive margins

The addition of vaginal vault brachytherapy can be considered in the case of a positive vaginal mucosal margin. With the presence of suspected residual vaginal disease, brachytherapy boost should be used following adjuvant chemoradiation.

E. Stage IB3, IIA2, IIB, III, or IV

Concurrent chemoradiotherapy with external beam radiation treatment followed by high-dose rate (HDR) image-guided brachytherapy is recommended standard of care with additional therapy options discussed and recommended as appropriate (see Chemotherapy and Radiotherapy sections below). If there is evidence of residual disease with positive pathology at least 3 months after completion of radiotherapy, salvage hysterectomy may be considered. These cases should be presented at multidisciplinary conference.

Radiotherapy can be used for palliation and local-regional control in the metastatic setting. Palliative chemotherapy can be considered (see below).

​HPV-independent squamous cell/adenocarcinoma

HPV-independent cervical adenocarcinomas and squamous cell carcinomas are biologically distinct entities associated with older age at diagnosis, advanced stage, and significantly worse prognosis. In retrospective analyses, these tumours exhibit poor response to standard chemoradiotherapy and have higher recurrence rates¹⁴.  HPV independent carcinoma cases should be reviewed in multidisciplinary conference.

For early-stage disease, radical hysterectomy with lymph node dissection is recommended. Fertility-sparing procedures are not advised. Extended staging procedures such as omentectomy may be considered.

In locally advanced disease, concurrent chemoradiotherapy remains standard, but careful response monitoring is essential given poor response rates. Early salvage surgery should be considered in cases with incomplete response. Additional biomarker testing may be considered to identify potential candidates for immune checkpoint inhibitors (PD-L1 CPS score IHC) or anti-HER2 targeted therapies (HER2 IHC). Clinical trial enrolment should be encouraged in this setting.​